P1140: combination anti-pd1 antibody and rituximab followed by r-chop for newly diagnosed dlbcl in elderly patients: analysis of the phase ii trend trial

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with diffuse large B-cell lymphoma (DLBCL) in the elderly face challenges in treatment due to comorbidities and tolerance of chemotherapy. Besides, increased proportion of ABC/non-GCB subgroups, complex molecular features associated with unfavorable prognosis are also present with increased frequency with advancing age. These characteristics foreshadow distinct biological or immune microenvironment features of DLBCL in the elderly. Although clinical benefit of single-agent anti-PD-1 antibody in DLBCL was not obvious, pre-use anti-PD-1 antibody as first-line may be an opportune for elderly DLBCL. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody has been approved by the National Medical Products Administration for the treatment of various cancers. Aims: The primary endpoints were objective response rate (ORR) of rituximab combined with toripalimab and ORR after R-CHOP regimen. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. This trial was registered at ClinicalTrials.gov (NCT04058470). Methods: Patients aged 60-85 years, ECOG 0-2 with untreated DLBCL or grade 3b follicular lymphoma and at least one measurable or evaluable lesion were enrolled. This study consisted of a phase 1b (toripalimab dose escalation) followed by a phase 2 expansion portion. In the phase Ib, a standard “3 + 3” design was utilized to identify the MTD, DLT and recommended phase 2 dosage (RP2D) of toripalimab. In phase 2, patients received 2 cycles of toripalimab (RP2D) plus rituximab (375mg/m2) every 3 weeks. They allowed to accept two additional cycles of toripalimab plus rituximab (To-Ri) if they got complete response (CR) after the first 2 cycles. To-Ri followed by R-CHOP (21) up to 6 cycles then Toripalimab (RP2D) maintenance 6 cycles (q 30 days) after CR or CMR post R-CHOP. ORR based on Lugano 2016 criteria and adverse events (AEs) were defined according to CTCAE 5.0. Results: From December 2020 to February 2023, 48eligible patients were enrolled. Median age 67 years (range, 60-83), 20 (41.6%) male, 21 (43.8%) patients with stage III/IV, 34(70.8%) patients with extranodal disease, 12 (25.0%) patients with IPI score ≥ 3 points, and non-GCB(n=34), double expression (DEL, n=7), EBV+DLBCL(n=6), double/triple hit lymphoma (DHL/THL, n=2). In phase Ib, no MTD or DLT events were observed, RP2D of Toripalimab was 240mg. Of 44 response evaluable patients, 18 patients completed To-Ri×4, 33 (75.0%) achieved response including 22 (50.0%) patients with CR post To-Ri. Key responded to To-Ri including non-GCB (75.0%, n=24), GCB (57.1%, n=8), EBV+DLBCL (66.7%, n=4), DEL (85.7%, n=6), DHL/THL (100%, n=2), primary gastrointestinal tract involved (63.6%, n=7/11) and primary nasal involved (87.5%, 7/8). ORR and CR post R-CHOP were 100% (44/44) and 95.5% (42/44). With a median follow-up of 15.4 months, 1-year PFS and OS were 85.5% and 95.4%. Forty-four (100%) patients reported treatment-related AEs (TRAEs). The most frequently observed (≥10%) TRAEs were abnormal liver function (45.5%), anemia (43.2%), lymphopenia (34.1%), neutropenia (27.3%), hypothyroidism (22.7%), nausea (22.7%). Summary/Conclusion: Toripalimab plus Rituximab as a first-line treatment then followed by R-CHOP yielded high CR rate and manageable toxicities in newly diagnosed elderly DLBCL, especially for patients with extranodal disease and high-grade lymphoma. This treatment strategy deserves further study. Keywords: Phase II, DLBCL