Elotuzumab (Empliciti)

Number: 0899

Policy

Note: Requires Precertification.

Precertification of elotuzumab is required of all Aetna participating providers and members in applicable plan designs. For precertification, call (866) 752-7021 (Commercial), (866) 503-0857 (Medicare), or fax (866) 267-3277.

Aetna considers elotuzumab (Empliciti) medically necessary for the treatment of multiple myeloma when all of the following criteria are met: 

  • The disease is relapsed or progressive; and
  • Elotuzumab (Empliciti) will be used in any of the following regimens:

    • In combination with lenalidomide and dexamethasone in persons who have received 1 to 3 prior therapies; or
    • In combination with bortezomib and dexamethasone in members who have received at least one prior therapy; or
    • In combination with pomalidomide and dexamethasone in persons who have received at least two prior therapies, including an immunomodulatory agent and a proteasome inhibitor.

Aetna considers continued treatment with elotuzumab medically necessary in members requesting reauthorization for a medically necessary indication when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

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

  • B-cell lymphoma (including lymphoplasmacytic lymphoma)
  • Newly diagnosed (not previously treated) multiple myeloma
  • Non-Hodgkin lymphoma (including diffuse large B-cell lymphoma, follicular lymphoma, indolent B-cell lymphoma, mantle-cell lymphoma, and primary mediastinal lymphoma)
  • Primary amyloidosis
  • Smoldering multiple myeloma.

Dosing Recommendations

Elotuzumab is available as Empliciti in 300 mg and 400 mg vials. Recommended dosing is:

Elotuzumab with lenalidomide and dexamethasone: 10 mg/kg administered intravenously every week for the first 2 cycles and every 2 weeks thereafter until disease progression or unacceptable toxicity.  Pre-medicate with dexamethasone, diphenhydramine, ranitidine and acetaminophen.

Elotuzumab with pomalidomide and dexamethasone: 10 mg/kg administered intravenously every week for the first two cycles and 20 mg/kg every 4 weeks thereafter until disease progression or unacceptable toxicity.  Pre-medicate with dexamethasone, diphenhydramine, ranitidine and acetaminophen.

Source: Bristol-Myers Squibb Company, 2019


Background

U.S. Food and Drug Administration (FDA)-Approved Indications

  • Empliciti is indicated in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.
  • Empliciti is indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

Compendial Uses

  • Therapy for previously treated multiple myeloma for relapsed or progressive disease in combination with bortezomib and dexamethasone

Multiple myeloma (MM) is characterized by the neoplastic proliferation of clonal plasma cells in the bone marrow resulting in skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures. Additional disease-related complications include hypercalcemia, renal insufficiency, anemia, and infections.

Schmidt-Wolf and colleagues (2014) stated that MM, with an incidence of 4 to 6/100,000 inhabitants, is a fairly frequent malignancy of B cells.  The incidence increases markedly with age. While standard treatments are associated with high response rates in patients with newly diagnosed multiple myeloma (MM), effective therapy for relapsed and refractory patients remains a challenge. The present standard of care in the progressive or refractory MM was elaborated by the working group "Refractory Multiple Myeloma" using an extensive literature search for studies published between 2003 and 2013.  Outside of clinical trials, high-dose therapy with stem cell transplantation is recommended in fit patients up to 75 years without significant co-morbidities.  Ongoing studies address the question about the least toxic and the most effective treatment.  Therefore, inclusion of patients in therapeutic trials and use of novel agent combinations is highly recommended including the use of 3rd generation immunomodulatory drugs (IMIDs; e.g., pomalidomide), new proteasome inhibitors (e.g., carfilzomib, ixazomib or oprozomib), antibodies (e.g., daratumumab, denosumab, elotuzumab, romosozumab, siltuximab, tabalumab), Bruton's tyrosine kinase (BTK)-, heat shock protein (HSP)-inhibitors and other innovative phase I/II agents.

