Punnoose, Elizabeth A.

8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B (1.3 mg/m2) and d (20 mg). The primary endpoint was PFS; key secondary endpoints included overall response and overall survival (OS). Results: 291 pts were randomized; 194 to Ven, 97 to Pbo. Pt characteristics were well balanced among arms. In the Ven arm, median age was 66, 17% had high-risk cytogenetics, 11% had t(11;14), and 34% had BCL2high gene expression. As of 13 Sept 2019, 59 pts were still on study, 45 (23%) Ven vs 14 (14%) Pbo. At a median follow-up of 28.6 months, there were 64 (33%) deaths in the Ven arm vs 24 (25%) in Pbo. At the initial data cutoff (26 Nov 2018), PFS HR was 0.63 (0.44,0.90) and OS HR was 2.03 (1.04,3.95). Table shows updated PFS and OS. Most common treatment-emergent adverse events (TEAEs) with Ven were diarrhea (59%), nausea (37%), and constipation (35%). Most common grade 3/4 AEs (Ven/Pbo) were neutropenia (21%/8%), thrombocytopenia (15%/30%), anemia (16%/15%), diarrhea (15%/12%), and pneumonia (18%/13%). Serious AEs occurred in 54% Ven and 52% Pbo pts. 24% discontinued Ven due to AEs vs 12% Pbo. There were 14 treatment-emergent deaths in the Ven arm and 1 in Pbo. Conclusions: The addition of Ven to Bd significantly improves PFS but resulted in increased mortality vs Pbo in the total population. Greatest PFS improvement with Ven was observed in pts with t(11;14) or BCL2high gene expression, where Ven shows a favorable benefit-risk profile. The study continues for final OS analysis. Clinical trial information: NCT02755597 . [Table: see text]

Background: Overexpression of the anti-apoptotic BCL-2 protein promotes multiple myeloma (MM) cell survival. Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis and has shown synergistic activity with bortezomib (B) and dexamethasone (d). Phase 1 studies in relapsed/refractory (RR) MM demonstrated encouraging clinical efficacy of Ven + d in t(11;14) MM and in a broader patient (pt) population in combination with Bd. Recent results from the Phase 3 BELLINI study of Ven vs placebo (Pbo) + Bd in pts with RRMM demonstrated that pts treated with Ven + Bd had improved clinical response rates and progression-free survival (PFS) vs Pbo, although the overall survival (OS) result was in favor of Pbo. Subgroup analyses showed different efficacy and survival outcomes based on tumor cytogenetics and BCL-2 expression. Results of pre-specified subgroup analyses and additional retrospective correlative biomarker analyses in the Phase 3 BELLINI study are described herein. Methods: BELLINI (NCT02755597) was a randomized, double-blind, multicenter Phase 3 study of Ven or Pbo + Bd in pts with RRMM who received 1-3 prior therapies and were either sensitive or naïve to PIs. Pts were randomized 2:1 to receive Ven 800 mg/day or Pbo + Bd. The following biomarker analyses were performed by central laboratory assessments of pre-treatment tumor samples: BCL-2 protein expression by immunohistochemistry (IHC) analysis of bone marrow (BM) core biopsies; BCL2 gene expression by quantitative PCR (qPCR) and cytogenetic abnormalities by interphase fluorescence in situ hybridization (FISH) analysis of CD138-enriched BM mononuclear cells. Correlation between BCL-2 (protein and gene) expression, cytogenetics, and outcomes were examined by Kruskal-Wallis tests and by hazard ratio (HR) using the Cox proportional hazard model. Results: As of the data cut-off of 18 Mar 2019, 291 pts were randomized, 194 to the Ven arm and 97 to the Pbo arm. Out of the 291 pts randomized, 177 pts (61%) were evaluable by IHC, 257 pts (88%) by qPCR, and 262 pts (90%) by FISH. A broad range of BCL2 gene expression was observed (median 2-DCt: 0.212 [range: 0-5.21]), which strongly correlated with protein expression (median 2-DCt 0.115 in BCL-2 IHC Low vs 0.277 in BCL-2 IHC High, p=0.0021). t(11;14) MM had the highest levels of BCL-2 expression (23/23 BCL-2 High by IHC; median 2-DCt 0.406 vs 0.212 in t(11;14) negative, p=0.0132), however high BCL-2 expression was not limited to the t(11;14) subgroup. Univariate analyses showed higher BCL2 expression in pt tumor samples with del(13q) (median 2-DCt 0.333 vs 0.159 in pts without del(13q), p=0.0008) and gain(1q) (median 2-DCt 0. 