Close Window
Aetna Aetna
Clinical Policy Bulletin:
Alemtuzumab (Campath)
Number: 0764


Aetna considers alemtuzumab (Campath) medically necessary for the treatment of any of the following conditions:

  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) including T-cell prolymphocytic leukemia; or 
  • Treatment of mycosis fungoides or Sezary syndrome with histologic evidence of large cell transformation and aggressive growth rate in non-candidates for transplant
  • Second-line therapy for individuals with stage III mycosis fungoides or Sezary syndrome that is refractory to or progressive following initial treatment options; or
  • Second-line therapy for relapsed or refractory angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, or anaplastic large cell lymphoma, or enteropathy-associated T-cell lymphoma in in non-candidates for high-dose therapy with autologous stem cell rescue; or
  • Adult T-cell leukemia/lymphoma in nonresponders to first-line therapy for acute disease or lymphoma in noncandidates for transplant; or
  • Single-agent therapy for relapsed or refractory primary cutaneous anaplastic large cell lymphoma (ALCL); or
  • T-cell prolymphocytic leukemia, as primary treatment for symptomatic disease or salvage/second-line therapy; or
  • T-cell large granular lymphocytic leukemia, second-line therapy for persons with progressive or refractory disease; or
  • Single agent salvage therapy for Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma that does not respond to primary therapy or for progressive or relapsed disease.

Aetna considers alemtuzumab experimental and investigational for the following indications (not an all-inclusive list) because its effectiveness for these indications has not been established:

  • Acute lymphoblastic leukemia
  • Aplastic anemia
  • Arthritis
  • Autoimmune cytopenias
  • Eosinophilic myeloid disorders/eosinophilic diseases
  • Graft-versus-host disease
  • Guillain-Barre syndrome
  • Histiocytic sarcoma
  • Multiple sclerosis
  • Myelodysplastic syndrome
  • Polyradiculoneuropathies (e.g., Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy)
  • Pure red cell aplasia
  • Scleroderma/systemic sclerosis
  • Severe combined immunodeficiency
  • Solid organ transplantation
  • Sporadic inclusion body myositis
  • Vasculitis.


Alemtuzumab (Campath) is a recombinant DNA-derived, humanized monoclonal antibody.  It is directed against a small (21 to 28 kD) glycosylphosphatidylinositol-anchored glycoprotein, CD52, which is expressed on the surface of normal as well as malignant B- and T-lymphocytes, natural killer cells, monocytes, macrophages, but not on hematopoietic progenitor cells.  Thus, alemtuzumab has a potential broad application across a spectrum of B- and T-cell malignancies.  The proposed mechanism of action for alemtuzumab is antibody-dependent lysis of leukemic cells following cell surface binding.

In a retrospective study, Fiegl et al (2006) evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated chronic lymphocytic leukemia (CLL) who received treatment in the routine clinical setting.  Data were collected from 115 consecutive subjects who received alemtuzumab therapy at 25 participating centers in Austria.  Patients received a median of 3 prior lines of therapy (range of 1 to 11), and 59 % had fludarabine-refractory disease.  Alemtuzumab was administered intravenously or subcutaneously with a planned schedule of 30 mg 3 times per week for up to 12 weeks.  Patients received valacyclovir and trimethoprim/sulfamethoxazole for anti-infective prophylaxis.  The overall response rate was 23 %, with complete responses achieved in 5 % of patients.  Stable disease (SD) was achieved in 36 % of patients.  After a median follow-up of 17.5 months, the median overall survival (OS) was 20.2 months for all patients.  A multi-variate Cox regression analysis that included pre-treatment baseline characteristics, response to therapy, and cumulative dose of alemtuzumab indicated that bulky lymphadenopathy, the administration of greater than or equal to 3 previous therapies, and lack of response to alemtuzumab remained significant independent risk factors for inferior OS.  The median OS had not been reached for responding patients.  The median OS was 29.5 months for patients with SD and 10.8 months for patients with progressive disease (PD).  The authors concluded that the broad use of alemtuzumab in the routine clinical practice setting is feasible and active in unselected patients with pre-treated CLL, and the current results confirmed the activity and safety of this agent, as reported in previously published clinical studies.

Alemtuzumab initially received accelerated approval in 2001 from the U.S. Food and Drug Administration (FDA) for the treatment of fludarabine-refractory CLL.  Additional clinical data were required to confirm its benefit in this setting and in patients previously untreated.  On September 19, 2007, the FDA expanded the labeling and granted regular approval for single-agent alemtuzumab for the treatment of B-cell CLL (B-CLL).  This was achieved in part via an open-label, randomized study, which demonstrated the benefits of first-line use of alemtuzumab (NCI, 2007; Demko et al, 2008).

Hillmen and co-workers (2007) performed a randomized trial to assess the safety and effectiveness of intravenous alemtuzumab compared with chlorambucil in first-line treatment of CLL.  Patients received alemtuzumab (30 mg 3 times per week, for up to 12 weeks) or chlorambucil (40 mg/m(2) every 28 days, for up to 12 months).  The primary end point was progression-free survival (PFS).  Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and OS.  A total of 297 patients were randomly assigned to receive alemtuzumab (n = 149) or chlorambucil (n = 148).  Alemtuzumab-treated subjects had superior PFS, with a 42 % reduction in risk of progression or death (hazard ratio [HR] = 0.58; p = 0.0001), and a median time to alternative treatment of 23.3 months versus 14.7 months for chlorambucil-treated subjects (HR = 0.54; p = 0.0001).  The ORR was 83 % with the alemtuzumab group (24 % CR) versus 55 % with the chlorambucil group (2 % CR); differences in ORR and CR were highly significant (p < 0.0001).  Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil.  Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil.  Cytomegalovirus events had no apparent impact on effectiveness.  The authors concluded that as first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease-negative remissions compared with chlorambucil, with predictable and manageable toxicity.

Besides its use in the treatment of CLL and other lymphoid neoplasms, alemtuzumab has also been studied as an immunosuppressive agent in bone marrow/solid organ transplantation and in the treatment of autoimmune disorders including arthritis, autoimmune cytopenias, multiple sclerosis (MS), and vasculitis (Reiff, 2005; Lee and D'Cruz, 2008).  However, its clinical value for these indications has not been established.

