Phase 3 study (inMIND) of tafasitamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma: Clinical characteristics and outcomes by age

Abstract Introduction: Incidence of follicular lymphoma (FL) increases with age and patients (pts) often relapse, requiring multiple lines of therapy. Tafasitamab (tafa), a humanized CD19-targeting monoclonal antibody (mAb), in combination with lenalidomide (len) + rituximab (R) was recently approved for treatment of adults with relapsed or refractory FL (R/R FL) in the US. At the primary analysis of inMIND (NCT04680052), an international, phase 3, double-blind, randomized, placebo (pbo)-controlled trial, tafa+len+R demonstrated a significant improvement in PFS in pts with R/R FL with a 57% reduction in the risk of progression or death and a safety profile as expected in the pt population (Sehn LH, et al. Blood. 2024;144[Suppl 2]:LBA1). This post hoc analysis evaluates efficacy and safety in pts enrolled in inMIND by age. Methods Eligible pts were aged ≥18 y with R/R CD19+ and CD20+ FL (grade 1-3A) and ECOG PS ≤2, who had 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. Pts with moderate renal insufficiency (CrCl ≥30 to <60 mL/min) were also eligible and received a reduced starting dose of len at 10 mg daily. Analyses included PFS by investigator (primary endpoint) and safety in pts <65 y and ≥65 y, and in pts <75 y and ≥75 y. Results Overall, 548 pts were randomized to the tafa arm (n=273) or pbo arm (n=275). Of the total pts enrolled in both treatment arms, 50% were <65 y (tafa, n=137; pbo, n=139), 50% were ≥65 y (tafa, n=136; pbo, n=136), 80% were <75 y (tafa, n=219; pbo, n=221), and 20% were ≥75 y (tafa, n=54; pbo, n=54). Baseline characteristics were generally similar between the tafa and pbo arms within age categories; median time since FL diagnosis (<65 y, 4.6 y and ≥65 y, 6.4 y; <75 y, 5.1 y and ≥75 y, 6.7 y) and proportions of pts with FLIPI score ≥3 (<65 y, 40% and ≥65 y, 65%; <75 y, 50% and ≥75 y, 64%) were higher in pts ≥65 y vs <65 y and ≥75 y vs <75 y. Proportions of pts with CrCl 30 to <60 mL/min were 5% and 34% in pts <65 y and ≥65 y and 11% and 52% in pts <75 y and ≥75 y, respectively. For pts <65 y, median investigator-assessed PFS was not reached with addition of tafa vs 12.0 months with pbo (hazard ratio [HR] [95% CI] 0.35 [0.22, 0.55]), and for pts ≥65 y was 20.0 months with tafa vs 15.0 months with pbo (HR [95% CI] 0.53 [0.35, 0.80]). Improvements were also observed in pts <75 y and ≥75 y: median investigator-assessed PFS was 23.6 months with addition of tafa vs 14.4 months with pbo (HR [95% CI] 0.44 [0.31, 0.61]) for pts <75 y, and 15.0 months with addition of tafa vs 13.0 months with pbo (HR [95% CI] 0.58 [0.30, 1.12]) in pts ≥75 y. The small number of pts ≥75 y limits interpretation of these data. TEAEs were reported for >98% of pts in the tafa or pbo arm across age subgroups. Grade 3 or 4 TEAEs were reported for 66% of pts <65 y in the tafa arm and 65% of pts in the pbo arm, and for 76% of pts ≥65 y in the tafa arm and 75% of pts in the pbo arm. Serious TEAEs were reported for 34% of pts <65 y in the tafa arm and 30% of pts in the pbo arm, and for 39% of pts ≥65 y in the tafa arm and 34% of pts in the pbo arm. Fatal TEAEs occurred in 1 pt (1%) <65 y in both the tafa and pbo arms and in 5 pts (4%) ≥65 y in both the tafa and pbo arms. Tafa or pbo discontinuations due to TEAEs were recorded for 10% and 6% of pts <65 y, and for 12% and 8% of pts ≥65 y in the tafa and pbo arms, respectively. Grade 3 or 4 TEAEs were reported for 69% and 68% of pts <75 y and for 80% and 74% of pts ≥75 y in the tafa and pbo arms, respectively. Serious TEAEs were reported for 35% of pts <75 y in the tafa arm and 28% of pts in the pbo arm, and for 41% of pts ≥75 y in the tafa arm and 44% of pts in the pbo arm. Fatal TEAEs occurred in 4 pts (2%) and 2 pts (4%) <75 y, and in 3 pts (1%) and 3 pts (6%) ≥75 y in the tafa and pbo arms, respectively. Tafa or pbo discontinuations due to TEAEs were reported for 10% of pts <75 y in the tafa arm and 6% of pts in the pbo arm, and for 17% of pts ≥75 y in the tafa arm and 11% of pts in the pbo arm. Data on tafa and len dose reduction will be presented. Conclusions This analysis confirms that tafa+len+R reduced risk of progression or death measured by PFS irrespective of pt age, including older pts up to 88 y and with moderate renal insufficiency. The safety profile was manageable across older and younger pts with toxicities as expected for the pt population.