Tafasitamab-cxix (Monjuvi)

Number: 0979

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses tafasitamab-cxix (Monjuvi) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of tafasitamab-cxix (Monjuvi) is required of all Aetna participating providers and members in applicable plan designs. For precertification of tafasitamab-cxix (Monjuvi), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   B-Cell Lymphomas

   Aetna considers tafasitamab-cxix (Monjuvi) medically necessary for the treatment of relapsed or refractory B-cell lymphomas when all of the following criteria are met:

   1. The member has one of the following B-cell lymphoma subtypes:

      1. Human immunodeficiency virus (HIV)-related B-cell lymphoma (including HIV-related diffuse large B-cell lymphoma (DLBCL), primary effusion lymphoma, HIV-related plasmablastic lymphoma, and human herpesvirus-8 (HHV8)-positive DLBCL); or
      2. Histologic transformation of indolent lymphomas to DLBCL; or
      3. Monomorphic post-transplant lymphoproliferative disorders (PTLD) (B-cell type); or
      4. DLBCL (including DLBCL arising from low grade lymphoma and DLBCL not otherwise specified); or
      5. High-grade B-cell lymphomas (HGBLs); and 
   2. The member is not eligible for an autologous stem cell transplant; and
   3. The requested medication will be used in combination with lenalidomide for up to a maximum of 12 cycles.

   Aetna considers all other indications as experimental investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of tafasitamab-cxix (Monjuvi) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen, and if the member has completed 12 cycles, the requested drug will be used as monotherapy.

Dosage and Administration

Tafasitamab-cxix (Monjuvi) is available for injection as 200 mg of tafasitamab-cxix lyophilized powder in a single-dose vial for reconstitution for intravenous infusion. Monjuvi should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions.

Diffuse Large B-cell Lymphoma

The recommended dose of Monjuvi is 12 mg/kg based on actual body weight administered as an intravenous infusion according to the dosing schedule in the table below.

Administer Monjuvi in combination with lenalidomide 25 mg for a maximum of 12 cycles, then continue Monjuvi as monotherapy until disease progression or unacceptable toxicity. Refer to lenalidomide prescribing information for lenalidomide dosage recommendations. 

Table: Dosing Schedule for Monjuvi

Cycle	Dosing Schedule
Cycle 1	Days 1, 4, 8, 15, and 22
Cycles 2 and 3	Days 1, 8, 15 and 22
Cycle 4 and beyond	Days 1 and 15

Note: Each treatment cycle is 28 days.

Source: Incyte, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96413 - 96417	Intravenous chemotherapy administration
HCPCS codes covered if selection criteria are met:
J9349	Injection, tafasitamab-cxix, 2 mg
Other HCPCS codes related to the CPB:
Lenalidomide - no specific code
ICD-10 codes covered if selection criteria are met:
C83.30 - C83.39	Diffuse large B-cell lymphoma
C83.80 - C83.89	Other non-follicular lymphoma [primary effusion lymphoma]
C85.10 - C85.19	Unspecified B-cell lymphoma [(AIDS)-related B-cell lymphoma]
D47.Z1	Post-transplant lymphoproliferative disorder (PTLD) [Monomorphic post-transplant lymphoproliferative disorders (PTLD)]

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Background

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

• Monjuvi, in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT).

Compendial Uses

B-cell lymphomas

• Human immunodeficiency virus (HIV)-related B-cell lymphoma
• Histologic transformation of indolent lymphomas to diffuse large B-cell lymphoma
• Monomorphic post-transplant lymphoproliferative disorders (B-cell type)
• Diffuse large B-cell lymphoma (DLBCL)
• High-grade B-cell lymphomas (HGBLs)

Tafasitamab-cxix is available as Monjuvi (Morphosys US Inc) and is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. Tafasitamab-cxix (Monjuvi) binds to CD19 antigen expressed on the surface of pre-B and mature B lymphocytes and on several B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL).which results in B-celly lysis through apoptosis and immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) (Morphsys US).

Per the prescribing information, tafasitamab-cxix (Monjuvi) carries the warnings and precautions:

• Infusion-related reactions: In the L-MIND study, infusion-related reactions happened in 6% of the 81 patients. Additionally, it was noted that 80% of infusion-related reactions happened during cycle 1 or 2.
• Myelosuppression: In the L-MIND study, grade 3 neutropenia happened in 25% of patients, thrombocytopenia in 12%, and anemia in 7%. Grade 4 neutropenia happened in 25% and thrombocytopenia in 6%.
• Infections: In the L-MIND study, 73% of the 81 patients experienced an infection.
• Embryo-fetal toxicity.

Per the prescribing information, the most common adverse reactions (≥20%) included neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.

