PF296 UPDATE OF THE SINGLE‐ARM PHASE II L‐MIND STUDY OF MOR208 PLUS LENALIDOMIDE IN RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA: HIGH OVERALL RESPONSE RATES IN PATIENT SUBGROUPS WITH POOR PROGNOSIS

Abstract

Please indicate where the abstract has been published before: 2018 ASH abstract was published in Blood 2018 132:227; doi: https://doi.org/10.1182/blood‐2018–99–113399Background:The CD19 antigen is broadly and homogeneously expressed across different B‐cell malignancies, including relapsed/refractory diffuse large B‐cell lymphoma (R‐R DLBCL). MOR208, an Fc‐enhanced, humanized, anti‐CD19 monoclonal antibody has shown single agent activity in patients (pts) with R‐R DLBCL and encouraging activity when combined with lenalidomide (LEN) in the single‐arm phase II L‐MIND study. Here we report updated data for the primary endpoint and patient subgroup analyses (data cutoff of June 5, 2018).Aims:To assess the efficacy and safety of MOR208 combined with LEN in pts with R‐R DLBCL.Methods:Key inclusion criteria were adequate organ function, ≤3 prior lines of therapy, including ≥1 anti‐CD20 therapy, and ineligibility for stem cell transplantation. Treatment comprised up to 12, 28‐day (d) cycles (C) of MOR208, 12 mg/kg IV, weekly C1–3 (loading dose on d4 of C1), and every two weeks C4–12 plus LEN 25 mg PO d1–21, C1–12. Pts progression‐free after 12 C received MOR208 every two weeks until progression. The primary endpoint was independent review committee (IRC)‐assessed overall response rate (ORR) as per Cheson 2007 criteria. Secondary endpoints included investigator (INV)‐assessed ORR, duration of response, progression‐free survival (PFS) and overall survival (OS), safety, and analysis of outcomes according to cell of origin.Results:Recruitment is complete with 81 pts enrolled and analyzed for safety and efficacy. Median age was 72 years (range 41–87), 41 (51%) pts had received ≥2 prior lines of therapy (median 2, range 1–4), 19 (23%) pts had early relapse (≤12 months from initial diagnosis), 32 (40%) pts were rituximab refractory (no response to or progression during or within 6 months of a prior rituximab therapy), 34 (42%) pts were refractory to their last therapy, 21 (26%) pts had non‐germinal center B cell‐like (GCB)‐DLBCL and 40 (49%) had GCB‐DLBCL, and 42 (52%) pts had an International Prognostic Index (IPI) of 3–5. MOR208 plus LEN therapy was well tolerated, and 58 (72%) of pts stayed on a LEN dose of ≥20 mg/day. Treatment‐related serious adverse events consisted of infections (10%) and neutropenic fever (5%). No infusion‐related reactions were reported. Investigator (INV)‐assessed complete response (CR) and partial response rates were 33% and 25%, respectively, giving an ORR of 58%. IRC‐assessed ORR and CR rates were 54% and 32%, respectively. INV‐assessed ORR was 70% in pts with 1 prior therapy, 46% in pts with ≥2 prior therapies, 59% in rituximab‐refractory pts, 56% in last treatment‐refractory pts, 58% in early relapse pts, 57% in pts with a baseline IPI of 3–5, and 71% in pts with non‐GCB‐DLBCL and 53% in pts with GCB‐DLBCL, respectively. At a median follow‐up of 12 months, the INV‐assessed median PFS and OS (intention‐to‐treat analysis) were 16.2 months (95% CI: 6.3 months–NR) and not reached (95% CI: 18.6 months–NR), respectively.Summary/Conclusion:The combination of MOR208 and LEN has shown encouraging activity including a durable PFS in elderly pts with R‐R DLBCL. High activity and long lasting responses were also reported in patient subgroups with poor prognosis, who urgently need effective therapies.