Combination of acalabrutinib with rituximab and lenalidomide in relapsed/refractory B cell non‐Hodgkin lymphoma

Introduction: Previous studies have shown that combination of acalabrutinib with rituximab and lenalidomide has a synergistic effect in killing NHL cells. We hypothesized that the R2A regimen would show satisfying efficacy for relapsed/refractory B cell NHL and a tolerable toxicity profile. Methods: In this single-arm, phase 2, multicenter study in Republic of Korea, 66 patients (median age 67.5, range 20–87) with relapsed/refractory B cell NHL were included. Patients who were diagnosed with mantle cell lymphoma were excluded. The patients received the R2A regimen, a cycle of which consisted of 28 days with acalabrutinib 100 mg twice daily from day 1 to day 28, rituximab 375 mg/m2 on day 1, and lenalidomide 20 mg once daily from day 1 to day 21. The patients received R2A up to 6 cycles, and those who responded and remained in response to R2A received maintenance acalabrutinib 100 mg twice daily up to 1 year. The primary outcome of the study was objective response rate (ORR) by Lugano criteria. The secondary outcome of the study includes complete remission (CR) rate, duration of response (DoR), progression free survival (PFS), and biomarker analysis from next generation sequencing. (ClinicalTrials.gov identifier: NCT04094142) Results: Among the 66 patients, 47 patients (71.2%) had non-germinal center B cell like (non-GCB) subtype diffuse large B cell lymphoma (DLBCL) and 11 patients (16.7%) had GCB subtype DLBCL. All patients had received at least one previous line of treatment and 34 patients (51.5%) had 2 or more previous lines of treatment. The ORR was 54.5% [36 patients, 95% confidence interval (CI) 42.4–66.4] and CR rate was 33.3% (22 patients, 95% CI: 22.4–45.4). ORR in the non-GCB subtype DLBCL was 61.7% (95% CI: 46.8–74.8), which tended to be higher than the GCB subtype DLBCL which was 36.4% (95% CI: 13.5–66.8, p = 0.18). The median DoR was 12.9 months for all responders (95% CI: 4.3—not available) and 24.4 months for CR patients (95% CI: 13.8—not available). Total of 13 patients have not experienced progressive disease at the time of data cutoff (Figure 1). At median follow-up duration of 9.1 months, median PFS was 4.4 months (95% CI: 3.5–11.6). A total of 7 patients were found to have MYD88 mutation. Among these patients, total of six patients with MYD88 mutation showed objective response to the R2A regimen with three CR patients. A total of 39 patients (59.1%) experienced adverse events (AE) of any grade. The most common AEs were neutropenia (31.8%), skin rash (25.8%), thrombocytopenia (9.1%) and pruritus (9.1%). One patient was off study due to a drug reaction with eosinophilia and systemic symptom syndrome. The research was funded by: This research was supported in part by Samyang Holdings (provision of lenalidomide), Celltrion Healthcare Co., Ltd. (provision of rituximab biosimilar), and an externally sponsored research program (ESR-18-13701) by AstraZeneca (provision of Acalabrutinib). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies, Molecular Targeted Therapies No conflicts of interests pertinent to the abstract.