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Monjuvi plus Revlimid and Rituxan demonstrated improved progression-free survival for patients with relapsed or refractory follicular lymphoma.
For patients with relapsed or refractory follicular lymphoma, Monjuvi (tafasitamab-cxix) in addition to Revlimid (lenalidomide) and Rituxan (rituximab) led to a 57% reduction in the risk of disease progression or death versus the placebo plus Revlimid and Rituxan, according to findings from a phase 3 trial that were presented at the 2024 ASH Annual Meeting.
At a median follow-up of 14.1 months, the median investigator-assessed progression-free survival (PFS) was 22.4 months with the triplet (273 patients) versus 13.9 months with Revlimid and Rituxan alone (275 patients).
According to independent review committee (IRC) assessment, the median PFS was not yet reached with the triplet versus 16 months with the doublet.
“The inMIND phase 3 study met its primary end point of prolonging PFS in relapsed/refractory follicular lymphoma,” Dr. Laurie H. Sehn, lead study author of BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, in Vancouver, Canada, said in a presentation of the data. “Benefit was observed in all prespecified subgroups, including patients with POD24 [progression of disease within 24 months of initial diagnosis], [those who were] refractory to prior anti-CD20 monoclonal antibodies, and [those] receiving multiple prior lines of therapy.”
Progression-free survival (PFS): time patients live without their cancer worsening or spreading.
Objective response rate (ORR): patients who responded partially or completely to treatment.
Intravenous: treatment given through the vein.
Neutropenia: low white blood cell count.
Thrombocytopenia: low platelet count.
Additional efficacy findings from the subgroup analysis also illustrated a PFS benefit favoring the investigational regimen regardless of POD24 status and refractoriness to anti-CD20 antibody therapy. 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.
With respect to response in the FDG-avid population the PET-CR rate was 49.4% in the investigational arm (251 patients) versus 39.8% in the control arm (254 patients). In the intention-to-treat population, the objective response rate (ORR) was 83.5% in the triplet arm versus 72.4% in the doublet arm.
Additional efficacy findings demonstrated that 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.
“The safety profile was manageable and consistent with expected toxicities with these agents,” Sehn said, turning to the regimen’s toxicity profile.
Some of the most common any-grade treatment-emergent adverse effects (TEAEs, side effects) in the Monjuvi and placebo arms, respectively, included neutropenia (48.5%; 45.2%), diarrhea (37.6%; 28.3%), COVID-19 (31.4%; 23.5%), constipation (29.2%; 24.6%), rash (21.9%; 21.3%) and fatigue (21.2%; 15.8%). The most common grade 3 (severe) or 4 (life-threatening) TEAEs in the Monjuvi and placebo arms, respectively, included neutropenia (39.8%; 37.5%), pneumonia (8.4%; 5.1%), thrombocytopenia (6.2%; 7.4%) and decreased neutrophil (white blood cell) count (5.8%; 6.6%), among others.
Sehn stated that Monjuvi and placebo dose interruptions or discontinuations because of TEAEs were similar between treatment arms, as were discontinuations for Revlimid.
Deaths occurred in 5.5% (15 patients) of patients in the investigational arm versus 8.5% (23 patients) of those in the placebo arm.
Most patients with follicular lymphoma will require more than one line of therapy, and although immunotherapy is a preferred regimen for patients with relapsed or refractory disease, the DOR of these agents remains limited.
The combination of Revlimid and Rituxan has been an FDA-approved regimen for patients with previously treated follicular lymphoma since 2018. The approval was based on data from the phase 3 AUGMENT trial, which showed an improvement in PFS versus Rituxan alone. Monjuvi is a CD19-directed monoclonal antibody that induces direct cytotoxic effects and improves NK cell and macrophage immune-mediated mechanisms.
A total of 548 patients were randomly assigned to treatment with Monjuvi (273 patients) or placebo (275 patients), and 51 (18.7%) and 42 (15.3%) remain on treatment, respectively. A total of 244 (89.4%) and 229 (83.3%) patients in the investigational and control arms, respectively, remain ongoing in the study. At the time of the analysis the median number of cycles received was 12 with Monjuvi versus 11 with placebo.
To be eligible for enrollment patients at least 18 years of age needed to have grade 1 to 3A follicular lymphoma or MZL and received at least one prior line of therapy, including an anti-CD20 monoclonal antibody. An ECOG performance status of 0 to 2 and no prior exposure to Revlimid plus Rituxan were also required.
Following confirmation of eligibility patients were randomly assigned to the experimental or control arm. In the experimental arm patients received 12 milligrams per kilogram (mg/kg) of intravenous (IV) Monjuvi every week for the first three cycles followed by every two weeks for cycles four through 12; plus 20 mg per day of oral Revlimid on days 1 to 21 for 12 cycles; and 375 mg per square meter of IV Rituxan once weekly for the first cycle and every four weeks for cycles two through five. In the control arm patients received IV placebo in the same schedule as Monjuvi, plus Revlimid and Rituxan via the same dosing schedule as the experimental arm.
“This study is the first to validate the approach of combining two antibodies for the treatment of patients with follicular lymphoma. [Monjuvi] plus [Revlimid] and [Rituxan] can be administered in community as well as academic settings and represents a potential new standard of care for patients with relapsed/refractory follicular lymphoma,” Sehn said in conclusion.
References:
“Tafasitamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma: results from a phase 3 study (inMIND).” By Dr. Laurie H. Sehn, Blood.
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