Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial
Mené sur 548 patients atteints d'un lymphome folliculaire récidivant ou réfractaire, cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du tafasitamab (un anticorps monoclonal ciblant CD19) à un traitement combinant lénalidomide et rituximab
Background: Follicular lymphoma is characterised by episodes of remission and relapse, with patients requiring multiple lines of therapy. Lenalidomide plus rituximab is a commonly used immunotherapy combination in patients with relapsed or refractory follicular lymphoma. We aimed to assess the efficacy and safety of adding tafasitamab, a CD19-targeted Fc-enhanced monoclonal antibody, to lenalidomide and rituximab in this setting.
Methods: This phase 3, double-blind, randomised, placebo-controlled trial (inMIND) was done in 210 centres (including community-based haematology clinics, major hospitals, and academic institutions) in North America, Europe, and the Asia–Pacific region. Adults with relapsed or refractory follicular lymphoma, who had received at least one previous line of systemic therapy, were eligible for enrolment and randomly assigned (1:1) to receive treatment with up to 12 cycles (28-day cycle length) of tafasitamab (12 mg/kg by intravenous infusion on days 1, 8, 15, and 22 of cycles 1–3 and days 1 and 15 of cycles 4–12) or placebo, both with lenalidomide (20 mg/day orally on days 1–21 of cycles 1–12) and rituximab (375 mg/m2 by intravenous infusion on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2–5). Treatment assignment was achieved via an interactive voice or web response system; patients, investigators, and the funder were masked until the primary analysis. Study endpoints were investigator assessed unless otherwise specified. The primary endpoint was progression-free survival in the intention-to-treat population of all randomised patients; safety was assessed in all randomised patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov (NCT04680052) and EUDRA-CT (2020–004407–13) and is active but no longer enrolling.
Findings: Between April 16, 2021, and Aug 10, 2023, a total of 817 patients were assessed for eligibility; 548 patients with relapsed or refractory follicular lymphoma were enrolled and randomly assigned to treatment with either tafasitamab (n=273) or placebo (n=275). 299 (55%) of all randomised patients were male and 249 (45%) were female. The addition of tafasitamab to lenalidomide and rituximab resulted in significantly lower risk of progression, relapse, or death versus placebo (median progression-free survival by investigator 22·4 months [95% CI 19·2 to not evaluable] in the tafasitamab group vs 13·9 months [11·5–16·4] in the placebo group; hazard ratio 0·43 [95% CI 0·32–0·58]; p<0·0001) in the planned primary analysis. Improvement in progression-free survival was confirmed by independent review committee. Adverse events were reported in 272 (99%) of 274 patients in the tafasitamab group and 270 (99%) of 272 patients in the placebo group. Most common adverse events occurring in either the tafasitamab group or placebo group were neutropenia (133 [49%] vs 123 [45%]) and diarrhoea (103 [38%] vs 77 [28%]). There were no deaths due to treatment-related adverse events in the tafasitamab group; two (1%) patients had fatal adverse events related to treatment in the placebo group.
Interpretation: The addition of tafasitamab to lenalidomide and rituximab resulted in a statistically significant and clinically meaningful improvement in progression-free survival, with an acceptable safety profile in patients with relapsed or refractory follicular lymphoma. This combination represents a potential new standard-of-care treatment.
The Lancet , résumé, 2025