VERLen: Tafasitamab, Lenalidomide, plus Rituximab in Frontline Diffuse Large B-cell Lymphoma Patients over 80 Y/O or Older, A LYSA Phase 2 trial

Introduction: Standard of care in newly diagnosed elderly patients with diffuse large B-cell lymphoma (DLBCL) consists of reduced-dose immunochemotherapy (e.g., mini-CHOP or R-CVP). Results remain highly unsatisfactory. VERLen (NCT04974216) was a multicenter phase II study that evaluated efficacy and safety of tafasitamab, lenalidomide and rituximab (TLR) in treatment naive DLBCL patients over 80y. Methods: Patients ≥ 80 y.o. with newly diagnosed DLBCL (WHO2017 classification, all subtypes, IPI or stage) and deemed able to receive R-miniCHOP regimen (according to investigator) were eligible. Following a short pre-phase, patients received 12 cycles of TLR every 28 days. (Figure 1A). Patients who received at least one dose of Tafa and Len, with a proven CD20+ DLBCL were included in the efficacy set. The primary endpoint was an ORR superior to 60% with a targeted ORR of 75% (α one-sided of 10% and power of 80%). VERLen was an IIS trial sponsored by the LYSARC and funded by Incyte. Results: From Feb 2022 to April 2024, 71 patients were enrolled among whom 67 were included in the efficacy set and 68 in the safety set. Patients’ characteristics were: a median age of 84 years (range 80–91), an ECOG of 0–1 in 75%, creatinine clearance < 40 ml/min in 19% and hypo-albuminemia in 33% of patients; 83% had NOS DLBCL, 76% had a stage III/IV, age-adjusted-IPI was 2–3 in 58% of patients. Patients received a median of 10 cycles, with 46% of patients receiving the full course (12 cycles). The primary endpoint was met with an ORR at C3 of 71.6% (80% CI: 63.4%–78.9%), with 49.3% of CR. After a median follow-up of 16 months, the 12-month PFS and OS rates were 52% and 82% (Figure 1B), respectively. Among the 25 patients who relapsed or progressed during follow-up, 18 received R-mini-CHOP, achieving an ORR/CRR of 45%/35%. At the time of analysis, 14 deaths were reported; causes of death were: lymphoma (n = 6), toxicity of treatment (n = 2), concurrent illness (septic shock and intracranial hematoma) (n = 2), general physical deterioration (n = 1) and unknown cause (n = 3). Regarding Toxicities: Grade 3–4 neutropenia was observed in 44% of patients, despite G-CSF recommendation. Grade 3–4 infections occurred in 29% of patients. Serious adverse events occurred in 36 patients, of which 35% were due to an infection. Twenty-three patients (34%) permanently discontinued therapy during the induction phase due to: progressive disease (n = 12), adverse event (AE) (n = 4), death (n = 3), or withdrawal by the patient (n = 4). Conclusion: The VERLen study reached its endpoint and underlines the interest of theTLR combination in ≥ 80 y.o. patients with newly diagnosed DLBCL. As a chemo-free combination, TLR appears as an interesting alternative to chemotherapy, but toxicities do occur. Taken together, our results support further investigations of the TLR regimen and show that prospective trial in very elderly patients is feasible and needed to better design SOC.