295 vs 0.180 in pts without gain(1q), p=0.0059). Bootstrapping and aggregating thresholds from trees (BATTing) was used retrospectively to identify an estimated threshold value for BCL2 expression (2-DCt ≥0.323) that could provide optimum selection of pts with maximum improvement in PFS when treated with Ven+Bd. Biomarker subgroups with the greatest PFS improvement were t(11;14) (HR=0.10; 95% CI: 0.02-0.46, p=0.003) and High BCL2 by qPCR (HR=0.26; 95% CI: 0.13-0.51, p<0.001; Table 1). Since the t(11;14) and High BCL2 patient populations do not completely overlap (20% of High BCL2 pts were t(11;14) and 54% of t(11;14) were High BCL2), a combined subgroup analysis was performed. For pts with t(11;14) or High BCL2, the median PFS was not reached in the Ven arm vs 9.9 mo in Pbo (HR=0.26, 95% CI: 0.14-0.48, p<0.001; Table 1). Higher overall response (ORR, 88% vs 70%), very good partial response or better (≥VGPR, 73% vs 33%), and complete response or better (≥CR, 42% vs 3%) rates were observed in the Ven vs Pbo arm (Table 2). Minimal residual disease negativity (MRD-, 10-5) rate was also higher for t(11;14) or High BCL2 pts in the Ven vs Pbo arm (19% vs 0%). Median overall survival (OS) was not reached in either arm but was similar between treatment arms for the combined group with t(11;14) or High BCL2 pts (HR=0.92, 95% CI=0.39-2.16, p=0.85). In contrast, in the t(11;14) negative and Low BCL2 pts, OS favored Pbo (HR=3.13, 95% CI=1.2-8.13, p=0.019; Table 1). Conclusions: Adding Ven to Bd demonstrates significant efficacy in pts with RRMM harboring either t(11;14) or tumor cells expressing high levels of BCL2. The benefit-risk profile appears to be favorable in these subsets of pts and additional studies to gain further safety and efficacy information are warranted. Disclosures Harrison: GSK: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: investigator on studies, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cavo:celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. De La Rubia:AMGEN: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; Janssen: Consultancy; Celgene Corporation: Consultancy. Popat:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses; Janssen: Honoraria, Other: travel support to meetings; GSK: Consultancy, Honoraria; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Other: travel, accommodations, expenses. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Hungria:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Salwender:Amgen: Honoraria, Other: Travel or accommodations; Bristol-Myers Squibb: Honoraria, Other: Travel or accommodations; Janssen Cilag: Honoraria, Other: Travel or accommodations; Sanofi: Honoraria, Other: Travel or accommodations; Celgene: Honoraria, Other: Travel or accommodations; AbbVie: Honoraria; Takeda: Honoraria, Other: Travel or accommodations. Suzuki:Ono: Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Spencer:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Specialised Therapeutics Australia: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. O'Dwyer:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy; GlycoMimetics Inc: Research Funding; BMS: Research Funding; Onkimmune: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Garg:Janssen: Honoraria; Novartis, Janssen: Research Funding; Janssen, Takeda, Novartis: Other: Travel expenses. Punnoose:Roche: Other: Stock/stock options; Genentech, Inc.: Employment. Jalaluddin:AbbVie: Employment, Other: Stock/stock options. Jia:AbbVie: Employment, Other: Stock/stock options. Yang:AbbVie: Employment, Other: Stock/stock options. Sun:AbbVie: Employment, Other: Stock/stock options. Ward:AbbVie: Employment, Other: Stock/stock options. Maciag:AbbVie: Employment, Other: Stock/stock options. Ross:AbbVie: Employment, Other: Stock/stock options. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. OffLabel Disclosure: Venetoclax is a BCL-2 inhibitor that is FDA-approved in some indications. This presentation will focus on venetoclax for treatment of multiple myeloma, which is not an approved indication.

