Diffuse Large B-Cell Lymphoma (DLBCL)


Monjuvi® (tafasitamab-cxix) is an approved CD19-directed cytolytic antibody prescribed in combination with Revlimid® (lenalidomide) for the treatment of adult patients who have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified. This includes patients with DLBCL arising from low-grade lymphoma and those who are not eligible for autologous stem cell transplant (ASCT).1 The drug was approved under the US Food and Drug Administration (FDA) Accelerated Approval Program in July 2020; this means that the continuation of approval is contingent on the results of a confirmatory trial showing that Monjuvi provides a clinical benefit to these patients.2

Mechanism of Action

Monjuvi is a humanized, Fc-engineered monoclonal antibody that contains an immunoglobulin G1/2 hybrid Fc-domain with 2 amino acid substitutions to modify the Fc-mediated functions of the antibody. The drug targets and binds to CD19, which is a B cell-specific antigen expressed on the surface of pre-B and mature B lymphocytes and in several B-cell malignancies, including DLBCL.1,3 

Upon binding to CD19, Monjuvi mediates B-cell lysis through several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). This process results in the elimination of CD19-expressing B cells. In vitro studies in DLBCL tumor cells have demonstrated greater ADCC activity with a combination of Monjuvi and lenalidomide than with either Monjuvi alone or lenalidomide alone.1,

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Administration

Before starting the Monjuvi infusion, administer premedications, such as acetaminophen, histamine receptor antagonists, and/or glucocorticosteroids. The recommended dosage is 12 mg/kg administered as an intravenous infusion on exact days in each 28-day cycle. In the first cycle, Monjuvi should be given on days 1, 4, 8, 15, and 22. In cycles 2 and 3, Monjuvi should be administered on days 1, 8, 15, and 22. Starting with cycle 4, Monjuvi should be given on days 1 and 15.1 

Monjuvi should be administered in combination with lenalidomide 25 mg for a maximum of 12 cycles. Monjuvi should then be continued as a monotherapy until disease progression or unacceptable toxicity requires discontinuation.

Monjuvi should be administered in a facility with immediate access to emergency equipment and ability to manage infusion-related reactions.

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Adverse Reactions

The most common adverse reactions were fatigue, diarrhea, decreased appetite, cough, respiratory tract infection, thrombocytopenia, anemia, neutropenia, pyrexia, and peripheral edema.1 Adverse reactions are more serious in older patients (65 years or older) than in younger patients. 

Warnings and Precautions

Severe reactions may occur including infusion-related reactions (fever, chills, rash, flushing, dyspnea, and hypertension); serious or severe myelosuppression (including neutropenia, thrombocytopenia, and anemia); infections (including opportunistic infections); and embryo-fetal toxicity (fetal B-cell depletion). The treatment was discontinued in 3.7% of patients because of neutropenia.1 

Effective contraception is advised during treatment with Monjuvi and for a duration of 3 months following the last dose. Women are also advised not to breastfeed children during the same period of treatment and post-treatment. Use in pediatric patients is not recommended as the safety and efficacy of Monjuvi have not been established in this population. 1

Get full prescribing information for Monjuvi at MPR

Safety and Efficacy in Trials

L-MIND, an open-label, multicenter, single-arm phase 2 trial (NCT02399085),4 evaluated the safety and efficacy (antitumor activity) of Monjuvi in combination with lenalidomide followed by Monjuvi as monotherapy in adult patients with relapsed or refractory DLBCL who were previously treated with 1 to 3 systemic therapies (including at least one anti-CD20 therapy) and were not candidates for high-dose chemotherapy and subsequent ASCT.5

Patients received intravenous Monjuvi (12 mg/kg) in combination with oral lenalidomide (25 mg/d) for a maximum of 12 cycles of 28 days each, followed by Monjuvi monotherapy until disease progression or unacceptable toxicity. Results from the study showed an overall response rate of 55%, including a complete response rate of 37% and a partial response rate of 18%. The median duration of response was 21.7 months.2,5 

A long-term follow-up analysis of L-MIND was published in September 2021 that assessed the safety and efficacy after more than 35 months of treatment. It confirmed a long duration of response, meaningful overall survival rate, and well-defined safety profile with Monjuvi plus lenalidomide followed by Monjuvi monotherapy in patients who had relapsed or refractory DLBCL and were ineligible for ASCT.6

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References

  1. Monjuvi (tafasitamab-cxix). Highlights of prescribing information. MorphoSys. Revised June 2021. Accessed August 14, 2022.
  2. FDA Approves Monjuvi® (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). News release. Business Wire; July 31, 2020.
  3. Definition of tafasitamab-cxix. National Cancer Institute Drug Dictionary. Accessed August 14, 2022.
  4. A study to evaluate the safety and efficacy of lenalidomide with MOR00208 in patients with R-R DLBCL. ClinicalTrials.gov. March 2016. Updated September 29, 2021. Accessed August 14, 2022.
  5. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4
  6. Duell J, Maddocks KJ, González-Barca E, et al. Long-term outcomes from the phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021;106(9):2417-2426. doi:10.3324/haematol.2020.275958

Reviewed by Harshi Dhingra, MD, on 8/22/2022.

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