PMID- 32035785 OWN - NLM STAT- MEDLINE DCOM- 20210531 LR - 20210531 IS - 2152-2669 (Electronic) IS - 2152-2669 (Linking) VI - 20 IP - 4 DP - 2020 Apr TI - Clinical Experience With Venetoclax Combined With Chemotherapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia. PG - 212-218 LID - S2152-2650(19)31995-0 [pii] LID - 10.1016/j.clml.2019.09.608 [doi] AB - BACKGROUND: Patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) have dismal outcomes. Preclinical studies have suggested that T-ALL cells are sensitive to BCL2 inhibition. The clinical activity of venetoclax, a selective BCL2 inhibitor, in T-ALL is unknown. PATIENT AND METHODS: We retrospectively reviewed the efficacy and safety of venetoclax combined with chemotherapy for patients with R/R T-ALL treated at our institution. RESULTS: Thirteen patients with R/R T-ALL with a median age of 46 years (range, 20-75 years) were treated with venetoclax plus chemotherapy. Five patients (38%) had early T-cell precursor ALL. The patients had received a median of 2 previous lines of therapy (range, 1-11). Venetoclax at a median dose of 200 mg/d for 21 days, generally with a concomitant azole antifungal, was combined with various agents, including hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), asparaginase, nelarabine, decitabine, or other intensive chemotherapy. Of the 10 patients evaluable for bone marrow response, 6 (60%) achieved a remission with bone marrow blasts < 5%, including 3 with complete hematologic recovery. The median overall survival and relapse-free survival were 7.7 and 4.0 months, respectively. No early death or clinically significant tumor lysis syndrome were reported. The median interval to neutrophil recovery and platelet recovery were 15 days and 44 days, respectively, with prolonged cytopenias observed with venetoclax 400 mg/d or when given for > 14 days per cycle. CONCLUSION: Combination therapy with venetoclax showed promising clinical efficacy in R/R T-ALL. Further studies are warranted to evaluate the clinical benefit of BCL2 inhibitors in T-ALL. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Richard-Carpentier, Guillaume AU - Richard-Carpentier G AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Jabbour, Elias AU - Jabbour E AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Short, Nicholas J AU - Short NJ AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Rausch, Caitlin R AU - Rausch CR AD - Department of Clinical Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Savoy, Jonathan M AU - Savoy JM AD - Department of Clinical Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Bose, Prithviraj AU - Bose P AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Yilmaz, Musa AU - Yilmaz M AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Jain, Nitin AU - Jain N AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Borthakur, Gautam AU - Borthakur G AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Ohanian, Maro AU - Ohanian M AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Alvarado, Yesid AU - Alvarado Y AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Rytting, Michael AU - Rytting M AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Kebriaei, Partow AU - Kebriaei P AD - Department of Cellular Therapy and Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Konopleva, Marina AU - Konopleva M AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Kantarjian, Hagop AU - Kantarjian H AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Ravandi, Farhad AU - Ravandi F AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: fravandi@mdanderson.org. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20190930 PL - United States TA - Clin Lymphoma Myeloma Leuk JT - Clinical lymphoma, myeloma & leukemia JID - 101525386 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Sulfonamides) RN - 5J49Q6B70F (Vincristine) RN - 7S5I7G3JQL (Dexamethasone) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - N54AIC43PW (venetoclax) RN - CVAD protocol SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Bridged Bicyclo Compounds, Heterocyclic/*administration & dosage MH - Cyclophosphamide/administration & dosage MH - Dexamethasone/administration & dosage MH - Disease-Free Survival MH - Doxorubicin/administration & dosage MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/blood/drug therapy/mortality MH - Sulfonamides/*administration & dosage MH - Survival Rate MH - Vincristine/administration & dosage OTO - NOTNLM OT - Early T-cell precursor ALL OT - Myelosuppression OT - Remission OT - Survival OT - Treatment EDAT- 2020/02/10 06:00 MHDA- 2021/06/01 06:00 CRDT- 2020/02/10 06:00 PHST- 2019/06/15 00:00 [received] PHST- 2019/08/07 00:00 [revised] PHST- 2019/09/20 00:00 [accepted] PHST- 2020/02/10 06:00 [pubmed] PHST- 2021/06/01 06:00 [medline] PHST- 2020/02/10 06:00 [entrez] AID - S2152-2650(19)31995-0 [pii] AID - 10.1016/j.clml.2019.09.608 [doi] PST - ppublish SO - Clin Lymphoma Myeloma Leuk. 2020 Apr;20(4):212-218. doi: 10.1016/j.clml.2019.09.608. Epub 2019 Sep 30.