Session: 732. Clinical Allogeneic Transplantation: Results: Poster III
Hematology Disease Topics & Pathways:
Biological, Adult, AML, bone marrow, Diseases, Therapies, Adverse Events, Study Population, Clinically relevant, Myeloid Malignancies, transplantation, stem cells
Methods: We conducted a retrospective analysis of 35 AML/ALL pts who received alloSCT following venetoclax-based therapies between 2013-2018 at MD Anderson Cancer Center.
Results: Median age at alloSCT was 60 years and 23 (66%) pts had an age-adjusted HCT-CI score > 3. Disease diagnosis – AML (n=31; 89%), ALL (n=4; 11%). Disease status in pts with AML at study entry was CR1 (n=11; 35%), CR2/CR3 (n=6; 19%), Cri (n=2, 6%), hypoplastic marrow (n=2; 6%) or refractory disease (n=10; 32%). ALL pts were in CR1 (n=2) or CR2 (n=2). Sixteen (46%) pts were MRD-negative by flow cytometry on marrow samples pre-alloSCT, 7 (20%) were MRD-positive, and 10 (29%) had active disease; 2 pts had hypoplastic marrow. Median lines of prior therapies was 2 (range 1-7) and 6 (17%) pts had failed a prior alloSCT. Disease risk index was intermediate (n=18 of 34; 53%) or high/very-high (n=16 of 34; 47%). Venetoclax was provided in combination of hypomehylating (HMA) agents or other chemotherapies in 26 (74%) and 9 (26%) pts, respectively. Median duration of venetoclax-based treatment was 2.0 months (range 0.5- 4.6). Most pts (83%) continued their therapy as a bridge to alloSCT. Venetoclax was discontinued in 6 (17%) pts due to adverse events (n=4) or progression (n=2). Conditioning regimens were melphalan-based reduced intensity (n=26, 74%), or busulfan-fludarabine regimens (n=9; 26%). Donor source was matched unrelated (n=13, 37%), or related (n=9; 26%); haplo (n=12; 34%) and mismatched unrelated (n=1; 3%). Cell source was from peripheral blood (n=24; 69%) or bone marrow (n=11; 31%). GVHD prophylaxis consisted of tacrolimus with either post-transplant cyclophosphamide in 25 (71%) pts or methotrexate in 10 (29%) pts. Seven (20%) pts (3 with active disease, 2 MRD-positive and 2 were MRD-negative pre-alloSCT)) received maintenance therapy with agents other than venetoclax (Vidaza=2, Sorafenib =2, SGI =1, Ponatinib =1, Asparginase = 1) post alloSCT at a median of 3 months (range, 2-4 months). Median time to ANC >500 was 15.5 days (range, 10-24), and platelets counts >20 k was 22.5 days (range, 11-46). The cumulative incidence (CI) of acute 2-4 and 3-4 GVHD was 29% and 9%, respectively. Risks associated with 100 day-acute 2-4 GVHD were evaluated in univariate analyses. Factors evaluated were age, HCT-CI, # prior lines of therapies, prior alloSCT, type GVHD prophylaxis, donor type, cell source, female donor to male recipients, prior PD-1 therapy (n=3) , types of combination of venetoclax duration of treatment and timing of last venetoclax treatment to alloSCT. Only venetoclax timing to alloSCT was associated with significant risk. The CI of acute 2-4 GVHD in patients who discontinued venetoclax ≤ 2 weeks (n=11, 31%) vs > 2 weeks (n=24, 69%) was 55% vs 17% (P = 0.020; Figure 1), respectively [HR 0.24, 95% confidence interval 0.07-0.80; P = 0.020). . With a median follow up among surviving pts of 18.4 months (range 3.5-31.4), the 1-year rates of OS, PFS, and NRM were 72%, 57% and 12% respectively. Twelve patients died: 8 due to progression, 2 of GVHD, 1 of infection and 1 of unknown cause. Disease status was the only predictor of OS in univariate analysis. Pts who were MRD-negative pre-alloSCT had a 1-year OS of 92% while the 1-year OS in pts who were CR/MRD+ and those with active disease was 38% and 70%, respectively (Figure 2). No factor evaluated was significantly associated with NRM. Conclusions: Our data show that the use of venetoclax-based therapy as a bridge to alloSCT does not increase the risk of NRM or delayed engraftment. It does improve OS by inducing CR/MRD-negativity in high-risk acute leukemia. It may be prudent however to discontinue therapy > 2 weeks before alloSCT in order to avoid a higher risk of acute GVHD.
Disclosures: Jabbour: BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding. Daver: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Konopleva: Cellectis: 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; F. Hoffmann La-Roche: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sanofi: Research Funding; Eli Lilly: Research Funding; Rafael Pharmaceutical: Research Funding; Ascentage: Research Funding; Agios: Research Funding; Amgen: Consultancy; Genentech: Consultancy, Research Funding; Kisoji: Consultancy; Ablynx: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; AstraZeneca: Research Funding; Calithera: Research Funding; Forty-Seven: Consultancy, Research Funding. DiNardo: Daiichi Sankyo: Consultancy, Honoraria, Research Funding; ImmuneOnc: Honoraria, Research Funding; Novartis: Consultancy; MedImmune: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Notable Labs: Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria; Takeda: Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Calithera: Research Funding. Ravandi: Orsenix: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding. Kadia: Pulmotec: Research Funding; Astra Zeneca: Research Funding; Genentech: Honoraria, Research Funding; Cellenkos: Research Funding; Celgene: Research Funding; Amgen: Research Funding; Ascentage: Research Funding; Novartis: Honoraria; Incyte: Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astellas: Research Funding; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding. Alousi: Incyte: Honoraria, Research Funding; Alexion: Honoraria; Therakos: Research Funding. Oran: Arog Pharmaceuticals: Research Funding; Celgene: Consultancy; ASTEX: Research Funding. Kebriaei: Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Jazz: Consultancy. Popat: Bayer: Research Funding; Novartis: Research Funding. Kantarjian: Aptitute Health: Honoraria; BioAscend: Honoraria; Adaptive biotechnologies: Honoraria; Novartis: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Oxford Biomedical: Honoraria; Immunogen: Research Funding; BMS: Research Funding; Ascentage: Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Jazz: Research Funding; Janssen: Honoraria; Delta Fly: Honoraria; Daiichi-Sankyo: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Champlin: Omeros: Consultancy; Actinium: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Genzyme: Speakers Bureau; Takeda: Patents & Royalties; Johnson and Johnson: Consultancy. Khouri: Bristol Myers Squibb: Research Funding; Pfizer: Research Funding.
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