The FDA has approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide (Revlimid) and rituximab (Rituxan) for adult patients with relapsed or refractory follicular lymphoma, marking a significant advancement in treatment options for this chronic hematologic malignancy.
The regulatory decision was supported by compelling data from the phase 3 inMIND trial (NCT04680052), which enrolled 548 patients with relapsed or refractory follicular lymphoma. At a median follow-up of 14.1 months, patients treated with the tafasitamab-based combination (n = 273) achieved a median progression-free survival (PFS) of 22.4 months (95% CI, 19.2-not evaluable) compared to 13.9 months (95% CI, 11.5-16.4) for those receiving placebo plus lenalidomide and rituximab (n = 275) per investigator assessment (HR, 0.43; 95% CI, 0.32-0.58; P < .0001).
Enhanced Efficacy Across Assessment Methods
The trial's robust design included independent review committee assessment, which showed even more pronounced benefits. The median PFS was not reached (95% CI, 19.3-not evaluable) for the experimental arm versus 16.0 months (95% CI, 13.9-21.1) in the control arm (HR, 0.41; 95% CI, 0.29-0.56).
"Follicular lymphoma is generally an indolent yet chronic cancer that frequently recurs after treatment, making long-term disease control a critical objective," stated Christina Poh, MD, an assistant professor of medicine at the University of Washington and Fred Hutchinson Cancer Center. "The FDA approval of [tafasitamab] in combination with rituximab and lenalidomide marks a significant advancement, offering a chemotherapy-free option that has demonstrated a meaningful reduction in the risk of disease progression across a broad patient population, including those with high-risk disease."
Study Design and Patient Population
The double-blind, placebo-controlled, randomized inMIND study enrolled patients at least 18 years of age with histologically confirmed grade 1, 2, or 3a follicular lymphoma, nodal marginal zone lymphoma, splenic marginal zone lymphoma, or extranodal marginal zone lymphoma. Patients were required to have received at least one prior systemic anti-CD20 agent or chemoimmunotherapy and have documented relapsed, refractory, or progressive disease following prior systemic therapy.
The median number of prior lines of therapy was 1, with 25% of patients receiving 2 lines and 20% receiving 3 or more lines. Patients were randomly assigned to receive tafasitamab or placebo for 12 cycles, with all patients receiving rituximab for 5 cycles and lenalidomide for 12 cycles.
Safety Profile and Tolerability
Regarding safety, serious adverse effects were reported in 33% of patients in the tafasitamab arm, with serious infections occurring in 24% of patients. The most common adverse events reported with the tafasitamab-based regimen included respiratory tract infections, diarrhea, rash, fatigue, muscle and bone pain, constipation, and cough. The most common grade 3/4 laboratory abnormalities occurring in at least 20% of patients comprised decreased neutrophil count and decreased lymphocyte count.
Additional serious adverse events reported in at least 2% of patients included renal insufficiency (3.3%), second primary malignancies (2.9%), and febrile neutropenia (2.6%). Fatal adverse event reactions occurred in 1.5% of patients, attributed to COVID-19, sepsis, and adenocarcinoma.
Clinical Significance and Treatment Standard
"Patients living with relapsed or refractory follicular lymphoma have been waiting for new options that improve PFS without [a] substantial increase in [adverse events]. Based on the data from the inMIND trial of [tafasitamab], today's approval brings to this patient population the first CD19- and CD20-targeted immunotherapy combination and a potential new treatment standard," said Hervé Hoppenot, chief executive officer of Incyte.
Dosing and Administration
Tafasitamab is recommended at a dose of 12 mg/kg via intravenous infusion for a maximum of 12 cycles, in combination with lenalidomide and rituximab. The agent is neither indicated nor recommended for the treatment of relapsed or refractory marginal zone lymphoma outside of controlled clinical trials.
This approval represents the second US approval for tafasitamab, following its July 2020 accelerated approval in combination with lenalidomide for adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified who are not eligible for autologous stem cell transplant.