In a phase II study, Kennedy and associates (2003) assessed the safety, tolerability and effectiveness of alemtuzumab in patients with relapsed or refractory advanced stage cutaneous T-cell lymphoma (CTCL).  A total of 8 patients were enrolled, 7 with mycosis fungoides/Sezary syndrome (MF/SS) and 1 with large-cell transformation of MF.  Seven patients had disease refractory to multiple previous therapies.  Alemtuzumab (30 mg) was administered intravenously 3 times per week for 12 weeks or until maximum response.  The ORR was 38 %, with 3 patients achieving partial remission (PR), 2 patients with SD and 3 patients with PD during treatment.  The time to progression was short, with all patients developing PD within 4 months of starting alemtuzumab.  Response duration in the 3 PR patients was also brief, with responses lasting less than 3 months in all 3 cases.  Significant hematological and immunosuppressive toxicity was observed, with both grade 3 to 4 cytopenias and significant infectious complications occurring in a majority of cases.  The authors concluded that these findings suggested that in heavily pre-treated, refractory, advanced stage MF/SS, although alemtuzumab has biological activity, it is associated with significant toxicity and only modest clinical utility.  As such, combination regimens incorporating alemtuzumab merit further investigation in this difficult to treat patient group.
In another phase II study, Lundin and co-workers (2003) evaluated the safety and effectiveness of alemtuzumab in 22 patients with advanced MF/SS.  Most patients had stage III or IV disease, reduced performance status, and severe itching.  The ORR rate was 55 %, with 32 % of patients in CR and 23 % in PR.  Sezary cells were cleared from the blood in 6 of 7 (86 %) patients, and CR in lymph nodes was observed in 6 of 11 (55 %) patients.  The effect was better on erythroderma (ORR, 69 %) than on plaque or skin tumors (ORR, 40 %) and in patients who had received 1 to 2 previous regimens (ORR, 80 %) than in those who had received 3 or more prior regimens (ORR, 33 %).  Itching, self-assessed on a 0 to 10 visual analog scale, was reduced from a median of 8 before treatment to 2 at the end of therapy.  Median time to treatment failure was 12 months (range of 5 to 32+ months).  Cytomegalovirus re-activation (causing fever without pneumonitis and responding to ganciclovir) occurred in 4 (18 %) patients.  Six additional patients had suspect or manifest infection (fever of unknown origin, n = 3; generalized herpes simplex, n = 1; fatal aspergillosis, n = 1).  One patient had fatal mycobacterium pneumonia at 10+ months.  All serious infectious adverse events (except CMV) occurred in patients who had received 3 or more prior regimens.  Progression of squamous cell skin carcinoma was noted in 1 patient.  The authors noted that alemtuzumab shows promising clinical activity and an acceptable safety profile in patients with advanced MF/SS, particularly in patients with erythroderma and severe itching and those who were not heavily pre-treated. 

Capalbo et al (2003) reported the use of alemtuzumab as salvage treatment in 3 patients with advanced MF/SS who had previously been treated with conventional chemotherapy.  Two patients (case 1 and case 2), aged 42 and 68 years, respectively, were heavily pre-treated (more than 3 prior therapy regimens, including autologous transplantation in case 2) and refractory to conventional chemotherapy, and the 3rd patient (case 3), aged 80 years, who had refused any chemotherapy, had been resistant to treatment with cyclosporine and steroids.  Alemtuzumab was administered intravenously, after an escalating dose from 3 to 10 mg, at the dose of 30 mg, 3 times weekly, to a total dose of 1080, 223, and 480 mg, respectively.  The patients with SS (case 2 and case 3) showed clearance of circulating Sezary cells and clinical improvement of the skin lesions after 2 weeks of treatment.  Two patients (case 1 and case 3) completed the treatment (12 and 6 weeks) without significant toxicity, the former achieving a PR and the latter a clinical CR.  The patient (case 2) who suffered from ischemic cardiopathy and diabetes quickly achieved clinical improvement of the SS, but he died because of a myocardial infarction after 3 week of treatment.  This report showed that the treatment with alemtuzumab is active even in patients with advanced refractory MF/SS.  The authors concluded that further clinical observations on a larger cohort of patients are needed to establish if alemtuzumab may have a role as first-line therapy in addition to conventional therapy including chemotherapy.

The National Comprehensive Cancer Network (NCCN)'s Drugs & Biologics Compendium (2010) includes indications for alemtuzumab in chronic lymphocytic leukemia/small lymphocytic lymphoma as a fist-line therapy for stage II-IV disease. Alemtuzumab is also indicated for patients with CLL with del(17p) with greater than 20 % cells who have non-bulky adenopathy and partial response following allogeneic stem cell transplant, for patients with CLL without del(17p) who have relapsed or refractory disease following a long response (more than 3 years) to first-line therapy, for relapsed or refractory CLL without del(17p) in patients with a short response (less than 2 years) who are less than age 70 years or in older patients without significant comorbidities, and for relapsed or refractory CLL with del(17p) with greater than 20 % cells.  National Comprehensive Cancer Network guidelines (2010) also recommend use of alemtuzumab in combination with fudarabine or rituximab for relapsed or refractory CLL without del(17p) in patients with a short response (less than 2 years) who are less than age 70 years or in older patients without significant co-morbidities; as a component of CFAR (cyclophosphamide, fludarabine, alemtuzumab, and rituximab) regimen as first-line therapy for state II-IV CLL with del(17p) with greater than 20 % cells; with rituximab or as a component of CFAR regimen for relapsed or refractory CLL with del(17p) with greater than 20 % cells.

Aleumtuzumab is recommended by NCCN (2012) as second-line therapy for patients with stage III mycosis fungoides or Sezary syndrome that is refractory to or progressive following initial treatment. It is also indicated for treatment of mycosis fungoides or Sezary syndrome with histologic evidence of large cell transformation and aggressive growth rate in noncandidates for transplant.

Regarding use in peripheral T-cell lymphomas, alemtuzumab is recommended as second-line therapy for relapsed or refractory angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, or anaplastic large cell lymphoma in non-candidates for high-dose therapy with autologous stem cell rescue (NCCN, 2010).

NCCN guidelines (2010) also recommend alemtuzumab for use in Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma, as a single-agent salvage therapy for disease that does not respond to primary therapy or for progressive or relapsed disease.

Muraro and Bielekova (2007) reviewed the mechanism(s) of action as well as safety and effectiveness of some of the most promising new therapeutic strategies for MS.  Fingolimod (FTY720) is a novel oral immunomodulating agent that acts through preventing lymphocyte re-circulation from lymphoid organs.  Monoclonal antibody therapy has provided investigators the opportunity to rationally direct the therapeutic intervention against specific molecules.  Targeting molecules of the immune system such as CD52 (alemtuzumab), CD25 (daclizumab), VLA-4 (natalizumab) and CD20 (rituximab) have resulted in potent immunomodulatory effects through sometimes unpredicted mechanisms.  The potential of immunoglobulins to induce re-myelination in the central nervous system is being investigated in an attempt to develop therapies promoting tissue repair and functional recovery.  The evidence supporting the potential of these emerging immunotherapies suggested that strong progress is being made in the development of effective cures for MS.  Waubant (2007) noted that there are several phase III clinical trials in relapsing-remitting MS with promising agents, including intravenous agents administered once- or twice-yearly (alemtuzumab, rituximab) and oral agents (FTY720, fumaric acid, laquinomod).

Lee and D'Cruz (2008) reviewed novel therapies for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitides (AAV).  Tumour necrosis factor (TNF)-alpha antagonism with infliximab has been described favourably in retrospective series and open-label trials.  However, evidence from the WGET (Wegener's Granulomatosis Etanercept Trial) does not support the clinical use of etanercept, and a significantly higher malignancy rate following TNF-alpha inhibition questions the role of this approach.  Uncontrolled evidence alone supports remission induction with rituximab-mediated B-cell depletion and may be less effective in predominantly granulomatous AAV.  Remission following T-cell depletion can be achieved with alemtuzumab and ATG, but it is unclear what the clinical role will be for these agents in AAV.  In addition, these agents are associated with prolonged lymphopenia and pulmonary complications, respectively.  Stem cell transplantation to support immune reconstitution following the use of such agents has been studied in AAV, but trials included very few patients.

Alemtuzumab has been examined for use in allogeneic organ transplantation.  While recent studies demonstrated a conspicuous effect of alemtuzumab on peripheral dendritic cells (DC) in clinical graft-versus-host disease (GVHD), its effectiveness in patients receiving allogeneic organ transplants is still undefined.  Kirsch and colleagues (2006) evaluated the peripheral DC repertoire in kidney transplant recipients after either alemtuzumab induction therapy followed by FK506 monotherapy or after conventional immunosuppression (FK506, mycophenolate mofetil and steroids) without any induction agent.  Induction with alemtuzumab caused a strong and sustained reduction of the total number of peripheral DC and a significant shift from myeloid to plasmacytoid DC subsets (mDC/pDC ratio) as early as 1 month post-transplantation.  These data showed that alemtuzumab induction targets the peripheral DC repertoire, which might add another mechanism allowing immunosuppressive drug minimization.  The authors stated that more studies are needed to further elucidate the functional significance of these finding in the setting of allogeneic organ transplantation.

In a phase II clinical trial, Martinez et al (2009) examined the safety and effectiveness of alemtuzumab in treating steroid-refractory acute GVHD (aGVHD) grade II or higher after stem cell transplantation.  A total of 10 adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study.  Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement.  Five patients responded to treatment, 2 with CR and 3 with partial response.  Eight infectious events (4 of grade 3 to 4) and 7 CMV re-activations were observed.  Six patients had grade 3 to 4 cytopenia.  All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range of 4 to 88 days) after alemtuzumab treatment.  Overall, these findings suggested that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.

Huang et al (2007) noted that the use of alemtuzumab for induction therapy in kidney transplantation has been increasing.  These researchers presented a report of graft outcomes associated with alemtuzumab induction from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database.  A total of 14,362 deceased donor kidney transplants from 2003 to 2004 received no induction (n = 4,364), anti-thymocyte globulin (ATG; n = 4,930), interleukin-2 receptor antagonists (IL-2RA; n = 4,378), or alemtuzumab (n = 690).  Acute rejection (AR) within the initial hospitalization, 6 months, and 1 year; graft survival; and rejection-free survival were examined.  Graft and rejection-free survival of alemtuzumab recipients maintained with tacrolimus (FK) or cyclosporine (CSA), mycophenolate mofetil (MMF), and steroids versus no calcineurin inhibitors (CNI), MMF, and steroids were compared.  Alemtuzumab recipients had less AR during the initial hospitalization (2.3 %) than no induction, ATG, and IL-2RA (7.6 %, 3.4 %, and 4.8 %, respectively; p < 0.001).  There was increased AR at 6 months and 1 year with alemtuzumab (14.5 % and 19.2 %, respectively) compared to no induction (12.7 % and 14.8 %, p < 0.001), ATG (8.2 % and 10.2 %, p < 0.001), and IL-2RA (11.1 % and 13.0 %, p < 0.001) with no difference in adjusted relative risk for graft loss.  Alemtuzumab recipients receiving FK or CSA, MMF, and steroids had increased graft (FK/MMF/steroids, p < 0.001, CSA/MMF/steroids, p = 0.007) and rejection-free survival (FK/MMF/steroids, p < 0.001, CSA/MMF/steroids, p = 0.006) over 24 months compared to no CNI, MMF, and steroids.  The authors concluded that despite reduced early rejection, AR rates at 6 months and 1 year with alemtuzumab induction exceeded other forms of induction therapy.  Maintenance with CNI-based immunosuppression may improve graft and rejection-free survival compared to CNI-free regimens among alemtuzumab recipients.

Reams et al (2007) noted that despite substantial improvements in early survival after lung transplantation, refractory acute rejection (RAR) and bronchiolitis obliterans syndrome (BOS) remain major contributors to transplant-related morbidity and mortality.  These investigators examined the effectiveness of alemtuzumab in the treatment of RAR (n = 12) and BOS (n = 10) after human lung transplantation.  All patients failed conventional treatment with methylprednisolone and ATG and received strict infection prophylaxis.  Alemtuzumab significantly improved histological rejection scores in RAR.  Total rejection grade/biopsy was 1.98 +/- 0.25 preceding alemtuzumab versus 0.33 +/- 0.14 post-treatment, p < 0.0001 (with a similar number of biopsies/patient per respective time interval).  Freedom from BOS was observed in 65 % of RAR patients 2 years after alemtuzumab treatment.  Although there was no statistically significant change in forced expiratory volume in 1 second (FEV1) before and after alemtuzumab treatment in patients with BOS, a stabilization or improvement in BOS grade occurred in 70 % of patients.  Patient survival 2 years after alemtuzumab for BOS was 69 %.  Despite a dramatic decline in CD4 counts in alemtuzumab-treated patients, only 1 patient developed a lethal infection.  Thus, these findings provided the first evidence that alemtuzumab is a potentially useful therapy in lung transplant recipients with RAR or BOS.

Ciancio and Burke (2008) noted that kidney transplantation has become the treatment of choice for both the quality of life and survival in patients with end-stage renal disease (ESRD).  However, the immunosuppressive regimen that allows optimal kidney transplant outcome remains elusive.  One of the more promising induction agents, alemtuzumab, was introduced to kidney transplantation by Calne in the late 1990s with low dose cyclosporine A monotherapy, with the hope of establishing "prope" or near tolerance.  Subsequent pilot studies with alemtuzumab alone or monotherapy (DSG, Rapa) demonstrated high rates of AR along with occasional humoral components that lead to abandoning the concept of alemtuzumab as a "magic bullet" to achieve tolerance, "prope" or otherwise.  Many programs have since modified maintenance immunosuppression using low dose tacrolimus, and shown acceptable rates of AR, with relatively low incidence of viral infection and lympho-proliferative disorders along with cost benefit.  However, there are only 3 prospective, randomized studies, which are small with 1 year or less follow-up, and most published series utilized historical control groups with relatively short follow-up.  The authors stated that since extrapolation from short-term data is far from secure, long-term, prospective, randomized studies with alemtuzumab are needed to ascertain the optimal immunosuppressive regimen.

Shapiro et al (2007) employed antibody pre-conditioning with alemtuzumab and post-transplant immunosuppression with low-dose tacrolimus monotherapy in 26 consecutive pediatric kidney transplant recipients.  Mean recipient age was 10.7 +/- 5.8 years, 7.7 % were undergoing re-transplantation, and 3.8 % were sensitized, with a panel reactive antibody greater than 20 %.  Mean donor age was 32.8 +/- 9.2 years.  Living donors were utilized in 65 % of the transplants.  Mean cold ischemia time was 27.6 +/- 6.4 hours.  The mean number of HLA mismatches was 3.3 +/- 1.3.  Mean follow-up was 25 +/- 8 months.  One- and 2-year patient survival was 100 % and 96 %, respectively.  One- and 2-year graft survival was 96 % and 88 %, respectively.  Mean serum creatinine was 1.1 +/- 0.6 mg/dL, and calculated creatinine clearance was 82.3 +/- 29.4 mL/min/1.73 m(2).  The incidence of pre-weaning AR was 11.5 %; the incidence of delayed graft function was 7.7 %.  Eighteen (69 %) of the children were tapered to spaced tacrolimus monotherapy, 10.5 +/- 2.2 months after transplantation.  The incidence of CMV, post-transplant lympho-proliferative disorder, and BK virus was 0 %; the incidence of post-transplant diabetes was 7.7 %.  The authors stated that although more follow-up is clearly needed, antibody pre-conditioning with alemtuzumab and tacrolimus monotherapy may be a safe and effective regimen in pediatric renal transplantation.

