PS1255 EFFICACY OF R‐BAC IMMUNOCHEMOTHERAPY IN PATIENTS WITH RELAPSED, REFRACTORY MANTLE CELL LYMPHOMA POST BTK INHIBITOR THERAPY

Background: Effective treatment for relapsed, refractory mantle cell lymphoma (MCL) post Bruton's Tyrosine Kinase inhibitor (BTKi) therapy represents an unmet clinical need with studies consistently reporting dismal outcome. No treatment strategy demonstrates superiority and there is currently no consensus on management. R‐BAC combination therapy (Rituximab, Bendamustine and Cytarabine) has demonstrated excellent upfront response rates in phase 2 trials, but durable responses with R‐CHOP plus maintenance rituximab in older patients and high dose cytarabine regimen in younger patients provides a rationale to reserve R‐BAC for post‐BTKi therapy relapse. Aims: There is currently no data available assessing efficacy of R‐BAC in the post BTKi setting. We first adopted this strategy in 2016 and report our experience to date. Methods: 22 relapsed, refractory MCL patients post BTKi therapy started R‐BAC between December 2016 and December 2018. Treatment consisted of rituximab (375 mg/m 2 or 500 mg) D1, bendamustine 70 mg/m 2 D1 and D2 and cytarabine 500 mg/m 2 D1 to D3 in a 28 day cycle. 16 patients were treated in the UK and 6 patients in Italy. Response to therapy was measured using RECIST criteria. Data was collected retrospectively from hospital records by the treating physician. Results: Median age at time of R‐BAC was 64.8 years (range 43 to 79) and 81.8% of patients were male. At diagnosis MIPI was low risk 25.0%, intermediate risk 20.0% and high risk 55.0%. 22.7% had blastoid morphology and 50.0% commenced second line therapy within 2 years of initial diagnosis. Patients received a median 2 prior lines of systemic therapy (range 1 to 6). Frontline therapy included high dose cytarabine containing regimen (63.6%) plus consolidation AutoSCT (40.9%), R‐CHOP (22.7%), R‐CVP (4.5%) and ibrutinib plus rituximab (9.1%). Prior BTKi therapy included: ibrutinib (n = 18), acalabrutinib (n = 2), tirabrutinib (n = 1) and M7583 (n = 1). ORR to prior BTKi therapy was 54.5% (CR 22.7%) and median time on therapy was 5.8 months (range 1.0 to 39.5). All patients stopped BTKi therapy due to progressive disease (90.9%) or failure to respond (9.1%). All but 1 patient received R‐BAC directly after relapse on BTKi. Patients received a median of 4 cycles of treatment (range 1 to 6). 5 patients received attenuated doses of chemotherapy at clinician's discretion from start of therapy and 7 additional patients received attenuated doses beyond cycle 1 to avoid excess toxicity. ORR to R‐BAC was 90.5% (CR rate 57.1%), median PFS 7.3 months (95% CI 6.2 to 13.1) and estimated median OS 11.2 months (95% CI 8.9 to 15.9). 16 patients completed the planned treatment course, 1 stopped early due to prolonged cytopenias and 4 stopped early due to progressive disease. 5 patients received subsequent consolidation allogeneic SCT. 9 patients remain in remission, including 4 beyond 12 months follow‐up. Toxicity: 9 patients (40.9%) required admission during R‐BAC, including 7 with neutropenic fever (31.8%) and 77.8% patients required transfusion support. There were no treatment related mortalities. Summary/Conclusion: This population, enriched for patients with high risk features, showed excellent response rates to R‐BAC. The treatment had acceptable toxicity, maintained efficacy at attenuated doses and was used successfully as a bridge to allogeneic SCT. R‐BAC appears to represent a good treatment option in post‐BTKi MCL and compares well to other documented treatment options.