Ashjian and Redic (2016) noted that there have been a number of recent advances in the treatment of patients with relapsed and refractory MM.  However, despite additional Food and Drug Administration (FDA)-approved therapies including carfilzomib and pomalidomide as well as clinical trials investigating new combinations of existing treatments, MM remains an incurable disease.  New therapies currently in the drug development pipeline for relapsed and refractory MM include additional proteasome inhibitors (ixazomib, marizomib, oprozomib), histone deacetylase inhibitors (panobinostat, quisinostat, ricolinostat), mAbs (daratumumab, elotuzumab), BTK inhibitors (ibrutinib) and others.

On November 30, 2015, the FDA approved elotuzumab (Empliciti) in combination with lenalidomide and dexamethasone to treat people with MM who have received 1 to 3 prior medications.  The FDA approval was based on the findings of the phase III clinical trial by Lonial et al (2015).  The most common side effects of Empliciti are constipation, cough, diarrhea, fatigue, nasopharyngitis, pneumonia, pyrexia, decreased appetite, peripheral neuropathy, and upper respiratory tract infection.

Lonial and associates (2013) reviewed the scientific literature regarding the development and clinical investigation of a CS1-targeted monoclonal antibody (mAb), elotuzumab, for the potential treatment of MM.  Elotuzumab is an immunostimulatory mAb targeting signaling lymphocytic activation molecule F7 (SLAMF7). This binding triggers the interactions of natural killer T cells to mediate the destruction of myeloma cells via the antibody dependent cellular cytotoxicity process. The authors summarized the pre-clinical pharmacological data, along with safety, tolerability and effectiveness of elotuzumab alone and in combination. They stated that elotuzumab, in combination with lenalidomide, showed high overall response rate (ORR) in phase I and II clinical trials.  Furthermore, the improvements observed in progression-free survival (PFS) suggested superiority over lenalidomide/dexamethasone alone, with a similar tolerability profile.  These researchers noted that while elotuzumab is associated with a higher incidence of infusion reactions, these can be managed with appropriate pre-medication.  The authors noted that the high activity of the elotuzumab/lenalidomide combination is being further investigated in phase III clinical trials.  They stated that elotuzumab represents an exciting potential therapeutic option for patients with MM, including those with relapsed and refractory disease, as well as in the induction and post-transplant maintenance settings, and possibly even for early therapy in patients with high-risk smoldering myeloma.

In a phase III, multi-center, randomized controlled trial (RCT), Lonial and colleagues (2015) randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group).  Co-primary end-points were PFS and the ORR.  Final results for the co-primary end-points were reported on the basis of a planned interim analysis of PFS.  Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group.  After a median follow-up of 24.5 months, the rate of PFS at 1 year in the elotuzumab group was 68 %, as compared with 57 % in the control group; at 2 years, the rates were 41 % and 27 %, respectively.  Median PFS in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio [HR] for progression or death in the elotuzumab group, 0.70; 95 % confidence interval [CI]: 0.57 to 0.85; p < 0.001).  The ORR in the elotuzumab group was 79 %, versus 66 % in the control group (p < 0.001).  Common grade 3 or 4 adverse events in the 2 groups were fatigue, lymphocytopenia, neutropenia, and pneumonia.  Infusion reactions occurred in 33 patients (10 %) in the elotuzumab group and were grade 1 or 2 in 29 patients.  The authors concluded that patients with relapsed or refractory MM who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30 % in the risk of disease progression or death.

On November 06, 2018, the FDA approved elotuzumab (Empliciti) in combination pomalidomide and dexamethasone (EPd) for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. This approval was based on results from ELOQUENT-3, a randomized, open-label, Phase 2 trial where EPd demonstrated benefit in patients with relapsed or refractory multiple myeloma, doubling both median progression-free survival (PFS) and overall response rate (ORR) versus pomalidomide and dexamethasone (Pd) (NCT02654132; Dimopoulos et al 2018).