In a long-term, prospective randomized study, Ciancio and colleagues (2008) examined thymoglobulin versus alemtuzumab (with lower dose maintenance immunosuppression) versus daclizumab in renal transplantation at 24 months of follow-up.  A total of 90 deceased donor (DD) first renal transplant recipients were randomized into 3 different antibody induction groups: group A, thymoglobulin (Thymo); group B, alemtuzumab; and group C, daclizumab (Dac).  In groups A and C, the target trough levels of tacrolimus were 8 to 10 ng/mL, 1 g of MMF was administered twice-daily with maintenance methylprednisolone.  In group B, target tacrolimus trough levels were 4 to 7 ng/mL, 500 mg MMF administered twice-daily, without methylprednisolone.  African-Americans and Hispanics comprised more than 50 % in each group.  A minimum follow-up of 27 months showed no overall group differences in patient or graft survival (p = 0.89 and 0.66), but a trend towards worse death-censored graft survival in group B (p = 0.05).  Acute rejection rates were not significantly different: 6 (20 %), 7 (23 %), and 7 (23 %) in groups A, B, and C, respectively.  The incidence of chronic allograft nephropathy was higher in group B than in groups A and C (p = 0.008).  The mean calculated creatinine clearance at 24 months was 81.1 +/- 5.5, 64.4 +/- 4.5, and 80.7 +/- 5.7 in groups A, B, and C, respectively (p = 0.01 for B versus average of A and C).  The authors concluded that in this randomized 27-month minimum follow-up trial of predominantly non-Caucasian DD renal transplant recipients with alemtuzumab induction, lower maintenance tacrolimus, MMF, and steroid avoidance appeared less effective than either Thymo or Dac with higher maintenance immunosuppression.

Gomez-Almaguer and co-workers (2008) evaluated the safety and effectiveness of alemtuzumab in treating steroid-refractory acute GVHD (aGVHD), greater than or equal to grade II following hematopoietic stem cell transplantation (HSCT).  A total of 18 patients received subcutaneous alemtuzumab 10 mg daily on 5 consecutive days.  Response was assessed at day 28 following initiation of alemtuzumab.  Eight patients had grade II aGVHD, 8 had grade III, and 2 had grade IV.  The main organ involved was the liver in 4 patients, gastrointestinal (GI) tract in 5, skin in 3, skin and liver in 3, and skin and GI tract in 3.  Fifteen patients (83 %) responded to alemtuzumab, including 6 (33 %) with CR.  All 3 unresponsive patients died of GVHD.  Ten of 15 responders are alive at median follow-up of 11 months (range of 3 to 24 months).  Infections occurred in 14 patients, including CMV re-activation in 11.  Grade 3 neutropenia and thrombocytopenia occurred in 6 and 4 patients, respectively.  The authors concluded that alemtuzumab was well-tolerated, and induced promising response rates in steroid-refractory aGVHD.

In a prospective randomized study, Margreiter and associates (2008) examined the use of alemtuzumab and tacrolimus monotherapy following deceased donor renal transplantation.  A total of 65 patients in the study group received induction with alemtuzumab followed by delayed tacrolimus monotherapy, while the 66 patients in the control group were started on tacrolimus in combination with MMF and steroids.  Tacrolimus levels of 8 to 12 ng/ml for the first 6 months and 5 to 8 ng/ml thereafter were aimed for in both groups.  At 12 months the biopsy-proven rejection rate was 20 % in the study group and 32 % in the control group (p = 0.09).  Patient survival at 1 year was 98 % for both groups.  Graft survival was 96 % for the study group versus 90 % for the control group (p = 0.18).  Graft function was identical in both groups.  Adverse events were similar in both groups apart for more CMV infections in the study group.  At the end of the first year 82 % of the patients in the study group were steroid-free and 71 % continued on tacrolimus monotherapy.  These results suggested that alemtuzumab induction together with tacrolimus monotherapy is at least as efficient in renal transplantation as is a tacrolimus-based triple-drug regimen with a similar safety profile but more CMV infections.

Schadde et al (2008) compared outcomes of induction therapy with alemtuzumab with interleukin-2 (IL-2) receptor antagonists (RA) and anti-lymphocyte antibodies.  These researchers employed a retrospective sequential study design to examine 170 recipients of kidneys from donor after cardiac death (DCD) for survival, graft survival, time to first rejection, glomerular filtration and complications.  Patients were stratified into high-risk and low-risk groups based on the following criteria: panel of reactive antibodies greater than 20 %, re-transplantation, Afro-American race.  Induction with alemtuzumab was compared with ATG in the high-risk and with IL-2RA in the low-risk group.  Patients received triple immunosuppression with steroids, MMF and calcineurin inhibitors.  Patient survival, graft survival, rejection rate and glomerular filtration rate did not significantly differ between patients treated with alemtuzumab versus IL-2RAs or ATG.  There was a trend towards reduced graft survival and patient survival in the alemtuzumab group.  There was an increased incidence of CMV infections in the alemtuzumab-induced group and a trend towards increased BK virus and bacterial infections.  Induction of DCD kidney transplants with alemtuzumab compared to IL-2RA and ATG has no significant impact on AR.  It appears however that CMV infections are increased in patients induced with alemtuzumab.  The authors concluded that induction with alemtuzumab does not confer any advantage over traditional induction agents.

In a meta-analysis, Shou et al (2009) examined the safety and effectiveness of induction therapy with alemtuzumab in kidney transplantation (KTx).  Relevant papers were searched, essentially in the PubMed database and the Cochrane library.  After a thorough review, randomized controlled trials (RCTs) comparing the outcome of KTx using alemtuzumab induction therapy (test group) with a control group were collected according to the inclusion criteria.  Data of general characteristic of studies and major outcomes of KTx were extracted and meta-analyses were performed with RevMan 4.2 software.  The odds ratio (OR) with a 95 % confidence intervals (CI) was the principle measurement of effect.  A total of 5 RCTs were included.  The Chi-square test showed no significant between-study heterogeneity, thus fixed effect model was employed.  Sub-group analysis with studies including alemtuzumab induction followed by a tacrolimus-based immunosuppressive regimen showed that the acute rejection rate (ARR) was lower relative to the control (OR = 0.59, 95 % CI: 0.34 to 1.01, p = 0.05).  However, meta-analysis with all included studies revealed that neither ARR nor patient/graft survival rates differ significantly between the test and the control group, but the CMV infection rate was higher in the test group (OR 2.50, 95 % CI: 1.22 to 5.12, p = 0.01).  A great number of the test group recipients safely remained on a regimen that was steroid-free and with a reduced dose of conventional immunosuppressive drugs.  The authors concluded that alemtuzumab induction therapy for KTx was an effective and safe protocol in the tested follow-up period.  Steroid avoidance and a dose reduction of conventional immunosuppressive drugs after alemtuzumab induction therapy may have clinical importance.  However, they stated that high quality RCTs with larger population and longer follow-up are needed for a more accurate and objective appraisal of this novel protocol.

