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7066 Background: Despite advanced treatments, including chimeric antigen receptor therapy (CAR-T), a significant proportion of patients succumb to relapsed and refractory diffuse large B cell lymphoma (R/R DLBCL). In vitro experiments suggest synergism between BTK inhibitor (BTKi) and T-cell engager, we initiated a multicenter trial of poseltinib and glofitamab in combination with lenalidomide in R/R DLBCL. Methods: This is a phase II, open label, single arm study aiming to enroll 76 participants with adult R/R DLBCL patients (NCT05335018). Patients refractory to frontline therapy or those who failed more than two lines of therapies were enrolled. Previous anti-CD19 CAR-T was allowed, while previous CD20 T-cell engager was not permitted. Participants received glofitamab (In cycle 1, dose is increased weekly from 2.5mg to 10mg, and after cycle 2, 30mg is administered on Day 1), lenalidomide (20mg daily from Day 1-14), and poseltinib (40mg twice daily from Day 1-21) (GPL) every 3 weeks for a total of 12 cycles(induction). Maintenance with poseltinib and lenalidomide for 17 cycles were given to patients after induction period. The primary endpoint is overall response rate (ORR), with secondary endpoints including duration of response (DoR), complete response rate (CRR), progression free survival (PFS), overall survival (OS), and incidence of treatment related adverse events. Results: No safety signals were observed in the safety cohort (n=6, 3+3 design). As of November 2023, 37 patients (median age 71) have been treated with GPL, with a median follow up duration of 3.6 months. In prior lines of therapy, 13 patients (35.1%) received treatment more than 2, and 26 patients (70.3%) were with Ann Arbor stage III/IV and 7 patients (18.9%) were refractory to frontline treatment. Previously, 3 patients (8.1%) received CAR-T. Out of 28 evaluable patients, ORR was 89.3%, with CRR of 42.9%. Six-month OS and PFS rate were 81% and 55%. DoR at 6 months was 66%. Neutropenia (45.9%) was the most common grade(gr) 3-4. Three patients (8.1%) died of gr5. There was 1 case (2.7%) of gr3 atrial fibrillation and gr1 bleeding. No incidence of gr3 or above liver/renal toxicity were observed. Overall, 3 patients (8.1%) discontinued GPL treatment due to toxicity, and cytokine release syndrome was observed in 7 patients (18.9%) and only 2 patients (5.4%) were gr3-4. Conclusions: Interim analysis indicates that the GPL regimen is an effective and safe regimen for R/R DLBCL patients. High response rates observed support further investigation of GPL for potential synergism between T-cell engagers and BTKi. This multicenter study is actively recruiting patients and is set to complete enrollment within this year. Clinical trial information: NCT05335018 . Table: see text
Koh et al. (Sat,) studied this question.