Background: Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis in multiple myeloma (MM) cells and has shown synergistic activity with the proteasome inhibitor (PI) bortezomib (B) and dexamethasone (d). Ven ± d had encouraging clinical efficacy in both t(11;14) MM and in pts irrespective of genetic background when administered with B, with a tolerable safety profile in Phase 1 studies. Here, we provide updated efficacy and safety of Ven vs placebo (Pbo) + Bd in pts with relapsed/refractory (RR) MM, including subgroup analyses, in the BELLINI study. Methods: BELLINI (NCT02755597) was a Phase 3, randomized, double-blind, multicenter study of Ven or Pbo + Bd in pts with RRMM who received 1 - 3 prior therapies and were either sensitive or naïve to PIs. Pts were randomized 2:1 to receive Ven 800 mg/day or Pbo + Bd. Cycles 1-8 were 21-day with B 1.3 mg/m2 on Days 1, 4, 8, 11 + d 20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12. Cycles 9+ were 35-day with B 1.3 mg/m2 on Days 1, 8, 15, 22 + d 20 mg Day 1, 2, 8, 9, 15, 16, 22, 23. The primary endpoint was progression-free survival (PFS) by independent review committee (IRC). Results: A total of 291 pts were randomized, 194 to the Ven arm and 97 to the Pbo arm. Median age was 66 (range, 36 - 87); 53% had ISS II/III disease; 54% received 2 or 3 prior lines of therapy; 59% had prior stem cell transplant; 70% had prior PI, 68% had prior immunomodulatory drug, 41% had both. Among pts with evaluable results, 18% had high-risk cytogenetics, 13% had MM positive for t(11;14), and 79% had high levels of BCL-2 protein by immunohistochemistry (IHC). In the primary endpoint analysis per IRC, the median PFS was 22.4 months (m) in Ven vs 11.5 m in Pbo (HR=0.630, p=0.01), with a median follow-up of 18.7 m (as of 26 Nov 2018). As of updated analysis based on a data cut-off of 18 March 2019, the median PFS (per investigator [INV]) was 22.9 m in Ven vs 11.4 m in Pbo (HR=0.587, p=0.001; Table 1), with a median follow-up of 22.7 m. Per INV, higher overall response (ORR, 84% vs 70%, p=0.009) and very good partial or better response (≥VGPR, 61% vs 40%, p<0.001; Table 2) rates were observed in Ven vs Pbo. Minimal residual disease negativity rate (by next-generation sequencing) was also higher in the Ven arm vs Pbo (MRD- [10-5], 13% vs 1%). Median duration of response was 23.4 m for Ven and 12.8 m for Pbo. In the overall population, median overall survival (OS) was not reached in either arm but continued to favor Pbo (HR 1.474, 95% CI=0.870-2.498). A total of 70 deaths have been reported, 51 (26%) in the Ven arm and 19 (20%) in the Pbo arm. In the safety population (N=289), the most common treatment-emergent adverse events (TEAEs; Ven/Pbo) were diarrhea (59%/48%), nausea (37%/22%), constipation (35%/31%), and fatigue (31%/32%). The most common Grade 3/4 TEAEs were neutropenia (18%/8%), pneumonia (17%/12%), anemia (16%/15%), thrombocytopenia (15%/30%), and diarrhea (15%/12%); 23%/12% discontinued Ven due to a TEAE. The rates of serious AEs (51%/51%) and serious infections (30%/28%) were comparable between arms. There were 69 deaths in the safety population: in the Ven arm, 14 were treatment-emergent (TE; treatment start to 30 days after discontinuation) and 36 were non-TE (>30 days after treatment discontinuation); in the Pbo arm, 1 was TE and 18 were non-TE. In the t(11;14) subgroup, median PFS has not been reached for pts receiving Ven, but was 9.3 m for Pbo (HR=0.095; per INV). In