Dimopoulos et al (2018) stated the  immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma. The immunomodulatory agent pomalidomide plus dexamethasone has been shown to be effective in patients with multiple myeloma that is refractory to lenalidomide and a proteasome inhibitor. Patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor were randomly assigned to receive elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone alone (control group). The primary end point was investigator-assessed progression-free survival. A total of 117 patients were randomly assigned to the elotuzumab group (60 patients) or the control group (57 patients). After a minimum follow-up period of 9.1 months, the median progression-free survival was 10.3 months in the elotuzumab group and 4.7 months in the control group. The hazard ratio for disease progression or death in the elotuzumab group as compared with the control group was 0.54 (95% confidence interval [CI], 0.34 to 0.86; P=0.008). The overall response rate was 53% in the elotuzumab group as compared with 26% in the control group (odds ratio, 3.25; 95% CI, 1.49 to 7.11). The most common grade 3 or 4 adverse events were neutropenia (13% in the elotuzumab group vs. 27% in the control group), anemia (10% vs. 20%), and hyperglycemia (8% vs. 7%). A total of 65% of the patients in each group had infections. Infusion reactions occurred in 3 patients (5%) in the elotuzumab group. The authors concluded that among patients with multiple myeloma in whom treatment with lenalidomide and a proteasome inhibitor had failed, the risk of progression or death was significantly lower among those who received elotuzumab plus pomalidomide and dexamethasone than among those who received pomalidomide plus dexamethasone alone. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-3 ClinicalTrials.gov number, NCT02654132).

Dimopoulos and colleagues (2020) stated that prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM).  In the ELOQUENT-2 trial, elotuzumab plus lenalidomide / dexamethasone (ERd) significantly improved PFS versus lenalidomide / dexamethasone (Rd) in patients with RRMM and 1 to 3 prior lines of therapy (LoTs).  These investigators reported findings from the pre-planned final OS analysis after a minimum follow-up of 70.6 months, the longest reported for an antibody-based triplet in RRMM.  A total of 646 patients with RRMM and 1 to 3 prior LoTs were randomized 1:1 to ERd or Rd; PFS ORR were co-primary end-points.  OS was a key secondary end-point, with the final analysis planned after 427 deaths.  ERd demonstrated a statistically significant 8.7-month improvement in OS versus Rd (median of 48.3 versus 39.6 months; HR, 0.82 [95.4 % Cl: 0.68 to 1.00]; p = 0.0408 [less than allotted α of 0.046]), which was consistently observed across key pre-defined subgroups.  No additional safety signals with ERd at extended follow-up were reported.  The authors concluded that ERd was the 1st antibody-based triplet regimen shown to significantly prolong OS in patients with RRMM and 1 to 3 prior LoTs.  The magnitude of OS benefit was greatest among patients with adverse prognostic factors, including older age, International Staging System (ISS) stage III, International Myeloma Working Group (IMWG) high-risk disease, and 2 to 3 prior LoTs.

Hose and colleagues (2020) noted that elotuzumab (elo), plus lenalidomide (len) and dexamethasone (dex) was approved for relapsed/refractory MM in the U.S. and Europe.  Recently, a small phase-II clinical trial reported an advantage in PFS for elo plus pomalidomide (pom)/dex compared to pom/dex alone and resulted in licensing of this novel triplet combination, but clinical experience is still limited.  These researchers analyzed the safety and efficacy of elo/pom/dex in a "real world" cohort of patients with advanced MM.  They queried the data-bases of the university hospitals of Würzburg and Vienna.  These investigators identified 22 patients with a median number of 5 LoTs who received elo/pom/dex before licensing within an early access program.  Patients received a median number of 5 4-week treatment cycles.  Median PFS was 6.4 months with 12-month and 18-month PFS rates of 35 % and 28 %, respectively.  The ORR was 50 % and 64 % of responding patients who achieved a longer PFS with elo/pom/dex compared to their most recent line of therapy.  Objective responses were also observed in 5 patients who had been pre-treated with pomalidomide.  Low tumor burden was associated with improved PFS (13.5 months for patients with ISS stage I/II at study entry versus 6.4 months for ISS III), although this difference did not reach statistical significance.  No infusion-related reactions were reported; the most frequent grade-3/4 adverse events (AEs) were neutropenia and pneumonia.  The authors concluded that Elo/pom/dex was an active and well-tolerated regimen in highly advanced MM even after pre-treatment with pomalidomide.

