The addition of Monjuvi (tafasitamab-cxix) to Revlimid (lenalidomide) and Rituxan (rituximab) has demonstrated a significant improvement in progression-free survival (PFS) for patients with relapsed or refractory follicular lymphoma (FL), according to the phase 3 inMIND trial presented at the 2024 American Society of Hematology (ASH) Annual Meeting. The study's findings suggest a potential new standard of care for this patient population.
Key Findings from the inMIND Trial
The inMIND trial, a randomized, double-blind, placebo-controlled phase 3 study, evaluated the efficacy and safety of Monjuvi in combination with Revlimid and Rituxan in patients with relapsed or refractory FL who had received one or more prior lines of systemic therapy. A total of 548 patients were randomized 1:1 to either the experimental arm (Monjuvi + Rituxan + Revlimid) or the control arm (placebo + Rituxan + Revlimid).
At a median follow-up of 14.1 months, the median investigator-assessed PFS was 22.4 months in the Monjuvi arm compared to 13.9 months in the placebo arm (HR, 0.43; 95% CI: 0.32, 0.58; P < 0.0001). This represents a 57% reduction in the risk of disease progression or death with the addition of Monjuvi. According to independent review committee (IRC) assessment, the median PFS was not yet reached with the triplet versus 16 months with the doublet.
Efficacy Across Subgroups
Dr. Laurie H. Sehn, lead study author from BC Cancer Centre for Lymphoid Cancer, noted that the benefit of the Monjuvi combination was observed across all pre-specified subgroups, including patients with POD24 (progression of disease within 24 months of initial diagnosis) and those refractory to prior anti-CD20 monoclonal antibodies. In patients with POD24, the median PFS was 19.2 months with the triplet versus 11.3 months with the doublet. In patients without POD24, the median PFS was 23.6 months versus 16 months with the triplet and doublet, respectively.
In patients who were refractory to anti-CD20 antibody therapy, the median PFS was 15 months in the investigational arm versus 8.6 months in the control arm. In patients who were not refractory to anti-CD20 antibody therapy, the median PFS was 24 months versus 18.2 months with the investigational and control regimens, respectively.
Response Rates and Duration
The study also demonstrated improved response rates with the Monjuvi combination. The positron emission tomography complete response rate (PET-CR) was 49.4% in the Monjuvi arm versus 39.8% in the placebo arm (P=0.0286). The objective response rate (ORR) was 83.5% in the triplet arm versus 72.4% in the doublet arm (P=0.0014).
Furthermore, the median duration of response (DOR) was 21.2 months with the triplet versus 13.6 months with the doublet. The median time to next treatment (TTNT) was not reached with the triplet versus 28.8 months with the doublet.
Safety Profile
The safety profile of the Monjuvi combination was manageable and consistent with the known toxicities of the individual agents. Common treatment-emergent adverse events (TEAEs) included neutropenia, diarrhea, COVID-19, and constipation. Grade 3 or 4 TEAEs were similar between the treatment arms. Deaths occurred in 5.5% of patients in the Monjuvi arm versus 8.5% in the placebo arm.
Implications for Treatment
Follicular lymphoma is the most common indolent form of B-cell non-Hodgkin lymphoma, accounting for approximately 20% of NHL cases. Relapsed or refractory FL has a progressively worsening prognosis with each subsequent relapse, highlighting the need for more effective treatment options. The current standard of care for relapsed/refractory FL includes immunotherapy regimens, but the duration of response remains limited.
The inMIND trial results suggest that the combination of Monjuvi, Revlimid, and Rituxan represents a potential new standard of care for patients with relapsed/refractory FL. As Dr. Steven Stein, Chief Medical Officer of Incyte, stated, "These data... show the potential of [Monjuvi] in combination with [Revlimid] and [Rituxan] to become a new standard of care for these patients."
Incyte plans to file a supplementary Biologics License Application with the FDA by the end of 2024 for the treatment of patients with R/R FL who have failed prior systemic anti-CD20 immunotherapy or chemo-immunotherapy.