Rabie and Nevo (2009) noted that immune-mediated polyradiculoneuropathies are usually categorized into (i) Guillain-Barré syndrome (GBS), and (ii) chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).  In children, sub-acute inflammatory demyelinating polyradiculoneuropathy is included in CIDP.  Immune polyradiculoneuropathies are not exclusively demyelinating, and axonal forms also responding favorably to immunotherapy occur.  Evidence-based data on efficacy of therapy in children is lacking, relying on retrospective data, open label studies on small numbers of children, and mainly adult derived data.  Immunotherapy (intravenous human immunoglobulin [IVIG] and plasmapheresis) shortens GBS recovery time with most children recovering completely.  Childhood CIDP usually responds to steroids and slow tapering is required to prevent relapses.  Plasmapheresis and IVIG are also effective.  Children with CIDP who are resistant to steroids, IVIG, and steroid-dependent patients present a therapeutic challenge.  Immunosuppressive agents including methotrexate, azathioprine and cyclosporine are helpful in some cases.  Anecdotal reports of treatment with interferons alpha or beta and monoclonal antibodies against specific B-cell antigens (e.g., rituximab, alemtuzumab) have been described in limited case reports.  Furthermore, in a review on current treatments of CIDP (Brannagan, 2009), alemtuzumab is not listed as one of the therapeutic options.

Dalakas et al (2009) examine if one series of alemtuzumab infusions in patients with sporadic inclusion-body myositis (sIBM) depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease.  A total of 13 sIBM patients with established 12-month natural history data received 0.3 mg/kg/day alemtuzumab for 4 days.  The study was powered to capture greater than or equal to 10 % increase strength 6 months after treatment.  The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements.  Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies.  Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies.  During a 12-month observation period, the patients' total strength had declined by a mean of 14.9 % based on Quantitative Muscle Strength Testing.  Six months after therapy, the overall decline was only 1.9 % (p < 0.002), corresponding to a 13 % differential gain.  Among those patients, 4 improved by a mean of 10 % and 6 reported improved performance of daily activities.  The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8 % during the observation period but an improvement by 11.4 % (p < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier.  Depletion of peripheral blood lymphocytes, including the naive and memory CD8+ cells, was noted 2 weeks after treatment and persisted up to 6 months.  The effector CD45RA(+)CD62L(-) cells, however, started to increase 2 months after therapy and peaked by the 4th month.  Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50 % (p < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and alphaB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased.  This proof-of-principle study provided insights into the pathogenesis of inclusion-body myositis and concluded that in sIBM one series of alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. The authors stated that these encouraging results, the first in sIBM, warrant a future study with repeated infusions.

In a phase II clinical study, Angiolillo et al (2009) examined the effects of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia (ALL).  A total of 13 eligible patients were enrolled in this trial.  Campath-1H was initially administered as an intravenous infusion over 2 hrs, 5 times per week for 1 week, then 3 times per week for 3 additional weeks.  Patients with SD or better on day 29 could continue on to combination therapy with Campath-1H, methotrexate, and 6-mercaptopurine for 2 additional cycles.  One of 13 patients enrolled had a CR to Campath-1H and 4 had SD.  Dose limiting toxicity occurred in 2 out of 9 fully evaluable patients (grade IV pain and grade III allergic reaction/hypersensitivity).  No patients received combination therapy.  Serum Campath-1H concentrations appeared to be somewhat lower in children with ALL compared with adult patients with CLL.  The authors concluded that although a single CR was observed, activity of single agent Campath-1H appears limited.  They stated that these findings do not support future single agent evaluation of Campath-1H in children with relapsed ALL.

Gotlib (2010) assessed recent developments in the classification and treatment of eosinophilic myeloid disorders in the context of reactive, lymphocyte-variant, and idiopathic eosinophilias.  The revised 2008 World Health Organization (WHO) classification recognizes both molecularly defined (myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1) and undefined (chronic eosinophilic leukemia, not otherwise specified) eosinophilic myeloid disorders.  An increasingly sophisticated understanding of the molecular underpinnings of eosinophilia has translated into rational use of biologically targeted therapies such as imatinib mesylate.  Conventional cytotoxics and interferon-alpha still have an established role in treating these diseases.  Although studied in idiopathic hyper-eosinophilic syndrome, the therapeutic niche of mepolizumab and alemtuzumab antibody therapy in eosinophilic myeloid diseases has yet to be established.

Gotlib (2011) stated that the eosinophilias entail a broad range of non-hematological (secondary or reactive) and hematological (primary, clonal) disorders with potential for end-organ damage.  Hyper-eosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1,500/mm(3) and may be associated with tissue damage.  After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder.  Disease prognosis relies on identifying the subtype of eosinophilia.  After evaluation of secondary causes of eosinophilia, the 2008 WHO establishes a semi-molecular classification scheme of disease subtypes including myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1, chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), lymphocyte-variant hypereosinophilia, and idiopathic hyper-eosinophilic syndrome (HES), which is a diagnosis of exclusion.  The goal of therapy is to mitigate eosinophil-mediated organ damage.  For patients with milder forms of eosinophilia (e.g. less than 1,500/mm(3)) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken.  Identification of re-arranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib.  Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES.  Hydroxyurea and interferon-alpha have demonstrated efficacy as initial treatment and steroid-refractory cases of HES.  In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients.  Furthermore, the author noted that although clinical trials have been performed with anti IL-5 (mepolizumab) and anti-CD52 (alemtuzumab) antibodies, their therapeutic niche in primary eosinophilic diseases and HES have yet to be established.

Ong and Denton (2010) reviewed the evidence and recent developments leading to novel therapeutics in scleroderma.  Recent advances have been made in understanding the key pathogenetic aspects of scleroderma, and these have led to potential targeted therapeutic agents for the management of these patients.  Preliminary data from early clinical trials suggest that tyrosine kinase molecules may be potential candidates for therapy, especially in the fibrotic phase of the disease.  On the basis of the new insights into the key role of effector T cells, in particular Th-17 and T regulatory subsets, T-cell-directed therapies including halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinically beneficial.  By analogy, recent clinical studies with rituximab in diffuse cutaneous systemic sclerosis lend support that B cells may be important in the pathogenesis of the disease.  Endothelin receptor antagonists, 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, and phosphodiesterase type V inhibitor have been shown to be useful to treat the vascular manifestations associated with systemic sclerosis.  Hematopoietic stem cell transplantation following immune ablation holds considerable promise in re-setting of the immune system, and trial results are awaited.  The authors concluded that although there is still no treatment that is unequivocally effective for scleroderma, there have been some promising developments over the past number of years with identification of novel candidate targets and innovative strategies, including targeted immunomodulatory therapies, tyrosine kinase inhibitors and agents that may promote vascular repair.  They stated that these recent findings will need to be confirmed by larger, multi-center, RCTs.

