Clinical Experience With Venetoclax Combined With Chemotherapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia

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. We retrosp...

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Published in:Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2020-04, Vol.20 (4), p.212-218
Main Authors: Richard-Carpentier, Guillaume, Jabbour, Elias, Short, Nicholas J., Rausch, Caitlin R., Savoy, Jonathan M., Bose, Prithviraj, Yilmaz, Musa, Jain, Nitin, Borthakur, Gautam, Ohanian, Maro, Alvarado, Yesid, Rytting, Michael, Kebriaei, Partow, Konopleva, Marina, Kantarjian, Hagop, Ravandi, Farhad
Format: Article
Language:English
Subjects:
Early T-cell precursor ALL
Myelosuppression
Remission
Survival
Treatment
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Summary: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. We retrospectively reviewed the efficacy and safety of venetoclax combined with chemotherapy for patients with R/R T-ALL treated at our institution. 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. 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. Combination therapies that included venetoclax were administered to 13 patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma at our institution. Bone marrow responses were achieved in 60% of the evaluable patients, and 2 patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma remained alive in remission. Venetoclax combination therapies are safe, with myelosuppression the main adverse event observed with the addition of venetoclax.
ISSN:2152-2650
2152-2669
DOI:10.1016/j.clml.2019.09.608