Warnings and Precautions

  • Infusion related reactions: Empliciti (elotuzumab) can cause infusion related reactions. Majority of the infusion related reactions occur with the first administration. Empliciti (elotuzumab) should be administered with pre‐infusion medications including intravenous corticosteroids, oral antipyretics, and an oral or intravenous anthistamine.
  • Infections: Infections were reported in majority of patients. Patients should be monitored for infections accordingly and treated immediately.
  • Second primary tumors: Second primiary tumors have been reported in the clinical trials. Patients should be monitored for the development of second primary tumors.
  • Hepatotoxicity: Elevations in transaminases have been reported in clinical trials. Patients should have liver enzymes monitored routinely. Interrupt Empliciti (elotuzumab) therapy if liver enzymes are Grade 3 or higher.
  • Safety and efficacy in pregnancy has not been evaluated.
  • There is no information concerning presence of Empliciti (elotuzumab) in human milk, the outcomes on breastfed infant, or the outcomes on production of milk.
  • Safety and efficacy in pediatric patients has not been evaluated.

Experimental Indications

There are 2 clinical trials on elotuzumab for the treatment of other malignancies --
  1. a phase-I trial: “Ph I Trial of NAM NK Cells and IL-2 for Adult Pts With MM and NHL” (This study is not yet open for participant recruitment; last verified January 2017); and
  2. a phase-II trial: “Lenalidomide, Dexamethasone, and Elotuzumab With or Without Cyclophosphamide in Treating Patients With Relapsed Primary Amyloidosis” (This study is currently recruiting participants; last verified September 2017).

Newly Diagnosed Multiple Myeloma

Radhakrishnan and associates (2017) stated that treatment of MM has undergone significant change in the past 10 years with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches.  Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells.  These investigators reviewed the pre-clinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory MM.  Although pre-clinical data looked very promising, elotuzumab monotherapy did not result in objective clinical responses in patients with relapsed/refractory multiple myeloma.  However, combination treatment with immunomodulators and proteasome inhibitors resulted in substantial clinical activity in relapsed/refractory MM.  The authors concluded that ongoing clinical trials are examining the role of elotuzumab in newly diagnosed MM in combination with standard treatment as well as in the maintenance setting after autologous stem cell transplant.

Kubo and colleagues (2020) stated that novel therapies are needed for patients with newly diagnosed MM (NDMM).  Elotuzumab plus lenalidomide and dexamethasone (ELd) is FDA-approved for the treatment of RRMM.  In a Japanese phase-II clinical trial, these researchers evaluated ELd versus lenalidomide and dexamethasone (Ld) in patients with NDMM who were ineligible for stem cell transplantation (SCT).  Elotuzumab infusion was accelerated to 5 ml/min by dose 3, cycle 1, allowing most subsequent infusions to be completed within 1 hour.  The primary end-point was ORR in the ELd arm; secondary end-points were the difference in ORR between treatments, and PFS.  Patients were randomized to ELd (n = 40) or Ld (n = 42); median number of treatment cycles was 13 (ELd) and 12 (Ld).  In the ELd arm, ORR was 88 % [70 % CI: 80 to 93].  The estimated difference in ORR between treatments was 13 % (95 % CI: - 4 to 30) in favor of ELd; PFS data were immature.  Safety was consistent with previous findings of ELd in Japanese patients with RRMM.  No infusion reactions occurred at the maximum rate of 5 ml/min, which was used in 89 % of elotuzumab infusions.  The authors concluded that ELd may be an effective, well-tolerated front-line treatment for patients with NDMM ineligible for SCT.

