Domper, Neus

7520 Background: We report results of a phase 2, open-label study of durvalumab (durva) in combination with R-CHOP or R2-CHOP (R-CHOP + lenalidomide) in previously untreated, high-risk diffuse large B-cell lymphoma (DLBCL). Methods: Subjects (≥18 y; ECOG 0–2) with previously untreated, high/high-intermediate risk DLBCL (IPI ≥3/NCCN-IPI ≥4) were stratified to durva + R-CHOP (Arm A, GCB DLBCL) or R2-CHOP for 6–8 cycles (Arm B, ABC DLBCL) based on cell of origin identified by gene expression followed by durva consolidation up to month 12 from start of induction. After FDA placed clinical holds on trials including combination therapy with checkpoint inhibitors and immunomodulatory agents, the study was revised to include both ABC and GCB in Arm A (durva + R-CHOP). The primary endpoint was complete response rate (CRR) at end of induction; secondary endpoints were rate of subjects continuing to consolidation, safety, and response in biological. Results: A total of 46 subjects were treated (safety; A/B, n=43/3); median age, 62/66 y; male, 61%/67%; ECOG 2, 19%/33%; Ann Arbor stage IV, 79%/33%; bulky disease: 49%/67%; double/triple-hit lymphoma, 30%/33%. As of Aug 2, 2018, 30/3 (A/B) had completed induction therapy, and 19 subjects (A) were ongoing. CRR (95% confidence interval) at end of induction was (A) 54% (37%-71%) and (B) 67% (9%-99%); 68%/67% (A/B) continued to consolidation therapy and were progression free at month 12. Safety profile was as expected for the components of the combination regimen with no new safety signal identified. Frequent treatment-emergent adverse events (TEAEs; ≥25%; A+B) included fatigue (61%), neutropenia (52%), peripheral sensory neuropathy (50%), nausea (46%), diarrhea (28%); constipation, decreased appetite, insomnia, pyrexia (24% each); and alopecia, dizziness, dyspnea, headache, stomatitis (22% each). Grade 3/4 TEAEs occurred in 84%/100% of subjects (A/B), and 3 subjects (2/1) died with no death related to study treatment. Follow-up for efficacy and safety is ongoing. Conclusions: Durva + R-CHOP combination therapy is safe and demonstrates encouraging response rates in subjects with high-risk DLBCL including double-hit lymphoma. Clinical trial information: NCT03003520.