The U.S. Food and Drug Administration has approved Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), marking the first approval of a second-line treatment for this aggressive cancer. The approval specifically covers patients with DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).
Addressing Critical Unmet Medical Need
DLBCL represents the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in lymph nodes, spleen, liver, bone marrow, or other organs. The disease presents significant clinical challenges, with approximately one in three patients not responding to initial therapy or relapsing thereafter. In the United States, approximately 10,000 patients are diagnosed annually with relapsed or refractory DLBCL who are not eligible for ASCT.
"The FDA approval of Monjuvi in combination with lenalidomide helps address an urgent unmet medical need for patients with relapsed or refractory DLBCL in the United States," said Hervé Hoppenot, Chief Executive Officer of Incyte.
Clinical Trial Results Drive Approval
The FDA approval was based on data from the MorphoSys-sponsored Phase 2 L-MIND study, an open-label, multicenter, single-arm trial investigating Monjuvi in combination with lenalidomide. The study enrolled adult patients with relapsed or refractory DLBCL who had received at least one but no more than three prior lines of therapy, including an anti-CD20 targeting therapy such as rituximab.
Results from the L-MIND study demonstrated an overall response rate (ORR) of 55%, meeting the primary endpoint. The response breakdown included a complete response rate of 37% and a partial response rate of 18%. The median duration of response, a key secondary endpoint, reached 21.7 months.
Professor Gilles Salles, Chair of the Clinical Hematology Department at the University of Lyon, France, and lead investigator of the L-MIND study, emphasized the significance of the approval: "The FDA approval of Monjuvi brings a new treatment option to patients in dire need across the United States. Today's FDA decision offers new hope for patients with this aggressive form of DLBCL who progressed during or after first-line therapy."
Safety Profile and Monitoring Requirements
The safety profile of Monjuvi includes several important considerations requiring careful monitoring. Warnings and precautions include infusion-related reactions occurring in 6% of patients, serious or severe myelosuppression, infections in 73% of patients, and embryo-fetal toxicity. Neutropenia led to treatment discontinuation in 3.7% of patients.
The most common adverse reactions occurring in 20% or more of patients included neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite. Specific blood count abnormalities included neutropenia in 50% of patients, thrombocytopenia in 18%, and anemia in 7%.
Mechanism of Action and Development History
Monjuvi is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody that incorporates an XmAb engineered Fc domain. The drug mediates B-cell lysis through apoptosis and immune effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).
MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor in 2010. The FDA had previously granted Fast Track and Breakthrough Therapy Designation for the combination of Monjuvi and lenalidomide in relapsed or refractory DLBCL. The Biologics License Application received Priority Review and was approved under the FDA's Accelerated Approval program.
Commercial Strategy and Patient Support
Monjuvi is expected to be commercially available in the United States shortly following the approval. MorphoSys and Incyte will co-commercialize the drug in the United States, while Incyte holds exclusive commercialization rights outside the United States.
The companies have launched My Mission Support, a patient support program offering financial assistance, ongoing education, and other resources to eligible patients prescribed Monjuvi in the United States. Jean-Paul Kress, Chief Executive Officer of MorphoSys, noted that "this approval marks an important step in MorphoSys' transformation into a fully integrated biopharmaceutical company."
Regulatory Status and Future Development
A marketing authorization application seeking approval of tafasitamab in combination with lenalidomide in the European Union has been validated by the European Medicines Agency and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL who are not candidates for ASCT.
The accelerated approval is contingent upon verification and description of clinical benefit in confirmatory trials. Tafasitamab continues to be clinically investigated as a therapeutic option in B-cell malignancies through ongoing combination trials.