In a pilot study, Risitano et al (2010) examined the effectiveness of alemtuzumab-based experimental immunosuppressive treatment (IST) regimen in 35 patients with severe aplastic anemia (AA), pure red cell (PRCA) or pure white cell aplasia (PWCA).  Alemtuzumab total dose was 73 to 103 mg (subcutaneous), followed by cyclosporine.  No serious toxicity due to the regimen was observed.  Adverse events were clinically irrelevant; infectious events were rare.  The total response rate was 58 %, 84 % and 100 % in severe AA, PRCA and PWCA, respectively, with corresponding 6-month cumulative response probabilities of 84 %, 84 % and 100 %.  The authors concluded that subcutaneous alemtuzumab is a feasible and sufficiently safe IST regimen for patients suffering from immune-mediated marrow failures.  The findings of this pilot study were confounded by the concomitant use of alemtuzumab and cyclosporine.  The authors also noted that these findings paved the way of systematic investigation in comparisons to standard immunosuppressive regimens.

Gomez-Almaguer et al (2010) treated 14 AA patients with alemtuzumab (median age of 23 years).  Ten milligrams of alemtuzumab were injected subcutaneously each day for 5 consecutive days.  Cyclosporine A was also administered orally at a dose of 2 mg/kg every 12 hrs for 3 months, and then gradually tapered.  Response to alemtuzumab was followed for a median of 20 months.  There were 8 responses (57.1 %), 2 complete and 6 partial.  Whereas 6 (42.8 %) patients were non-responders.  Median complete blood count values on alemtuzumab responders were Hb 13.1 mg/dL, absolute neutrophil count 2.4 x 10(9)/L, and platelets 97.5 x 10(9)/L.  The authors concluded that a good response was produced in 57 % of AA patients with the administration of alemtuzumab, who lacked a stem cell donor.  Again, the findings of this study were confounded by the concomitant use of alemtuzumab and cyclosporine.  The authors also noted that more studies are needed regarding the use of alemtuzumab in AA.

Guidelines from the National Comprehensive Cancer Network (2012) recommend the use of alemtuzumab for as a single-agent therapy for mycosis fungoides/Sezary syndrome with histologic evidence of large cell transformation and aggressive growth rate in noncandidates for transplant with either: 1) stage IA-IIA MF with histologic evidence of folliculotropic or large cell transformation or stage IIB with generalized extent tumor, transformed, and/or folliculotropic disease in combination with skin-directed therapy; or 2) stage IV non-Sezary or visceral disease.

Shukla et al (2012) noted that histiocytic sarcoma (HS) is an exceedingly rare tumor and carries a dismal prognosis when patients present with advanced-stage disease.  Because of the poor response rates to conventional chemotherapy and the rarity of the disease, no standard of care exists for patients with HS.  The authors reported the single-agent use of alemtuzumab in 2 patients who had advanced-stage HS.  Two patients with chemotherapy-refractory, metastatic HS with tumors that expressed the CD52 antigen received a prolonged course of treatment with the anti-CD52 monoclonal antibody alemtuzumab.  Resected tumor samples from both patients demonstrated CD52 expression.  Both patients had marked responses to alemtuzumab.  One patient had a CR with no evidence of disease for greater than 5 years.  The second patient had a major response to alemtuzumab and also remained alive with no evidence of disease for greater than 4 years.  The authors concluded that further studies need to be performed to examine CD52 expression and function in HS, as well as the role of alemtuzumab in a larger cohort of patients since the clinical impact of alemtuzumab in the 2 patients described in this report was very encouraging. 

Tzachanis et al (2014) reported on the case of a 79-year old man with chronic lymphocytic leukemia who presented with GBS with features overlapping with the Miller Fisher syndrome and Bickerstaff brainstem encephalitis and positive anti-ganglioside GQ1b antibody about 6 months after treatment with bendamustine and rituximab.  His clinical and neurologic condition continued to deteriorate despite sequential treatment with corticosteroids, IVIG and plasmapheresis, but in the end, he had a complete and durable response to treatment with alemtuzumab.  The findings of this single-case study needs to be validated by well-designed studies

Menge and colleagues (2014) stated that alemtuzumab is a humanized monoclonal antibody that rapidly depletes CD52+ cells of the lymphoid lineage from peripheral blood, but spares lymphoid precursor cells.  Clinical efficacy and safety data from clinical phase II and III trials -- all using interferon-β-1a as active comparator --were summarized and placed in perspective.  These researchers further analyzed the differential reconstitution of T and B cells as a potential mode of action and the pathogenic link to treatment-emergent secondary autoimmune conditions.  Given recent positive opinions by regulatory agencies, this new drug will be positioned for the treatment of active relapsing-remitting MS and enlarge our therapeutic armamentarium.  Moreover, they noted that Genzyme has announced that it is preparing to re-submit an application to the FDA for approval in the U.S. addressing the agency’s concerns.

Chow and Chan (2013) reported on the cases of 3 patients with pure red cell aplasia (with or without co-existing large granular lymphocytic leukemia, who remained transfusion-dependent despite treatment with established first-line therapy) who were treated with low-dose subcutaneous alemtuzumab 15 mg twice to thrice per week, for 3 to 4 weeks.  The mean response time was 17 days compared with a response time of at least 61 days on standard first-line therapy.  There were no serious side-effects and the mean duration of remission was 13 months.  The authors concluded that low-dose subcutaneous alemtuzumab is a safe and effective treatment for pure red cell aplasia and further trials should be conducted to compare the long-term effectiveness of this treatment with conventional therapy.

Dvorak and colleagues (2014) stated that for infants with severe combined immunodeficiency (SCID) the ideal conditioning regimen before allogeneic hematopoietic cell transplantation would omit cytotoxic chemotherapy to minimize short- and long-term complications.  These researchers performed a prospective pilot trial with alemtuzumab monotherapy to overcome natural killer-cell mediated immunologic barriers to engraftment.  They enrolled 4 patients who received CD34-selected haploidentical cells, 2 of whom failed to engraft donor T cells.  The 2 patients who engrafted had delayed T-cell reconstitution, despite rapid clearance of circulating alemtuzumab.  The authors concluded that although well-tolerated, alemtuzumab failed to overcome immunologic barriers to donor engraftment.  Furthermore, alemtuzumab may slow T-cell development in patients with SCID in the setting of a T-cell depleted graft.

Furthermore, the NCCN’s Drugs & Biologics Compendium (2014) does not list pure red cell aplasia and severe combined immunodeficiency as recommended indications of alemtuzumab.

Alemtuzumab is usually administered as an intravenous infusion over a 2-hr period.  The most common side effects associated with its use are infusion reactions (e.g., chills, dyspnea, hypotension, nausea, pyrexia, rash, tachycardia, and urticaria), cytopenias (e.g., anemia, lymphopenia, neutropenia, and thrombocytopenia), immunosuppression/infections (e.g., CMV infection, CMV viremia, and other infections), GI symptoms (e.g., emesis, nausea, and abdominal pain), and neurological symptoms (e.g., anxiety and insomnia).


