Glofitamab plus R‐CHOP or polatuzumab vedotin‐R‐CHP is deliverable with high overall response in patients ≤65 years of age with high‐risk DLBCL: Interim analysis of COALITION

Background: Improved treatments are needed for patients (pts) with high-risk (HR) DLBCL. Intensification of R-CHOP has not improved outcomes. Furthermore, pts with HR disease are frequently excluded from trials due the need for rapid treatment initiation, an independent predictor of poor outcome. Glofitamab (glo) is a CD20/CD3 bispecific antibody achieving 39% complete remission (CR) rate R/R DLBCL (Dickinson, NEJM 2023). We present an interim analysis of an ongoing investigator-initiated, parallel-arm, phase I/II study of glo in combination with R-CHOP or polatuzumab vedotin (pola)-R-CHP in younger pts with HR DLBCL. Methods: Eligible pts include untreated DLBCL, age 18–65, and at least one HR feature: IPI ≥3, NCCN-IPI ≥4, or proven double-hit status. To minimise treatment delay, enrolment is allowed after 1 cycle of R-CHOP and ECOG <4 at baseline or <2 at C2 is permitted. Pts receive 5 cycles of glo (2.5 mg & 10 mg step-up in C2, 30 mg in C3-6) in combination with R-CHOP (Arm A) or Pola-R-CHP (Arm B), followed by 2 cycles of glo consolidation. Primary endpoints are safety, relative dose intensity (RDI) and rate of treatment discontinuation. Responses are evaluated after cycles 2, 4 and 6 and then 3–6 monthly. Adverse events (AEs) are graded using CTCAE V5.0, except cytokine-release syndrome (CRS) and neurotoxicity (ICANS) graded by ASTCT criteria. Results: 47 patients have received ≥1 dose of study treatment at Nov 1, 2022 (25 Arm A, 22 Arm B). 42 (89%) have de novo DLBCL and 5 (11%) have transformed indolent lymphoma. Median age was 52 years (range 24–65), IPI was ≥3 in 81%, and NCCN-IPI was ≥4 in 81%. The median TMTV was 673 cm3 (IQR 249–1221 cm3). Median time from diagnosis to first R-CHOP was 15 days (IQR 11–21.5). Grade (Gr) ≥3 AEs were seen in 10/25 (40%) (Arm A) and 11/21 (52%) (Arm B). There were no Gr 5 AEs. Febrile neutropenia was observed in 1/25 (4%) and 6/21 (29%) and CRS Gr 1 in 5/25 (20%) and 5/21 (24%), respectively. There was 1 episode of Gr 2 CRS in Arm A. Neuropathy was limited to Gr 1–2 in 11/25 (44%) and 5/21 (24%) respectively. No ICANS was observed. The RDI was ≥90% for cyclophosphamide, doxorubicin, pola, vincristine and glo in 93%, 93%, 100%, 76% and 88% of patients, respectively. There was 1 dose interruption of doxorubicin and 3 interruptions to glo, 2 for infection and 1 for rash. 41 treated pts had at least 1 efficacy assessment, with best overall response rate 100%. Of 25 pts who reached the end of induction (EOI) assessment, 19 (76%) demonstrated CR, 5 (20%) PR and 1 (5%) PD. At a median follow up of 3.7 months (mo), the estimated PFS at 6-mo was 91% (Figure). Of the 5 pts with PR at EOI, none has progressed with median follow up 6.1 mo. Encore Abstract - previously submitted to EHA 2023 The research was funded by: F Hoffman La Roche Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies, Ongoing Trials Conflicts of interests pertinent to the abstract. A. Minson Honoraria: Roche Research funding: Novartis, Roche Educational grants: Novartis N. Hamad Honoraria: Roche J. F. Seymour Honoraria: Abbvie, Acerta, Celgene, Genentech, Janssen, Roche, Sunesis, Takeda Research funding: AbbVie, Genentech, Celgene, Janssen M. Dickinson Honoraria: Roche, AbbVie, GenMab, Novartis, Kite, Gilead, Bristol Myers Squibb Research funding: Roche, Novartis, Gilead, Takeda