the t(11;14)-negative (neg) subgroup, median PFS was 22.4 m and 10.7 m for Ven and Pbo, respectively (HR=0.627; per INV). Median OS has not been reached in either arm for the t(11;14) and t(11;14)-neg subgroups, although the HR favored Ven in t(11;14) pts, and Pbo in t(11;14)-neg pts. Analyses indicate that low BCL-2 expression by IHC and high-risk cytogenetics (defined as t(4;14, t(14;16), or del(17p)) were associated with decreased PFS and OS in the Ven arm (Table 1). In the high-risk cytogenetics pts, median PFS was 11.4 m in both arms (HR=0.99), and median OS has not been reached in either arm but favors Pbo (HR=10.6). In the subgroup with low BCL-2 expression by IHC, median PFS was 11.7 m and 17.0 m for Ven and Pbo, respectively (HR=1.42), and median OS was 21.3 m in the Ven arm and not reached in Pbo (HR=4.58). Conclusions: Updated analysis of BELLINI continue to reflect a favorable benefit-risk profile in t(11;14) pts, with meaningful clinical responses and improvement in PFS, as well as a positive trend in OS in this subgroup when treated with Ven + Bd. Disclosures Moreau: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Harrison:Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: investigator on studies, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cavo:sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria. De La Rubia:Janssen: Consultancy; Takeda: Consultancy; Celgene Corporation: Consultancy; AMGEN: Consultancy; AbbVie: Consultancy. Popat:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses; Janssen: Honoraria, Other: travel support to meetings; Takeda: Honoraria, Other: travel, accommodations, expenses; GSK: Consultancy, Honoraria; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Hungria:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Salwender:Amgen: Honoraria, Other: Travel or accommodations; Takeda: Honoraria, Other: Travel or accommodations; Bristol-Myers Squibb: Honoraria, Other: Travel or accommodations; Sanofi: Honoraria, Other: Travel or accommodations; Celgene: Honoraria, Other: Travel or accommodations; AbbVie: Honoraria; Janssen Cilag: Honoraria, Other: Travel or accommodations. Suzuki:Ono: Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Gay:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Mikala:Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; AbbVie: Honoraria, Research Funding. Punnoose:Genentech, Inc.: Employment; Roche: Other: Stock/stock options. Hong:Genentech Inc.: Employment, Equity Ownership; Roche: Equity Ownership. Sood:AbbVie: Employment, Other: Stock/stock options. Jalaluddin:AbbVie: Employment, Other: Stock/stock options. Ross:AbbVie: Employment, Other: Stock/stock options. Ward:AbbVie: Employment, Other: Stock/stock options. Maciag:AbbVie: Employment, Other: Stock/stock options. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. OffLabel Disclosure: Venetoclax is a BCL-2 inhibitor that is FDA-approved in some indications. This presentation will focus on venetoclax for treatment of multiple myeloma, which is not an approved indication.

Key Points Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile in patients with relapsed/refractory MM. Venetoclax monotherapy has demonstrated antimyeloma activity in patients with relapsed/refractory MM positive for t(11;14).

Key Points In relapsed/refractory MM, venetoclax plus bortezomib and dexamethasone appears to be safe and efficacious. This is a novel therapeutic approach for MM.