Note on US Campath Distribution Program:

Genzyme has developed the Campath Distribution Program to ensure continued access to Campath (alemtuzumab) for appropriate patients. Effective September 4, 2012 Campath will no longer be available commercially, but will be provided through the Campath Distribution Program free of charge. In order to receive Campath, the healthcare provider is required to document and comply with certain requirements. Please contact the numbers below to learn more.

Campath Distribution Program: 1-877-422-6728

Genzyme Medical Information: 1-800-745-4447 Option #2


CPT Codes / HCPCS Codes / ICD-9 Codes
Other CPT codes related to the CPB:
38204 - 38242 Bone marrow or stem cell services/procedures
96365 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
96366     each additional hour (List separately in addition to code for primary procedure)
96369 Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); initial, up to 1 hour, including pump set-up and establishment of subcutaneous infusion site(s)
96370     each additional hour (List separately in addition to code for primary procedure)
96413 Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug
96415     each additional hour (List separately in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
J9010 Alemtuzumab, 10 mg
Other HCPCS codes related to the CPB:
J7506 Prednisone, oral, per 5mg
J8530 Cyclophosphamide, oral, 25 mg
J9000 Doxorubicin HCl, 10 mg
J9070 Cyclophosphamide, 100 mg
J9185 Fludarabine phosphate, 50 mg
J9370 Vincristine sulfate, 1 mg
Q0083 - Q0085 Chemotherapy administration
Q2050 Injection, doxorubicin hydrochloride, liposomal, not otherwise specified, 10 mg
S0172 Chlorambucil, oral, 2 mg
S2150 Bone marrow or blood-derived stem-cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre-and post-transplant care in the global definition
ICD-9 codes covered if selection criteria are met:
200.10 - 200.18 Lymphosarcoma
200.60 - 200.68 Anaplastic large cell lymphoma
200.80 - 200.88 Other named variants of lymphosarcoma and reticulosarcoma and other specified malignant tumors of lymphatic tissue
202.10 - 202.18 Mycosis fungoides
202.20 - 202.28 Sezary's disease
202.70 - 202.78 Peripheral T-cell lymphoma
202.80 - 202.88 Other lymphomas
204.10 - 204.11 Chronic lymphoid leukemia
204.80 - 204.88 Other lymphoid leukemia [T-cell prolymphocytic leukemia]
273.3 Macroglobulinemia
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
171.0 - 171.9 Malignant neoplasm of connective and other soft tissue
204.00 - 204.02 Acute lymphoid leukemia
238.72 Low grade myelodysplastic syndrome lesions
238.73 High grade myelodysplastic syndrome lesions
238.74 Myelodysplastic syndrome with 5q deletion
238.75 Myelodysplastic syndrome, unspecified
273.2 Other paraproteinemias
279.2 Combined immunity deficiency [severe]
279.50 - 279.53 Graft-versus host disease
284.0 - 284.9 Aplastic anemia
287.0 Allergic purpura
289.9 Unspecified diseases of blood and blood-forming organs [cytopenia]
340 Multiple sclerosis
357.0 - 357.9 Inflammatory and toxic neuropathy
362.18 Retinal vasculitis
446.29 Other specified hypersensitivity angiitis
447.6 Arteritis, unspecified
447.8 Other specified disorders of arteries and arterioles
710.1 Systemic sclerosis
711.00 - 711.99 Arthropathy associated with infections
712.10 - 712.99 Crystal arthropathies
713.0 - 713.8 Arthropathy associated with other disorders classified elsewhere
714.0 - 714.9 Rheumatoid arthritis and other inflammatory polyarthropathies
715.00 - 715.99 Osteoarthrosis and allied disorders
716.00 - 716.99 Other and unspecified arthropathies
719.00 - 719.99 Other and unspecified disorders of joint
720.0 - 720.9 Ankylosing spondylitis and other inflammatory spondylopathies
721.0 - 721.91 Spondylosis and allied disorders
728.0 - 728.9 Disorders of muscle, ligament, and fascia
729.1 Myalgia and myositis, unspecified
996.81 - 996.84, 996.86 - 996.87 Complications of transplanted organ
996.85 Complications of bone marrow transplant [graft-versus-host disease]
V42.0 - V42.2, V42.6 - V42.7, V42.83 - V42.84 Organ or tissue replaced by transplant
Other ICD-9 codes related to the CPB:
V58.11 Encounter for antineoplastic chemotherapy