Diffuse Large B-cell Lymphoma (DLBCL)

Non-Hodgkin lymphoma (NHL) is generally divided into T lymphocytes (T-cell) or B lymphocytes (B-cell). Diffuse large B-cell lymphoma is one of subtypes of B-cell lymphoma. Patients with relapsed or refractory DLBCL who are ineligible for autologous stem-cell transplantation have poor outcomes and few treatment options.

Salles et al. (2020) assessed the antitumour activity and safety of tafasitamab plus lenalidomide in the L-MIND study. The L-MIND study is a multicenter, open-label, single-arm, phase 2 study that evaluated tafasitamab plus lenalidomide in adults 18 years of age and older with histologically confirmed DLBCL, who relapsed or had refractory disease after previous treatment with one to three systemic regimens (with at least one anti-CD20 therapy), were not candidates for high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT), had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and had measurable disease at baseline. Patients received coadministered intravenous tafasitamab (12 mg/kg) and oral lenalidomide (25 mg/day) for up to 12 cycles (28 days each), followed by tafasitamab monotherapy (in patients with stable disease or better) until disease progression. The primary endpoint was the proportion of patients with an objective response (centrally assessed), defined as a complete or partial response according to the 2007 International Working Group response criteria for malignant lymphoma. Antitumour activity analyses are based on all patients who received at least one dose of both tafasitamab and lenalidomide. Safety analyses were based on all patients who received at least one dose of either study medication. Between Jan 18, 2016, and Nov 15, 2017, 81 patients were enrolled and received at least one dose of either study medication, and 80 received at least one dose of both tafasitamab and lenalidomide. Median follow-up was 13.2 months as of data cutoff on Nov 30, 2018. Forty-eight (60%) of 80 patients who received tafasitamab plus lenalidomide had an objective response: 34 (43%) had a complete response and 14 (18%) had a partial response. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (39 [48%] of 81 patients), thrombocytopenia (14 [17%]), and febrile neutropenia (ten [12%]). Serious adverse events occurred in 41 (51%) of 81 patients. The most frequently reported serious adverse events (in two or more patients) were pneumonia (five [6%]), febrile neutropenia (five [6%]), pulmonary embolism (three [4%]), bronchitis (two [2%]), atrial fibrillation (two [2%]), and congestive cardiac failure (two [2%]). The authors concluded that tafasitamab in combination with lenalidomide was well tolerated and resulted in a high proportion of patients with relapsed or refractory DLBCL ineligible for autologous stem-cell transplantation having a complete response. 

In May 2019, the L-MIND study reached its primary completion, in which, out of 71 patients with confirmed DLBCL, 55% reached an overall response rate (primary endpoint), including a complete response (CR) rate of 37% and a partial response rate (PR) of 18%. The median duration of response (mDOR) was 21.7 months (key secondary endpoint) (Morphosys AG, 2020b; Morphosys US, 2020).

On July 31, 2020, the FDA approved Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). Monjuvi was approved under accelerated approval by the U.S. FDA based on overall response rate (ORR) from the L-MIND study. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The FDA decision represented the first approval of a second-line treatment for adult patients who progressed during or after first-line therapy (Morphosys AG, 2020b).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials (Morphosys AG, 2020b).

Tafasitamab for the Treatment of B-Precursor Cell Acute Lymphoblastic Leukemia

Klisovic et al (2021) stated that B-precursor cell acute lymphoblastic leukemia (B-ALL) in adults is an aggressive and challenging condition, and patients with relapsed/refractory (R/R) disease following allogeneic stem cell transplantation (allo-SCT), or non-candidates for SCT, have a particularly poor prognosis.  In an open-label, single-arm, phase-IIa clinical trial, these investigators examined the activity of the Fc-modified anti-CD19 antibody tafasitamab in adults with R/R B-ALL.  Adults with R/R B-ALL received single-agent tafasitamab 12 mg/kg weekly for up to four 28-day cycles.  Patients with complete remission (with or without neutrophil/platelet recovery; complete remission [CR] or complete remission with incomplete count recovery [CRi]) after cycles 2, 3, or 4 could continue tafasitamab every 2 weeks for up to 3 further months.  The primary endpoint was ORR.  A total of 22 patients were treated (median of 2 prior lines of therapy; range of 1 to 8); 6 patients completed 2 cycles, and 2 of these patients responded for an ORR of 9 %; 16 patients (73 %) progressed before their 1st response assessment.  Responses lasted 8 and 4 weeks in the 2 patients with CR and minimal residual disease (MRD)-negative CRi, respectively.  Tafasitamab produced rapid B-cell/blast depletion in 21 of 22 (95.5 %) patients within 1 to 2 weeks of 1st administration.  Tafasitamab was well-tolerated, with the most frequent adverse events (AEs) being infusion-related reactions (59.1 %) and fatigue (40.9 %).  Grade-3 to grade-4 febrile neutropenia (22.7 %) was the most common hematologic AE.  The authors concluded that tafasitamab monotherapy was associated with clinical activity in a subset of patients with R/R B-ALL, including short-lasting CR and MRD-negative CRi.  Given its favorable tolerability profile, further development of tafasitamab in chemoimmunotherapy combinations and MRD settings should be examined.

