No abstract

Our results suggest that lymphomas overexpress LDL receptors that make room for using LDE as drug-targeting vehicle and that the LDE-etoposide preparation is suitable for patient use.

Introduction: Daratumumab (DARA), a human, IgGκ monoclonal antibody targeting CD38, is approved either as a single agent or in combination with anti-myeloma regimens for newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). In phase 3 studies, DARA-based regimens reduced the disease progression or death risk by ≥44%, nearly doubled the rates of complete response (CR) or better, and tripled minimal residual disease (MRD)-negativity rates (10-5 sensitivity threshold) in NDMM or RRMM pts (Palumbo A, et al. N Engl J Med 2016. 375[8]:754-766; Dimopoulos MA, et al. N Engl J Med 2016. 375[14]:1319-1331; Mateos MV, et al. N Engl J Med 2018. 378[6]:518-528; Facon T, et al. N Engl J Med 2019. 380[22]2104-2015). In the phase 3 CASTOR study (median follow-up 40.0 mo), D-Vd reduced the risk of disease progression or death by 69% and induced higher rates of deeper responses vs Vd in RRMM pts. Pts who received 1 prior line (PL) of therapy achieved the greatest benefit with D-Vd. Here, we examine updated (47.0 mo median follow-up) efficacy and safety of D-Vd vs Vd in CASTOR, with a focus on pts with 1 PL of therapy. Methods: In CASTOR, pts were randomized to 8 cycles (21 d/cycle) of V (1.3 mg/m2, SC) on Days 1, 4, 8, and 11 and dexamethasone (20 mg, PO or IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 ± DARA (16 mg/kg, IV) given weekly for Cycles 1-3, Q3W for Cycles 4-8, and Q4W thereafter. Cytogenetic risk was evaluated by local fluorescence in situ hybridization or karyotyping; high risk was defined as the presence of t(4;14), t(14;16), or del17p abnormalities. Results: A total of 498 pts were randomized (D-Vd, n = 251; Vd, n = 247) and included in the intent-to-treat (ITT) population. A total of 235 pts had 1 PL of therapy (D-Vd, n = 122; Vd, n = 113). After a median follow-up of 47.0 mo, progression-free survival (PFS) was significantly prolonged with D-Vd vs Vd in the ITT population (median: 16.7 vs 7.1 mo; HR, 0.31; 95% CI, 0.25-0.39, P <0.0001). The PFS benefit for D-Vd vs Vd was maintained in pts with prior V (median: 12.1 vs 6.7 mo; HR, 0.34; 95% CI, 0.26-0.46, P <0.0001), with prior R (median: 9.5 vs 6.1 mo; HR, 0.40; 95% CI, 0.28-0.58, P <0.0001), and high (median: 12.6 vs 6.2 mo; HR, 0.41; 95% CI, 0.21-0.83, P = 0.0106) and standard cytogenetic risk (median: 16.6 vs 6.6 mo; HR, 0.26; 95% CI, 0.18-0.36, P <0.0001). D-Vd significantly prolonged PFS on the subsequent line of therapy (PFS2) vs Vd (median: 34.6 vs 20.7 mo; HR, 0.47, 95% CI, 0.37-0.59; P <0.0001; Figure 1A). At the time of analysis, 114 deaths with D-Vd and 132 deaths with Vd were observed with 3-yr overall survival (OS) rates of 61% vs 51%, respectively; follow-up for OS is ongoing. The overall response rate (ORR; 85% vs 63%), ≥very good partial response (VGPR) rate (63% vs 29%) and ≥CR rate (30% vs 10%) were all significantly higher (all P <0.0001) with D-Vd vs Vd. Among 1 PL pts, median PFS was 27.0 vs 7.9 mo (HR, 0.21; 95% CI, 0.15-0.31, P <0.0001) for D-Vd vs Vd. The PFS benefit for D-Vd vs Vd was maintained among 1 PL pts previously exposed to V (median: 20.4 vs 8.0 mo; HR, 0.22; 95% CI, 0.13-0.37; P <0.0001) or R (median: 21.2 vs 7.0 mo; HR, 0.30; 95% CI, 0.11-0.82; P = 0.0140). PFS2 was also significantly prolonged with D-Vd vs Vd in 1 PL pts (median: not reached vs 23.4 mo; HR, 0.34, 95% CI, 0.24-0.49; P <0.0001; Figure 1B); 42-mo PFS2 rates were 58% vs 19%, respectively. For 1 PL pts, 39 vs 56 deaths were observed with D-Vd vs Vd, with 3-yr OS rates of 76% vs 57%, respectively. ORR (92% vs 74%; P = 0.0007) and rates of ≥VGPR (77% vs 42%; P <0.0001) and ≥CR (43% vs 15%; P <0.0001) were all significantly higher with D-Vd vs Vd. Additional data including MRD analyses will be presented. The most common (≥5%) grade 3/4 treatment-emergent adverse events (TEAEs) with D-Vd vs Vd included thrombocytopenia (46% vs 33%), anemia (16% vs 16%), neutropenia (14% vs 5%), pneumonia (10% vs 10%), lymphopenia (10% vs 3%), hypertension (7% vs 1%), and peripheral sensory neuropathy (5% vs 7%). Discontinuation rates due to TEAEs were similar for D-Vd vs Vd (10% vs 9%). The rate of invasive second primary malignancy rates were 4.9% in the D-Vd group vs 1.7% in the Vd group. Conclusions : In this updated analysis of CASTOR, D-Vd maintains significant PFS and ORR benefits in RRMM, with the greatest benefit achieved by pts who received 1 PL of therapy. The safety profile of D-Vd remains consistent with longer follow-up, with no new safety concerns reported. These data continue to suggest that administration of D-Vd to RRMM pts after first relapse may provide the greatest clinical benefit. Disclosures Weisel: Juno: Consultancy; Adaptive Biotech: Consultancy, Honoraria; GSK: Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Sonneveld:SkylineDx: Research Funding; Takeda: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; BMS: Honoraria. Mateos:Adaptive: Honoraria; 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; EDO: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees. Hungria:BMS: Consultancy, Honoraria, Speakers Bureau; Janssen: 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; 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; Takeda: 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; 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. Spencer:Sanofi: Consultancy, Honoraria, 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, Research Funding, Speakers Bureau; Amgen: 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; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Specialised Therapeutics Australia: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Oncology: 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. Estell:Janssen/ Celgene: Membership on an entity's Board of Directors or advisory committees. Barreto:Hemocentro, USP-Ribeira; Preto-SP: Employment. Corradini:Gilead: Honoraria, Other: Travel Costs; AbbVie: Consultancy, Honoraria, Other: Travel Costs; Amgen: Honoraria; Celgene: Honoraria, Other: Travel Costs; Daiichi Sankyo: Honoraria; BMS: Other: Travel Costs; Takeda: Honoraria, Other: Travel Costs; Servier: Honoraria; Kite: Honoraria; Novartis: Honoraria, Other: Travel Costs; Roche: Honoraria; Sanofi: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria, Other: Travel Costs; Jazz Pharmaceutics: Honoraria. Krevvata:Janssen: Employment. Trivedi:Janssen: Employment, Equity Ownership. Qin:Janssen: Employment, Equity Ownership. Pei:Janssen: Employment, Equity Ownership. Ukropec:Janssen: Employment, Equity Ownership. Kobos:Janssen: Employment. Qi:Janssen: Employment. Nooka:Amgen: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation; GSK: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation.

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n 5 52) or dexamethasone with thalidomide (arm B; n 5 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 22-38) and 64% in arm B (95% CI 57-71; P 5 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P 5 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P 5 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. 87:948-952, 2012. V

Relatively little is known about the outcomes of multiple myeloma in Latin America, a world region where incorporation of novel agents is generally slow. In the current retrospective-prospective study, we aimed to describe the patterns of care and treatment results in five Latin American countries. Between April 2007 and October 2009, patients who had been diagnosed from January 2005 to December 2007 were registered at 23 institutions from Argentina, Brazil, Chile, Mexico, and Peru. We divided patients into two cohorts, according to transplantation eligibility, and analyzed them with regard to first-line treatment and overall survival (OS). We analyzed a total of 852 patients, 46.9 % of whom were female. The median follow-up was 62 months. Among transplantation-ineligible patients (N = 461), the mean age was 67.4 years, approximately one third of patients received a thalidomide-based treatment in the first line, and the median OS was 43.0 months. Transplantation-eligible patients (N = 391) had a mean age of 54.7 years and a median OS of 73.6 months. Autologous transplantation was performed in 58.6 % of the patients for whom this procedure was initially planned and in only 26.9 % of the overall patients. Our long-term results reflect the contemporary literature for patients with multiple myeloma treated with autologous transplantation and thalidomide-based regimens in clinical trials and observational studies. However, further efforts are needed to approve and incorporate novel agents in Latin American countries, as well as to increase access to transplantation, in order to achieve the expected improvements in patient outcomes.

No abstract

These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

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&lt;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&lt;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.