The above policy is based on the following references:
  1. Kennedy GA, Seymour JF, Wolf M, et al. Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol. 2003;71(4):250-256.
  2. Lundin J, Hagberg H, Repp R, et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood. 2003;101(11):4267-4272.
  3. Capalbo S, Delia M, Dargenio M, et al. Mycosis fungoides/Sezary syndrome: A report of three cases treated with Campath-1H as salvage treatment. Med Oncol. 2003;20(4):389-396.
  4. Fajemisin B. Alemtuzumab for chronic lymphocytic leukaemias. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2003.
  5. Reiff A. A review of Campath in autoimmune disease: Biologic therapy in the gray zone between immunosuppression and immunoablation. Hematology. 2005;10(2):79-93.
  6. Hadj Tahar A. Alemtuzumab for B-cell chronic lymphocytic leukemia. Ottawa, ON: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); 2005.
  7. Fraser G, Smith CA, Imrie K, Meyer R; Hematology Disease Site Group. Alemtuzumab in chronic lymphocytic leukemia: A clinical practice guideline. Evidence-based Series No. 6-16. Toronto, ON: Cancer Care Ontario (CCO); June 14, 2006.
  8. Fiegl M, Falkner A, Hopfinger G, et al. Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: A nation-wide retrospective study in Austria. Cancer. 2006;107(10):2408-2416.
  9. Kirsch BM, Haidinger M, Zeyda M, et al. Alemtuzumab (Campath-1H) induction therapy and dendritic cells: Impact on peripheral dendritic cell repertoire in renal allograft recipients. Transpl Immunol. 2006;16(3-4):254-257.
  10. National Horizon Scanning Centre (NHSC). Alemtuzumab (MabCampath) for chronic lymphocytic leukaemia (first-line): Horizon scanning technology ultra-orphan note. Birmingham, UK: NHSC; 2006.
  11. National Cancer Institute (NCI). FDA approval for alemtuzumab. Brand Name(s): Campath. Drug Information. Bethesda, MD: NCI; September 20, 2007. Available at: Accessed June 9, 2008.
  12. Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007;25(35):5616-5623.
  13. Huang E, Cho YW, Hayashi R, Bunnapradist S. Alemtuzumab induction in deceased donor kidney transplantation. Transplantation. 2007;84(7):821-828.
  14. Reams BD, Musselwhite LW, Zaas DW, et al. Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation. Am J Transplant. 2007;7(12):2802-2808.
  15. Shapiro R, Ellis D, Tan HP, et al. Alemtuzumab pre-conditioning with tacrolimus monotherapy in pediatric renal transplantation. Am J Transplant. 2007;7(12):2736-2738.
  16. Muraro PA, Bielekova B. Emerging therapies for multiple sclerosis. Neurotherapeutics. 2007;4(4):676-692.
  17. Waubant E. Emerging therapies for MS. Rev Neurol (Paris). 2007;163(6-7):688-696.
  18. Demko S, Summers J, Keegan P, Pazdur R. FDA drug approval summary: Alemtuzumab as single-agent treatment for B-cell chronic lymphocytic leukemia. Oncologist. 2008;13(2):167-174.
  19. Lee RW, D'Cruz DP. Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis. Drugs. 2008;68(6):747-770.
  20. Ciancio G, Burke GW 3rd. Alemtuzumab (Campath-1H) in kidney transplantation. Am J Transplant. 2008;8(1):15-20.
  21. Ciancio G, Burke GW, Gaynor JJ, et al. A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow-up. Clin Transplant. 2008;22(2):200-210.
  22. Gómez-Almaguer D, Ruiz-Argüelles GJ, del Carmen Tarín-Arzaga L, et al. Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2008;14(1):10-15.
  23. Margreiter R, Klempnauer J, Neuhaus P, et al. Alemtuzumab (Campath-1H) and tacrolimus monotherapy after renal transplantation: Results of a prospective randomized trial. Am J Transplant. 2008;8(7):1480-1485.
  24. Schadde E, D'Alessandro AM, Knechtle SJ, et al. Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death. Transpl Int. 2008;21(7):625-636.
  25. Warnke C, Kieseier BC, Zettl U, Hartung HP. Possibilities and risks of the monoclonal antibody alemtuzumab as a new treatment option for multiple sclerosis. Nervenarzt. 2009;80(4):468-474.
  26. Dhesi S, Boland B, Colquhoun S. Alemtuzumab and liver transplantation: A review. Curr Opin Organ Transplant. 2009;14(3):245-249.
  27. Rabie M, Nevo Y. Childhood acute and chronic immune-mediated polyradiculoneuropathies. Eur J Paediatr Neurol. 2009;13(3):209-218.
  28. Brannagan TH 3rd. Current treatments of chronic immune-mediated demyelinating polyneuropathies. Muscle Nerve. 2009;39(5):563-578.
  29. Shou ZF, Zhou Q, Cai JR, et al. Efficacy and safety of induction therapy with alemtuzumab in kidney transplantation: A meta-analysis. Chin Med J (Engl). 2009;122(14):1692-1698.
  30. Martínez C, Solano C, Ferrá C, et al; Spanish Group for Stem Cell Transplantation (Grupo Español de Trasplante Hemopoyético y Terapia Celular). Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: Results of a phase II study. Biol Blood Marrow Transplant. 2009;15(5):639-642.
  31. Dalakas MC, Rakocevic G, Schmidt J, et al. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain. 2009;132(Pt 6):1536-1544.
  32. Trebst C, Voss E, Skripuletz T, Stangel M. Specific immune intervention with monoclonal antibodies for the treatment of multiple sclerosis. Curr Med Chem. 2010;17(7):640-650.
  33. Gotlib J. Eosinophilic myeloid disorders: New classification and novel therapeutic strategies. Curr Opin Hematol. 2010;17(2):117-124.
  34. Ong VH, Denton CP. Innovative therapies for systemic sclerosis. Curr Opin Rheumatol. 2010;22(3):264-272.
  35. Risitano AM, Selleri C, Serio B, et al; Working Party Severe Aplastic Anaemia (WPSAA) of the European Group for Blood and Marrow Transplantation (EBMT). Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single-lineage marrow failure: A pilot study and a survey from the EBMT WPSAA. Br J Haematol. 2010;148(5):791-796.
  36. Gómez-Almaguer D, Jaime-Pérez JC, Garza-Rodríguez V, et al. Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia. Ann Hematol. 2010;89(3):299-303.
  37. Minagar A, Alexander JS, Sahraian MA, Zivadinov R. Alemtuzumab and multiple sclerosis: Therapeutic application. Expert Opin Biol Ther. 2010;10(3):421-429.
  38. Wolff D, Schleuning M, von Harsdorf S, et al. Consensus conference on clinical practice in chronic GVHD: Second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2011;17(1):1-17.
  39. Gotlib J. World Health Organization-defined eosinophilic disorders: 2011 update on diagnosis, risk stratification, and management. Am J Hematol. 2011;86(8):677-688.
  40. Skoetz N, Bauer K, Elter T, et al. Alemtuzumab for patients with chronic lymphocytic leukaemia. Cochrane Database Syst Rev. 2012;(2):CD008078.
  41. National Comprehensive Cancer Network (NCCN). Non-Hodgkin's lymphomas. NCCN Clinical Practice Guidelines in Oncology v.3.2012. Fort Washington, PA: NCCN; 2012.
  42. Shukla N, Kobos R, Renaud T, et al. Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab. Cancer. 2012;118(15):3719-3724.
  43. Brown JW, Coles AJ. Alemtuzumab: Evidence for its potential in relapsing-remitting multiple sclerosis. Drug Des Devel Ther. 2013;7:131-138.
  44. Silva-Fernandez L, Loza E, Martinez-Taboada VM, et al; from the Systemic Autoimmune Diseases Study Group of the Spanish Society for Rheumatology (EAS-SER). Biological therapy for systemic vasculitis: A systematic review. Semin Arthritis Rheum. 2014;43(4):542-557.
  45. Nikiforow S, Kim HT, Bindra B, et al. Phase I study of alemtuzumab for therapy of steroid-refractory chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2013;19(5):804-811.
  46. Penninga L, Møller CH, Penninga EI, et al. Antibody induction therapy for lung transplant recipients. Cochrane Database Syst Rev. 2013;11:CD008927.
  47. Dearden C, Johnson R, Pettengell R, Devereux S, Cwynarski K, Whittaker S, McMillan A. Guidelines for the management of mature T-cell and NK-cell neoplasms (excluding cutaneous T-cell lymphoma). London, UK: British Committee for Standards in Haematology (BCSH); August 2013.
  48. Chow JK, Chan TK. Low-dose subcutaneous alemtuzumab is a safe and effective treatment for chronic acquired pure red cell aplasia. Hong Kong Med J. 2013;19(6):549-552.
  49. Penninga L, Wettergren A, Wilson CH, et al.  Antibody induction versus placebo, no induction, or another type of antibody induction for liver transplant recipients. Cochrane Database Syst Rev. 2014;6:CD010253.
  50. Wingerchuk DM, Carter JL. Multiple sclerosis: Current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014;89(2):225-240.
  51. Tzachanis D, Hamdan A, Uhlmann EJ, Joyce RM. Successful treatment of refractory Guillain-Barrre syndrome with alemtuzumab in a patient with chronic lymphocytic leukemia. Acta Haematol. 2014;132(2):240-243
  52. National Comprehensive Cancer Network (NCCN). Alemtuzumab. NCCN Drugs & Biologics Compendium. Fort Washington, PA: NCCN; 2014.
  53. Menge T, Stüve O, Kieseier BC, Hartung HP. Alemtuzumab: The advantages and challenges of a novel therapy in MS. Neurology. 2014;83(1):87-97.
  54. Dvorak CC, Horn BN, Puck JM, et al. A trial of alemtuzumab adjunctive therapy in allogeneic hematopoietic cell transplantation with minimal conditioning for severe combined immunodeficiency. Pediatr Transplant. 2014;18(6):609-616.
  55. The 3C Study Collaborative Group. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): A randomised trial. Lancet. 2014 Jul 26 [Epub ahead of print].

email this page   

Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
Back to top