Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active.

Autor:	Garcia JS; Department of Medical Oncology, and., Kim HT; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA; and., Murdock HM; Department of Medicine., Cutler CS; Department of Medical Oncology, and., Brock J; Department of Medical Oncology, and., Gooptu M; Department of Medical Oncology, and., Ho VT; Department of Medical Oncology, and., Koreth J; Department of Medical Oncology, and., Nikiforow S; Department of Medical Oncology, and., Romee R; Department of Medical Oncology, and., Shapiro R; Department of Medical Oncology, and., Loschi F; Department of Medical Oncology, and., Ryan J; Department of Medical Oncology, and., Fell G; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA; and., Karp HQ; Department of Medical Oncology, and., Lucas F; Department of Pathology, Brigham and Women's Hospital, Boston, MA., Kim AS; Department of Pathology, Brigham and Women's Hospital, Boston, MA., Potter D; Department of Medical Oncology, and., Mashaka T; Department of Medical Oncology, and., Stone RM; Department of Medical Oncology, and., DeAngelo DJ; Department of Medical Oncology, and., Letai A; Department of Medical Oncology, and., Lindsley RC; Department of Medical Oncology, and., Soiffer RJ; Department of Medical Oncology, and., Antin JH; Department of Medical Oncology, and.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2021 Dec 28; Vol. 5 (24), pp. 5536-5545.
DOI:	10.1182/bloodadvances.2021005566
Abstrakt:	Adding the selective BCL-2 inhibitor venetoclax to reduced-intensity conditioning chemotherapy (fludarabine and busulfan [FluBu2]) may enhance antileukemic cytotoxicity and thereby reduce the risk of posttransplant relapse. This phase 1 study investigated the recommended phase 2 dose (RP2D) of venetoclax, a BCL-2 selective inhibitor, when added to FluBu2 in adult patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and MDS/myeloproliferative neoplasms (MPN) undergoing transplant. Patients received dose-escalated venetoclax (200-400 mg daily starting day -8 for 6-7 doses) in combination with fludarabine 30 mg/m2 per day for 4 doses and busulfan 0.8 mg/kg twice daily for 8 doses on day -5 to day -2 (FluBu2). Transplant related-toxicity was evaluated from the first venetoclax dose on day -8 to day 28. Twenty-two patients were treated. At study entry, 5 patients with MDS and MDS/MPN had 5% to 10% marrow blasts, and 18 (82%) of 22 had a persistent detectable mutation. Grade 3 adverse events included mucositis, diarrhea, and liver transaminitis (n = 3 each). Neutrophil/platelet recovery and acute/chronic graft-versus-host-disease rates were similar to those of standard FluBu2. No dose-limiting toxicities were observed. The RP2D of venetoclax was 400 mg daily for 7 doses. With a median follow-up of 14.7 months (range, 8.6-24.8 months), median overall survival was not reached, and progression-free survival was 12.2 months (95% confidence interval, 6.0-not estimable). In patients with high-risk AML, MDS, and MDS/MPN, adding venetoclax to FluBu2 was feasible and safe. To further address relapse risk, assessment of maintenance therapy after venetoclax plus FluBu2 transplant is ongoing. This study was registered at clinicaltrials.gov as #NCT03613532. (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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