RITUXIMAB MAINTENANCE FOR PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA IN FIRST COMPLETE REMISSION: RESULTS FROM A RANDOMIZED HOVON‐NORDIC LYMPHOMA GROUP PHASE III STUDY

Abstract

non-GCB DLBCL as single agents, and result in synthetic lethality in non-GCB DLBCL models when combined. In relapsed non-GCB DLBCL, rituximab (R), L and I result in overall response rate (ORR) of 55% (Ramchandren, ASH 2018). We conducted an investigator initiated, single-arm, open-label, phase 2 study (NCT02636322) of RLI alone and then with chemotherapy in newly diagnosed non-GCB DLBCL patients, and report the final results of the RLI lead in. Methods: Adult patients with newly diagnosed non-GCB DLBCL, determined by the Hans method, with adequate organ function and performance status were eligible. The primary objectives were to determine (1A) the ORR of two cycles of RLI as initial therapy, and (1B) the complete response rate (CRR) after 6 cycles of chemotherapy combined with RLI. All patients were treated with rituximab 375 mg/m2 IV day 1, ibrutinib 560 mg po daily, and lenalidomide 25 mg po days 1-10 of 21 day cycles for 2 cycles, followed by 6 additional cycles of RLI with chemotherapy (CHOP or EPOCH per treating MD choice). Responses were assessed with PET/CT as per the Lugano criteria. Growth factors, venous thromboembolism prophylaxis, and pneumocystis pneumonia prophylaxis were required for all patients. Results: The protocol accrued 60 patients from May 2016 – February 2019, with 52 patients evaluable for disease response (2 withdrew consent prior to restaging, 6 pending restaging prior to abstract deadline). The median age was 64 years (range: 30-83), 28% were >= 70 years, and 50% were female. Half the patients had poor risk IPI, 61% had advanced stage, and 71% had a Ki-67 of >= 80%. One patient had a fatal fungal infection (CNS aspergillosis) attributed to high dose corticosteroids for symptom control during screening and with RLI, leading to prohibition of corticosteroids during the RLI only cycles with no further fungal infections identified. The ORR for 2 cycles of RLI alone was 84.6% (n = 44), and the CRR was 38.5% (n = 20). One patient refused to proceed with the pre-planned chemotherapy after achieving a CR with 2 cycles of RLI, and remains relapse free with no additional therapy 18 months later. Preliminary results demonstrate a CRR of 100% for the full therapy (RLI for 2 cycles, RLIchemo for 6 cycles), with updates to be presented at the meeting. Conclusions: The Smart Start trial demonstrates the chemotherapyfree combination of rituximab 375 mg/m2, ibrutinib 560 mg, and lenalidomide 25mg is highly effective in patients with newly diagnosed non-GCB DLBCL. Further studies are planned with other novel agents and with fewer cycles of chemotherapy consolidation for patients achieving a CR with RLI alone.