Real-World Data on Safety and Efficacy of Venetoclax-Based Regimens in Relapsed/Refractory t[11;14] Multiple Myeloma

Background: Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein Bcl-2. In Multiple Myeloma [MM] characterized by t[11;14], it is particularly effective with a single-agent response rate of 40%. However, there have been recent safety concerns due to a higher mortality in the venetoclax-arm of BELLINI trial [Kumar et al. EHA 2019]. At our institution, venetoclax has been used off-label for patients with relapsed/refractory t[11;14] MM and AL amyloidosis. Our objective was to present the efficacy and safety data on venetoclax-based regimens at our institution. Methods: The Cleveland Clinic MM database was queried to identify patients meeting the following inclusion criteria: [a] Relapsed or refractory MM [b] Treated with ≥1 cycle of venetoclax-based regimen outside of a clinical trial. All patients meeting the above criteria through April 2019 were included and followed until June 30, 2019. Clinical data were independently reviewed by two investigators, D.B. and R.C., and conflicts were resolved by consensus. The primary endpoint was overall response rate [ORR], per International Myeloma Working Group criteria. Results: A total of ten patients were included in our analysis. Among them, five were males, all were Caucasian, and five had an ECOG performance status of 2 or 3 at treatment initiation. Four patients had ISS stage III at diagnosis. All had t[11;14] translocation, five had deletion [13q], three had deletion [17p], and three had abnormal metaphase cytogenetics with complex karyotype. Patients received a median of 6 lines of treatment prior to venetoclax [range, 2-19]. Notably, 10/10 were refractory to bortezomib, 4 to carfilzomib, 4 to ixazomib, 9 to lenalidomide, 7 to pomalidomide, 3 to elotuzumab, and 8 to daratumumab. Five patients had received prior autologous stem cell transplantation, among whom, two had relapsed within one year post-transplant. A total of five patients had clinical relapse without extramedullary disease, three had clinical relapse with extramedullary disease, and two had biochemical-only relapse at initiation of venetoclax. The most common regimen used was venetoclax in combination with bortezomib and dexamethasone. Venetoclax was initiated at 400 mg for one week and then titrated to 800 mg depending on tolerability and insurance approval. Among nine patients who were evaluable for response, the ORR was 78% [7 out of 9 patients]. Among these seven responding patients, one achieved a complete response, on