Tafasitamab-cxix (Monjuvi)

Number: 0979

Policy

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 (Commercial), (866) 503-0857 (Medicare), or fax (866) 267-3277.

Aetna considers tafasitamab-cxix (Monjuvi) medically necessary for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma when all of the following criteria are met:

• The member is not eligible for an autologous stem cell transplant; and
• The requested medication will be used in combination with lenalidomide for up to a maximum of 12 cycles; and
• The B-cells must be CD19-positive as confirmed by testing or analysis.

Aetna considers continuation of tafasitamab-cxix therapy medically necessary for members requesting reauthorization for an indication listed above 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.

Aetna considers tafasitamab-cxix experimental and investigational for all other indications.

Dosing Recommendations

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

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: Morphosys US, 2020

Background

Tafasitamab-cxix (Monjuvi) is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody.

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

• 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).

The National Comprehensive Cancer Network Drugs & Biologics Compendium (NCCN, 2020) provide a category 2A recommendation for the following indications for tafasitamab-cxix:

• Used in combination with lenalidomide for treatment of histologic transformation to diffuse large B-cell lymphoma (DLBCL) without translocations of MYC and BCL2 and/or BCL6 in patients who are not candidates for transplant and have received

  • minimal or no chemoimmunotherapy prior to histologic transformation to DLBCL and have no response or progressive disease after chemoimmunotherapy (anthracycline- or anthracenedione-based regimens preferred unless contraindicated);
  • multiple prior therapies including 2 or more lines of chemoimmunotherapy for indolent or transformed disease;
    
    

• DLBCL: Second-line and subsequent therapy in combination with lenalidomide for partial response, no response, relapsed, progressive, or refractory disease in non-candidates for transplant;

• Histologic Transformation of Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma: Used in combination with lenalidomide in patients who are not candidates for transplant and have received

  • minimal or no chemoimmunotherapy prior to histologic transformation to diffuse large B-cell lymphoma and have no response or progressive disease after chemoimmunotherapy (anthracycline- or anthracenedione-based regimens preferred unless contraindicated)
  • multiple prior therapies including 2 or more lines of chemoimmunotherapy for indolent or transformed disease.

Warnings and precautions of tafasitamab-cxix includes infusion-related reactions, myelosuppression, infections (bacterial, fungal and viral infections can occur during and following therapy), and embryo-fetal toxicity (Morphosys US, 2020).

The most common adverse reactions (20% or greater) are neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite (Morphosys US, 2020).

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).

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 "+" :
Other CPT codes related to the CPB:
96413 - 96417	Intravenous chemotherapy administration
HCPCS codes covered if selection criteria are met:
C9070	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

The above policy is based on the following references: