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Background: Although daunorubicin/cytarabine ("3+7")-based chemotherapy produces complete remission (CR) rates of 70% in younger adults, a significant proportion require re-induction to achieve CR or are refractory. Among those achieving CR, relapse after post-remission therapy is common and limits cure. Venetoclax (VEN) is an oral, selective BCL-2 inhibitor that promotes mitochondrial-mediated apoptosis in myeloblasts during cytotoxic stress. VEN plus hypomethylating agents in untreated unfit elderly AML patients (pts) elicits high response rates and improves overall survival. We hypothesize that VEN in combination with "3+7" could lead to a higher rate of measurable residual disease (MRD)-negative CR, perhaps obviating the need for reinduction as well as limiting relapse without undue toxicity. Methods: The primary objective of this phase 1 study was to determine the maximum tolerated dose (MTD) of VEN plus "3+7" induction and cytarabine-based consolidation therapy in previously untreated AML pts. Pt eligibility includes previously untreated AML, Results: Two of the first 6 pts on VEN 200 experienced DLTs (rapidly resolving grade 4 DIC after a single dose of VEN 50 mg and death at day 14 of sepsis in a 73 year old man). Given 2/6 DLT events, an amendment allowed further accrual at the starting dose of VEN 200 mg but restricted accrual to age 18-60 years. All 3 pts on the expanded cohort and 3/3 at the 400 mg cohort have responded, and none experienced a DLT. The trial expanded to treat pts with 600 mg of VEN, but a 24 yo F experienced a septic death on day 9. Therefore, the 400 mg dose level was determined to be the MTD. At the VEN 200 dose level (n=7), the median time to ANC recovery ≥ 0.5K/ul and platelet recovery ≥ 50 K/ul was 33 days (range 24-38) and 29 days (range 17-55), respectively; at VEN 400 (n=3) 29 days (range 22-34) and 24 days (23-25), respectively. All 10 evaluable pts responded (9CR/1CRi); each achieved CR with a single induction cycle. 6/8 assessed achieved MRD negativity by flow cytometry. The table lists the specific pt characteristics, adverse events and outcome. Conclusions: VEN 400 mg/d d1-11 with "3+7" induction starting on d 2 can be given safely in pts age 18-60 with newly diagnosed AML. The regimen appears highly active. Moving forward, pts will be treated with 3+7/VEN 400 induction followed by high dose cytarabine starting on day 2 plus VEN 200 (and 400 or 600 potential cohorts) d1-8. Prophylactic anti-gut flora antibiotics will accompany all courses. The 3+7/VEN 400 induction regimen derived from this trial will be compared to 3+7 in non-favorable risk newly diagnosed AML pts ages 18-60 and VEN/high dose cytarabine post-remission therapy evaluated in the context of North American Intergroup studies. Table Disclosures Stone: Stemline: Consultancy; Astellas: Consultancy; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB; Syntrix: Other: DSMB; Syndax: Consultancy, Research Funding; Trovagene: Consultancy; Biolinerx: Consultancy; Macrogenics: Consultancy; Argenix: Other; Jazz: Consultancy; Janssen: Consultancy; Aztra-Zeneca: Consultancy; Celgene: Consultancy, Other; Pfizer: Consultancy; Daiichi-Sankyo: Consultancy; Arog: Consultancy, Research Funding; Gemoab: Consultancy; Syros: Consultancy; Abbvie: Consultancy, Research Funding. DeAngelo:Forty-Seven: Consultancy; Blueprint Medicines Corporation: Consultancy, Research Funding; Agios: Consultancy; Autolos: Consultancy; Amgen: Consultancy; Incyte Corporation: Consultancy; Glycomimetics: Research Funding; Abbvie: Research Funding; Takeda: Consultancy; Shire: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Research Funding; Jazz: Consultancy. Letai:Dialectic: Membership on an entity's Board of Directors or advisory committees; Flash Therapeutics: Membership on an entity's Board of Directors or advisory committees; Zentalis: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; AbbVie: Consultancy; Novartis: Research Funding; Chugai: Other: Lecture Fees. Konopleva:Ablynx: Research Funding; Calithera: Research Funding; Rafael Pharmaceutical: Research Funding; Cellectis: Research Funding; AstraZeneca: Research Funding; Forty-Seven: Consultancy, Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Agios: Research Funding; Amgen: Consultancy; Kisoji: Consultancy; F. Hoffmann La-Roche: Consultancy, Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Ascentage: Research Funding; Eli Lilly: Research Funding; Sanofi: Research Funding; AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Garcia:Genentech: Research Funding; Eli Lily: Research Funding; Pfizer: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Venetoclax used with standard AML induction therapy

Daily low-dose interleukin-2 (IL-2) at a fixed dose of 1 × 106 IU/m2/day leads to preferential expansion of CD4+CD25+CD127-Foxp3+ regulatory T cells (Treg) and clinical responses in 50-60% of adult patients with steroid-refractory chronic GVHD. During fixed-dose IL-2 therapy, plasma IL-2 levels rise rapidly, but decrease over time despite continued daily administration. Lower IL-2 levels correlate with decreased Treg proliferation, possibly due to IL-2 sequestration via binding to high-affinity IL-2 receptors on Treg. We reasoned that IL-2 dose escalation at the time of anticipated fall in plasma IL-2 levels would avoid tachyphylaxis and enhance Treg expansion. We conducted a phase 1 trial of individual patient IL-2 dose escalation over 8 weeks in adult and pediatric patients with steroid-refractory cGVHD. Daily SC IL-2 was initiated at 0.67 × 106 and 0.33 × 106 IU/m2/day in the adult and pediatric cohorts, respectively. Each participant had dose escalations at weeks 2 and 4 to a maximum dose of 2 × 106 IU/m2/day in adults and 1 × 106 IU/m2/day in children. We studied 21 participants (10 adult, 11 children) with median ages of 57 (range, 33-71) and 12 years (range, 3-22) in the adult and pediatric cohorts, respectively. The cohorts did not differ in terms of time since cGVHD onset, number of organ sites involved or failed therapies prior to enrollment. Individually dose-escalated IL-2 was well tolerated in children with 1 patient requiring dose reduction for electrolyte imbalances. In the adult cohort, 1 patient withdrew for cGVHD progression, 4 required dose reduction for injection site reactions and 2 were unevaluable. At week 8, objective cGVHD responses (PR) were seen in 8 of 11 pediatric patients (73%), but in only 1 of 8 evaluable adult patients (13%). Response sites included skin (n=4), joint/fascia/muscle (n=1), lung (n=5), and GI tract (n=2). 11 pediatric and 4 adult participants with clinical benefit (PR or SD with minor response) continued extended duration IL-2 therapy. 9 pediatric patients on IL-2 therapy were able to wean steroid therapy with a median dose reduction of 67% at 6 months (Fig. 1). Children had a superior immunologic response despite lower IL-2 doses. The median Treg:Tcon ratio at week 8 was significantly higher in the pediatric cohort (0.42 vs 0.21, p = 0.02). Both cohorts had increased NK cell numbers, with no significant changes in CD4Tcon, CD8 T cell or B cells (Fig. 2). Pediatric patients had greater thymic output of naive Treg as well as a larger fraction of PD-1-expressing effector memory Treg at baseline and during IL-2 therapy (Fig. 3), which has been correlated with improved Treg expansion and survival. We show for the first time that low-dose IL-2 is safe in children with advanced steroid-refractory cGVHD and results in a high clinical response rate. In adults, dose escalation above fixed-dose MTD did not improve Treg expansion or clinical response relative to fixed daily dosing.

Background: Current chemotherapy regimens in children with acute lymphoblastic leukemia (ALL) produce disease-free survival (DFS) rates of greater than 80%. In contrast, adults with ALL have a much poorer prognosis, with DFS rates of 40%, and less than 20% for patients over 60 years of age. The oral BCL2 inhibitor venetoclax has improved response rates in older patents with AML who are not candidates for standard induction chemotherapy. Furthermore, BH3 profiling and protein analysis has shown that ALL cell lines and primary cells exhibit BCL-2 dependence, supporting clinical trials of BCL-2 antagonists in ALL (Del Gaizo Moore et al Blood 2008; Benito et al Cell Rep 13:2715, 2015). This phase I trial was performed to determine if venetoclax can be safely added to a reduced intensity chemotherapy regimen for older adults with untreated ALL and in patients with R/R ALL. Methods: Patients (pts) over 60 yrs or older with untreated, Philadelphia chromosome negative ALL were eligible. After the first 6 pts were enrolled, the study was amended to allow enrollment of adults 18 yrs or older with R/R ALL. The primary objective of this study was to determine the feasibility of a 21-day schedule of venetoclax with the mini-hyper-CVD chemotherapy regimen. The therapeutic backbone of this protocol was based on a lower intensity version of hyper-CVAD with no anthracycline (Kantarjian et al Lancet Oncol 2018). Two dose levels of venetoclax were tested, 400 mg and 600 mg for 21 days of each cycle. The induction chemotherapy consisted of mini-hyper fractionated cyclophosphamide, vincristine, dexamethasone, alternating with cycles of methotrexate and cytarabine. Two doses of intrathecal chemotherapy were administered per cycle during the first four cycles. Upon completion of induction/consolidation chemotherapy, patients could receive an allogeneic stem cell transplant (SCT) or receive venetoclax plus POMP maintenance chemotherapy. Bone marrow and peripheral blood samples were collected for BH3 profiling and CyTOF to measure Bcl-2 family expression. The analysis is ongoing and will be reported. Results: To date 18 pts were enrolled. Three pts at dose level 1 (400 mg), 6 pts at dose level 2 (600 mg; the highest dose tested) and 9 pts in the expansion cohort (600 mg), which is the recommended phase II dose (RP2D). There has been no protocol defined DLTs. The median age was 65 yrs, (range, 23-82), 78% were male, 56% B-lineage, 56% were previously untreated. For the older de novo pts, 7 had B-ALL with 5 pts with haploid/near triploid cytogenetics and TP53 mutations. Two pts had ETP-ALL and 1 pt with mature T-ALL. In this group of untreated de novo pts, the overall response rate (ORR) rate was 100% with 9/10 (90%) achieving CR and 1 pt PR (Table 1 and Figure 1). All CR pts achieved an MRD negative status by multicolor flow cytometry with a sensitivity of 0.01%. Of the 10 pts with de novo ALL, 4 pts remain on treatment, and 6 pts went to SCT. The median follow up for the de novo pts was 11.3 mos (range, 2.0-17.8) and the median duration of response for these patients was 9.9 mos (range 0.9, 15.7). There have been no relapses thus far in the de novo ALL cohort. For the R/R pts, the median number of prior regimens was 2.5 (range 1-5) and the CR/CRp rate was 3/8 (37.5%) with 2 pts MRD negative (25%). Of the 8 pts with R/R ALL, 2 pts remain on treatment. For all 18 pts, the grade 3 adverse events included febrile neutropenia (39%), hyperglycemia (17%) and hypocalcemia (11%). There were two grade 4 events, pneumonia and sepsis, and no grade 5 events. Conclusions: The administration of venetoclax with a reduced intensity chemotherapy regimen (mini-hyper-CVD) was safe and well tolerated. The RP2D dose was 600 mg daily for 21 days per cycle. This regimen was particularly well tolerated in the older previously untreated ALL population. Although the CR and MRD negative rates were exceptionally high for the older adult cohort, longer follow up and larger studies are needed. The addition of venetoclax may represent a major therapeutic advance in older adults with ALL. Disclosures Jain: Cellectis: Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stevenson:Celgene: Research Funding. Winer:Jazz Pharmaceuticals, Pfizer: Consultancy. Garcia:Genentech: Research Funding; Abbvie: Research Funding. Stone:Arog: Consultancy, Research Funding; Otsuka: Consultancy; Biolinerx: Consultancy; Takeda: Other: DSMB; Trovagene: Consultancy; Novartis: Consultancy, Research Funding; Biosight: Consultancy; Agios: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Argenix: Other: DSMB; Amgen: Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy, Research Funding; Stemline: Consultancy; Agios: Consultancy, Research Funding; Otsuka: Consultancy; Argenix: Other: DSMB; Roche: Consultancy; Macrogenics: Consultancy; Astra-Zeneca: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Jazz: Consultancy; Biolinerx: Consultancy; Daiichi-Sankyo: Consultancy; Astellas: Consultancy; Daiichi-Sankyo: Consultancy; Celgene: Consultancy, Other: DSMB; Actinium: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Arog: Consultancy, Research Funding; Trovagene: Consultancy; Otsuka: Consultancy; Argenix: Other: DSMB; Novartis: Consultancy, Research Funding; Stemline: Consultancy; Takeda: Other: DSMB; Agios: Consultancy, Research Funding; Jazz: Consultancy; Astra-Zeneca: Consultancy; Arog: Consultancy, Research Funding; Roche: Consultancy; Macrogenics: Consultancy; Otsuka: Consultancy; Biosight: Consultancy; Abbvie: Consultancy, Research Funding; Biolinerx: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Argenix: Other: DSMB; Biolinerx: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Celgene: Consultancy, Other: DSMB; Actinium: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding. Jabbour:Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding. Ravandi:Macrogenix: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Cyclacel LTD: Research Funding. Kantarjian:Astex: Research Funding; Daiichi-Sankyo: Research Funding; Immunogen: Research Funding; Cyclacel: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; Novartis: Research Funding; Agios: Honoraria, Research Funding; Ariad: Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Pfizer: Honoraria, Research Funding. Neuberg:Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Equity Ownership; Celgene: Research Funding. Letai:AbbVie, AstraZeneca, Novartis: Consultancy, Research Funding; Zeno Pharmaceuticals, Vivid Bioscience, Flash Therapeutics, Dialectic Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Cofounder or Advisory Board member. Konopleva:Agios: Research Funding; Astra Zeneca: Research Funding; Ablynx: Research Funding; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Kisoji: Consultancy, Honoraria; Ascentage: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Calithera: Research Funding; Genentech: Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Cellectis: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding. DeAngelo:Abbvie: Research Funding; Glycomimetics: Research Funding; Amgen, Autolus, Celgene, Forty-seven, Incyte, Jazzs, Pfizer, Shire, Takeda: Consultancy; Blueprint: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. OffLabel Disclosure: Venetoclax for patients with acute lymphoblastic leukemia.

Background: Although daunorubicin/cytarabine ("3+7")-based chemotherapy (CT) regimens produce complete remission (CR) rates of approximately 70% in younger adults, about 30% require re-induction. Among those achieving CR, relapse after post-remission intensive CT or allogeneic transplant is common and limits cure. Venetoclax (VEN) is an orally available selective BCL-2 inhibitor that promotes mitochondrial-mediated apoptosis in myeloblasts during cytotoxic stress. VEN in combination with hypomethylating agents and low dose cytarabine in untreated unfit elderly AML patients (pts) elicits high response and led to drug approval in that setting. VEN in combination with standard '3+7" could lead to a higher rate of measurable residual disease (MRD)-negative CR, perhaps obviating the need for reinduction as well as limiting relapse after consolidation therapy without undue toxicity. Methods: The primary objective of this phase 1 study is to determine the maximum tolerated dose of VEN that can be given in combination with standard intensive induction (ind) and consolidation CT in previously untreated AML pts. Pt eligibility includes no prior treatment (rx) for AML, FLT3 wild type, non-inv16 or t(8; 21) AML, either de novo or secondary. Pts must not require strong CYP3A inhibitors/inducers, have normal organ function, have WBC=18 (study amended to include only those age 18-60 after the first 6 pts were treated). VEN is given during ind on days 1-11 in cohorts of 200, 400, and 600 mg/d/ (after 4 d ramp-up) with daunorubicin 60 mg/m2/d IVP days 2-4 and cytarabine 200 mg/m2/d by IVCI days 2-8. A day 15 marrow determines the need for a second ind consisting of the same doses of VEN, daunorubicin and cytarabine given on days 1-8, 2-3, and 2-6, respectively. VEN escalation is carried out in 3+3 fashion. Once the MTD for VEN during ind is determined pts will be treated at that dose during ind and remitting pts given escalating doses (cohorts of 200, 400, 600 mg) of VEN d1-8 in a 3+3 fashion (beginning at one dose level below the MTD (or 100 mg if 200 mg is determined to the ind MTD)) with a single cycle of cytarabine 3g/m2 over 3h q 12 h on days 1, 3, and 5. A 10 pt confirmation cohort will be accrued at the MTD. Dose-limiting toxicity (DLT) is defined as any death, delayed neutrophil recovery (failure to achieve absolute neutrophil count (ANC) ≥ 500/mL by day 42 in pts without residual AML), or any gr 4 non-heme non-resolving toxicity not clearly due to CT alone. A marrow exam, including an assessment of MRD by multiparameter flow cytometry with a sensitivity of 0.02%, is carried out at the time of count recovery during induction but no later than day 42. Correlative studies include flow cytometry-based BH3 profiling (Vo TT, Cell, 2012) on blasts obtained at enrollment and just prior to chemo and CyTof to characterize BCL-2-associated proteins. Results: The first pt treated (58 yo F with normal karyotype, and NGS panel showing a DNMT3A mutation, though subsequent PCR-based assay disclosed a FLT3 ITD) developed gr 4 DIC after the first dose of VEN 50 mg (required factor replacement for elevated INR, but had no bleeding). VEN was stopped and she achieved an MRD negative CR with standard ind, but the first cohort was expanded to 6 pts. 4 of the 5 additional pts achieved a CR, but a 73 year old man died of nadir sepsis at d 14. Given 2/6 DLT events, VEN 200 was considered unacceptable by protocol design. An amendment allowed further accrual at the starting dose of VEN 200 mg but restricted accrual to age 18-60. All 3 pts on the expanded cohort have responded, and none experienced a DLT, so accrual to the VEN 400 mg cohort is now beginning. None of the pts required a second ind course and no tumor lysis was seen. The median time to ANC and platelet recovery to 1K/ul and 100K/ul in the 7 pts who received all planned VEN is 36 d (range 24-43) and 27 d (range 24-55), respectively. The table lists the specific pt characteristics, adverse events and outcome. Conclusions: We have preliminarily shown that VEN 200 mg/d beginning one d prior and until three d after 3+7 ind can be given safely in pts age 18-60; escalation to VEN 400 mg is ongoing. Flow based MRD-negative remissions have been noted after a single ind cycle. Plans are underway to compare the VEN/3+7 ind regimen derived from this trial to 3+7 in non-favorable risk newly diagnosed AML pts ages 18-60 in the context of a North American Intergroup study. Table Disclosures Stone: Novartis: Consultancy, Research Funding; Macrogenics: Consultancy; Astra-Zeneca: Consultancy; Arog: Consultancy, Research Funding; Arog: Consultancy, Research Funding; Otsuka: Consultancy; Agios: Consultancy, Research Funding; Actinium: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Other: DSMB; Daiichi-Sankyo: Consultancy; Astellas: Consultancy; Otsuka: Consultancy; Biolinerx: Consultancy; Argenix: Other: DSMB; Amgen: Membership on an entity's Board of Directors or advisory committees; Argenix: Other: DSMB; Stemline: Consultancy; Biosight: Consultancy; Roche: Consultancy; Takeda: Other: DSMB; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Pfizer: Consultancy; Trovagene: Consultancy; Biolinerx: Consultancy; Jazz: Consultancy; Trovagene: Consultancy. DeAngelo:Incyte: Consultancy; Amgen: Consultancy; Jazz Pharmaceuticals Inc: Consultancy; Celgene: Consultancy; GlycoMimetics: Research Funding; Blueprint: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Shire: Consultancy; Takeda Pharmaceuticals: Consultancy; Abbvie: Research Funding. Galinsky:Merus Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; ABIM: Other: Member on specialty oncology board. Letai:AbbVie, AstraZeneca, Novartis: Consultancy, Research Funding; Zeno Pharmaceuticals, Vivid Bioscience, Flash Therapeutics, Dialectic Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Cofounder or Advisory Board member. Konopleva:Kisoji: Consultancy, Honoraria; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Astra Zeneca: Research Funding; Agios: Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding. OffLabel Disclosure: Venetoclax is being used off label in combination with standard and induction and consolidation chemotherapy in AML