Smoldering Multiple Myeloma

Smoldering multiple myeloma is an asymptomatic clonal plasma cell disorder (Rajkumar, et al., 2015). Smoldering multiple myeloma is distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma.

Jagannath and colleagues (2018) noted that smoldering MM (SMM) is associated with increased risk of progression to MM within 2 years, with no approved treatments.  Elotuzumab has been shown to promote natural killer (NK) cell stimulation and antibody-dependent cellular cytotoxicity (ADCC) in-vitro.  CD56dim (CD56dim /CD16+ /CD3- /CD45+ ) NK cells represent the primary subset responsible for elotuzumab-induced ADCC.  In a phase-II, non-randomized clinical trial, patients with SMM received elotuzumab 20 mg/kg intravenously (cycle 1: days 1, 8; monthly thereafter) or 10 mg/kg (cycles 1, 2: weekly; every 2 weeks thereafter).  The primary end-point was the relationship between baseline proportion of bone marrow-derived CD56dim NK cells and maximal M protein reduction; secondary end-points included ORR and PFS.  A total of 15 patients received 20 mg/kg and 16 received 10 mg/kg; combined data were presented.  At database lock (DBL, September 2014), no association was found between baseline CD56dim NK cell proportion and maximal M protein reduction.  With minimum 28 months' follow-up (DBL: January 2016), ORR (90 % CI) was 10 % (2.7 to 23.2) and 2-year PFS rate was 69 % (52 to 81 %).  Upper respiratory tract infections occurred in 18/31 (58 %) patients; 4 (13 %) patients experienced infusion reactions, all grade 1 to 2.  The authors stated that elotuzumab plus lenalidomide/dexamethasone is under investigation for SMM.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :

HCPCS codes covered if selection criteria are met :

Elotuzumab (Empliciti) :

HCPCS codes covered if selection criteria are met:

J9176 Injection, elotuzumab, 1 mg

Other HCPCS codes related to the CPB:

J1094 Injection, dexamethasone acetate, 1 mg
J1100 Injection, dexamethasone sodium phosphate, 1mg
J8540 Dexamethasone, oral, 0.25 mg
J9041 Injection, bortezomib, 0.1 mg
J9047 Injection, carfilzomib, 1 mg

ICD-10 codes covered if selection criteria are met:

C90.02 Multiple myeloma in relapse

ICD-10 codes not covered for indications listed in the CPB:

C82.00 - C82.09 Follicular lymphoma
C83.00 - C83.09 Small cell B-cell lymphoma
C83.10 - C83.19 Mantle-cell lymphoma
C83.30 - C83.39 Diffuse large B-cell lymphoma
C83.50 - C83.59 Lymphoplasmacytic diffuse lymphoma
C85.10 - C85.99 Other and unspecified types of non-Hodgkin lymphoma
C90.00 - C90.01 Multiple myeloma not having achieved remission and in remission [not covered for newly diagnosed multiple myeloma and smoldering multiple myeloma]
E85.0 - E85.9 Amyloidosis

The above policy is based on the following references:

  1. Ashjian E, Redic K. Multiple myeloma: Updates for pharmacists in the treatment of relapsed and refractory disease. J Oncol Pharm Pract. 2016;22(2):289-302.
  2. Bristol-Myers Squibb. Prescribing Information. Empliciti (elotuzumab) for injection. Revised: 5/2017. Available at: https://packageinserts.bms.com/pi/pi_empliciti.pdf.
  3. Bristol-Myers Squibb Company. Empliciti (elotuzumab) for injection, for intravenous use. Prescribing Information. Princeton, NJ: Bristol-Myers Squibb Company; revised November 2018.
  4. Bristol-Myers Squibb Company. Empliciti (elotuzumab) for injection, for intravenous use. Prescribing Information. Princeton, NJ: Bristol-Myers Squibb Company; revised October 2019.
  5. Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018;379(19):1811-1822.
  6. Dimopoulos MA, Lonial S, White D, et al. Elotuzumab, lenalidomide, and dexamethasone in RRMM: Final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 2020;10(9):91.
  7. Empliciti (elotuzumab) injection. Princeton, NJ: Bristol‐Myers Squibb Company; November 2015.
  8. Hose D, Schreder M, Hefner J, et al. Elotuzumab, pomalidomide, and dexamethasone is a very well tolerated regimen associated with durable remission even in very advanced myeloma: A retrospective study from two academic centers. J Cancer Res Clin Oncol. 2020 Jul 18 [Online ahead of print].
  9. Jagannath S, Laubach J, Wong E, et al. Elotuzumab monotherapy in patients with smouldering multiple myeloma: A phase 2 study. Br J Haematol. 2018;182(4):495-503.
  10. Kubo K, Hori M, Ohta K, et al. Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A randomized, open-label, phase 2 study in Japan. Int J Hematol. 2020;111(1):65-74.
  11. Lonial S, Dimopoulos M, Palumbo A, et al; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373(7):621-631.
  12. Lonial S, Kaufman J, Laubach J, Richardson P. Elotuzumab: A novel anti-CS1 monoclonal antibody for the treatment of multiple myeloma. Expert Opin Biol Ther. 2013;13(12):1731-1740.
  13. National Comprehensive Cancer Network (NCCN). Elotuzumab. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; 2018; 2019.
  14. National Comprehensive Cancer Network (NCCN). Multiple myeloma. NCCN Clinical Practice Guidelines in Oncology, Version 3.2016. Fort Washington, PA: NCCN; 2016.
  15. National Comprehensive Cancer Network (NCCN). Multiple myeloma. NCCN Clinical Practice Guidelines in Oncology, Version 1.2019. Fort Washington, PA: NCCN; 2019.
  16. National Comprehensive Cancer Network (NCCN). Multiple myeloma. NCCN Clinical Practice Guidelines in Oncology, Version 1.2020. Fort Washington, PA: NCCN; 2019.
  17. National Comprehensive Cancer Network (NCCN). Multiple myeloma. NCCN Clinical Practice Guidelines in Oncology, Version 2.2021. Fort Washington, PA: NCCN; 2020.
  18. National Institutes of Health. ClinicalTrials.gov. Lenalidomide, dexamethasone, and elotuzumab with or without cyclophosphamide in treating patients with relapsed primary amyloidosis. Last verified September 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03252600?term=elotuzumab&cntry1=NA%3AUS&draw=2&rank=6.
  19. National Institutes of Health. ClinicalTRials.gov. Phase I trial of NAM NK cells and IL-2 for adult patients with MM and NHL. Last verified January 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03019666?term=elotuzumab&cntry1=NA%3AUS&draw=4&rank=32.
  20. Radhakrishnan SV, Bhardwaj N, Steinbach M, et al. Elotuzumab as a novel anti-myeloma immunotherapy. Hum Vaccin Immunother. 2017;13(8):1751-1757.
  21. Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood. 2015;125(20):3069-3075.
  22. Rajkumar SV. Overview of the management of multiple myeloma. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed July 2018.
  23. Schmidt-Wolf IG, Straka C, Scheid C, et al. State of the art treatment of progressive or refractory multiple myeloma. Dtsch Med Wochenschr. 2014;139(41):2091-2095.
  24. U.S. Food and Drug Administration. FDA approves Empliciti, a new immune-stimulating therapy to treat multiple myeloma. Press Announcement. Silver Spring, MD: FDA; November 30, 2015. Available at:  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474684.htm. Accessed December 3, 2015.