Combined Tafasitamab and Idelalisib or Venetoclax for the Treatment of Chronic Lymphocytic Leukemia

Staber et al (2021) noted that patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) whose treatment failed with a Bruton's tyrosine kinase inhibitor (BTKi) have poor outcomes.  In a phase-II clinical trial, these investigators examined the effectiveness of tafasitamab plus idelalisib (cohort A) or venetoclax (cohort B) in patients with CLL previously treated with a BTKi.  A total of 24 patients were enrolled (cohort A: n = 11, median time on study, 7.4 months; cohort B: n = 13, median time on study, 15.6 months).  The most common treatment-emergent AE (TEAE) in cohort A was anemia (63.6 %) and in cohort B was infusion-related reaction (53.8 %).  The most common severe TEAE was neutropenia (cohort A: 45.5 %; cohort B: 46.2 %).  The best ORR was 90.9 % (cohort A) and 76.9 % (cohort B).  Undetectable MRD in peripheral blood was achieved in 2/8 (25 %) patients (cohort A) and 6/7 (85.7 %) patients (cohort B).  The authors concluded that the findings of this study suggested that anti-CD19 antibody-based combinations may be important in the treatment of patients with CLL.

Combined Tafasitamab and γδ T-Cell or Allogeneic NK Cell Therapy for the Treatment of B-Cell Non-Hodgkin's Lymphoma

Her et al (2022) stated that tafasitamab is an Fc-modified monoclonal antibody that binds to CD19, a cell-surface antigen that is broadly expressed on various types of B-cell NHL.  Antibody-dependent cellular cytotoxicity (ADCC), a key mode of action of tafasitamab, is mediated via the binding of tafasitamab's Fc region to FcγRIIIa receptors on immune effector cells and results in anti-tumor activity.  Despite the proven clinical activity of tafasitamab in combination with lenalidomide in the treatment of DLBCL, a higher number of immune cells in cancer patients may improve the activity of tafasitamab.  These researchers characterized 2 ex vivo-expanded FcγRIIIa receptor-expressing cell types-γδ T and MG4101 natural killer (NK) cells-as effector cells for tafasitamab in-vitro, and found that in the presence of these cells, tafasitamab was able to induce ADCC against a range of NHL cell lines and patient-derived cells.  These investigators also examined the concept of effector cell supplementation during tafasitamab treatment in-vivo by co-administering MG4101 NK cells in Raji and Ramos xenograft models of NHL.  Combined treatment of tafasitamab and allogeneic MG4101 NK cells in these models showed a survival benefit compared with tafasitamab or MG4101 monotherapy (Raji: 1.7- to 1.9-fold increase in lifespan; Ramos: 2.0- to 4.1-fold increase in lifespan).  The authors concluded that adoptive cell transfer of ex vivo-expanded allogeneic NK or autologous γδ T cells in combination with tafasitamab treatment may potentially be a promising novel approach to increase the number of immune effector cells and enhance the anti-tumor effect of tafasitamab.

Combined Tafasitamab and Venetoclax for the Treatment of B-Cell Malignancies

Vogiatzi et al (2022) noted that immunotherapy has evolved as a powerful tool for the treatment of B-cell malignancies and patient outcomes have improved by combining therapeutic antibodies with conventional chemotherapy.  Over-expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) is associated with a poor prognosis and increased levels have been described in patients with "double-hit" DLBCL, a subgroup of Burkitt´s lymphoma and pediatric ALL patients harboring a t(17;19) translocation.  These researchers showed that the addition of venetoclax (VEN), a specific Bcl-2 inhibitor, potently enhanced the effectiveness of the therapeutic anti-CD20 antibody rituximab (RTX), anti-CD38 daratumumab (DARA) and anti-CD19, named CD19-DE, a proprietary version of tafasitamab.  This was due to an increase in antibody-dependent cellular phagocytosis by macrophages as shown in-vitro and in-vivo in cell lines and patient-derived xenograft (PDX) models.  Mechanistically, double-hit lymphoma cells subjected to VEN triggered phagocytosis in an apoptosis-independent manner.  The authors concluded that this study identified the combination of VEN and therapeutic antibodies as a promising novel strategy for the treatment of B-cell malignancies.

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References