2018 ASCO Annual Meeting!
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Type: Oral Abstract Session
Time: Friday June 1, 2:45 PM to 5:45 PM
Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma.
Hematologic Malignancies—Plasma Cell Dyscrasia
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 8004)
Author(s): Luciano J. Costa, Edward Allen Stadtmauer, Gareth John Morgan, Gregory P. Monohan, Tibor Kovacsovics, Nicholas Burwick, Andrzej J. Jakubowiak, Mehrdad Mobasher, Kevin Freise, Jeremy A. Ross, John Carl Pesko, Wijith Munasinghe, Jaclyn Cordero, Lura Morris, Paulo Cesar Maciag, Orlando Bueno, Shaji Kumar; University of Alabama at Birmingham, Troy, AL; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; University of Arkansas for Medical Science, London, AR; University of Kentucky Markey Cancer Center, Lexington, KY; Huntsman Cancer Institute, Salt Lake City, UT; VA Puget Sound Health Care System, University of Washington, Seattle, WA; University of Chicago Medical Center, Chicago, IL; Genentech, Inc., South San Francisco, CA; AbbVie Inc., North Chicago, IL; Mayo Clinic, Rochester, MN
Background: The BCL-2 inhibitor venetoclax (VEN) has demonstrated efficacy, as monotherapy and combined with PI bortezomib, in relapsed/refractory (R/R) multiple myeloma (MM). We report preliminary data for VEN combined with second generation PI carfilzomib and dexamethasone (VENKd) in R/R MM. Methods: In this ongoing phase 2, dose escalation study (NCT02899052), pts with R/R MM received VENKd on 28-d cycles: VEN 400 mg/day + K 27 mg/m2 d1,2,8,9,15,16+ dex 40 mg d1,8,15,22 (Cohort 1), same regimen but with VEN 800 mg/day (Cohort 2), VEN 800 mg/day + K 70 mg/m2 d1,8,15 + dex 40 mg d1,8,15, 22 (Cohort 3/expansion cohort), or VEN 800 mg + K 56 mg/m2 d1,2,8,9,15,16 + dex 40 mg d1,2,8,9,15,16,22,23 (optional Cohort 4; no data available at cutoff). Treatment continued until progressive disease (PD) or unacceptable toxicity. Results: As of 01Dec2017, 26 pts were enrolled. Median age was 67.5 years (40 – 79), 68% had ISS II/III disease, and 23% had t(11;14). Pts received a median of 1 prior therapy (1 – 3); no pts had prior K exposure, 96% had received prior PI (54% refractory), 62% were IMiD refractory, and 35% double refractory. At data cut off, 23 pts were on therapy for 0.3 – 10 months and 3 pts discontinued the study for PD, physician decision, and death. 85% of pts had an AE, grade 3/4 AEs were neutropenia (15%), hypertension (12%), thrombocytopenia (8%), decreased white blood cells (8%), and nausea (4%). 7 serious AEs occurred, but no dose-limiting toxicities were reported. Maximum tolerated dose was not reached and Cohort 3 is being expanded. VEN pharmacokinetics with Kd were comparable to VEN plus bortezomib and dexamethasone. Of 17 pts evaluated after completing ≥2 cycles, 3 had complete response (CR), 2 very good partial response (VGPR), 3 partial response (PR), 3 stable disease, and 2 PD (awaiting response data for 4 pts). Median time to first response was 1 month. Of 5 evaluable pts with t(11;14) MM, 1 achieved CR, 1 VGPR, 3 PR. Conclusions: VENkd is well tolerated with promising preliminary efficacy that supports study in pts with R/R MM. Accrual continues with 34 pts enrolled to date. Updated safety and efficacy results will be available for presentation. Clinical trial information: NCT02899052
2. Pomalidomide (POM), bortezomib, and low‐dose dexamethasone (PVd) vs bortezomib and low-dose dexamethasone (Vd) in lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma (RRMM): Phase 3 OPTIMISMM trial.