Phase 3 study (inMIND) of tafasitamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma: Clinical characteristics and outcomes of high-risk patients

Abstract

Abstract Introduction: Despite initial response to first-line therapy, most patients (pts) with follicular lymphoma (FL) experience relapse requiring multiple lines of therapy. A need exists for treatments that are effective in all pts including those with high-risk disease. Tafasitamab (tafa) is a humanized CD19-targeting monoclonal antibody (mAb) recently approved in combination with lenalidomide (len) + rituximab (R) for adults with relapsed or refractory FL (R/R FL) in the US. inMIND (NCT04680052), an international, phase 3, double-blind, randomized, placebo (pbo)-controlled trial, evaluated the efficacy and safety of adding tafa to len+R in pts with R/R FL or marginal zone lymphoma. Tafa added to len+R resulted in significant improvement in PFS with a 57% reduction in the risk of progression or death and a manageable safety profile in pts with R/R FL; benefit was observed regardless of refractoriness to prior anti-CD20 mAb therapy or POD24 status (Sehn LH, et al. Blood. 2024;144[Suppl 2]:LBA1). This post hoc analysis evaluates efficacy outcomes in additional subgroups of pts with high-risk FL from inMIND. Methods: Pts were aged ≥18 y with R/R CD19+ and CD20+ FL (grade 1-3A) and ECOG PS ≤2, and must have received ≥1 prior systemic therapy including an anti-CD20 mAb. Pts were randomized 1:1 to receive tafa 12 mg/kg IV or pbo with standard dosing of len+R for up to 12×28-day cycles. Efficacy outcomes including PFS by investigator (primary endpoint; PFS was confirmed by IRC [data not shown]), PET-CR rate (FDG-avid population), ORR, and TTNT were assessed in pts with bulky disease (≥7 cm diameter), refractory to chemoimmunotherapy (CIT: including anti-CD20+CHOP; anti-CD20+bendamustine; anti-CD20+CVP) eg, SD or PD or achieving a response lasting <6 months in at least 1 prior line, and by high FLIPI score 3-5 or low/intermediate FLIPI score 0-2 (data not shown) and FL grade 3A or FL grade 1/2 (data not shown). Results: 548 pts with R/R FL were randomized in inMIND to the tafa arm (n=273) or pbo arm (n=275); overall, baseline characteristics were well balanced between treatment arms (Sehn LH, et al. Blood. 2024;144[Suppl 2]:LBA1). Of the pts enrolled in the study, 454 (83%) met ≥1 GELF criterion, 207 (38%) had bulky disease, 185 (34%) were CIT refractory, 287 (52%) had FLIPI score 3-5, and 138 (25%) had FL grade 3A disease; these characteristics were similar in the tafa and pbo arms. In pts with bulky disease, median investigator-assessed PFS was improved with addition of tafa vs pbo (22.3 months vs 13.0 months; hazard ratio [HR] [95% CI] 0.46 [0.28, 0.74]). PET-CR rate (51.1% vs 32.0%; odds ratio [OR] [95% CI] 2.2 [1.20, 3.86]), ORR (83.7% vs 66.1%; OR [95% CI] 2.3 [1.20, 4.57]), and median TTNT (not reached [NR] vs NR; HR [95% CI] 0.30 [0.16, 0.56]; Kaplan-Meier [K-M] estimate of TTNT at 2 years: 79% vs 50%) were also improved in pts with bulky disease with addition of tafa vs pbo. Among CIT-refractory pts, median investigator-assessed PFS was 14.8 months vs 8.3 months with addition of tafa vs pbo (HR [95%CI] 0.42 [0.27, 0.65]). Improvements were also observed with addition of tafa vs pbo in PET-CR rate (44.0% vs 20.7%; OR [95% CI] 3.2 [1.57, 6.47]), ORR (72.6% vs 60.0%; OR [95% CI] 1.8 [0.92, 3.35]), and median TTNT (27.8 months vs 13.4 months; HR [95% CI] 0.53 [0.33, 0.85]; K-M estimate of TTNT at 2 years: 58% vs 33%) in CIT refractory pts. Addition of tafa to len+R improved investigator-assessed PFS in pts with high FLIPI score 3-5: median PFS was 19.2 months with tafa vs 11.2 months with pbo (HR [95% CI] 0.43 [0.30, 0.62]); higher PET-CR rate (48.4% vs 33.8%; OR [95% CI] 1.9 [1.14, 3.12]), ORR (81.0% vs 70.0%; OR [95% CI] 1.9 [1.09, 3.42]), and median TTNT (NR vs 19.5 months; HR [95% CI] 0.50 [0.32, 0.76]; K-M estimate of TTNT at 2 years: 68% vs 49%) were also observed with addition of tafa vs pbo. Similarly, investigator-assessed PFS was improved with addition of tafa vs pbo in pts with FL grade 3A: median PFS was 24.0 months vs 13.9 months (HR [95% CI] 0.32 [0.17, 0.61]); addition of tafa vs pbo also resulted in higher PET-CR rate (56.3% vs 38.5%; OR [95% CI] 2.0 [0.98, 3.93]), ORR (83.6% vs 73.2%; OR [95% CI] 2.0 [0.84, 4.75]), and median TTNT (NR vs 17.9 months; HR [95% CI] 0.27 [0.12, 0.59]; K-M estimate of TTNT at 2 years: 85% vs 49%). Conclusions: This analysis of pts with R/R FL enrolled in the inMIND study confirms that addition of tafa to len+R improved all efficacy outcomes assessed in pts with high-risk disease.