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

Abstract

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.

• Authors: Guillaume Richard-Carpentier, Elias Jabbour, Nicholas J Short, Caitlin R Rausch, Jonathan M Savoy, Prithviraj Bose, Musa Yilmaz, Nitin Jain, Gautam Borthakur, Maro Ohanian, Yesid Alvarado, Michael Rytting, Partow Kebriaei, Marina Konopleva, Hagop Kantarjian, Farhad Ravandi
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 20 Issue 4 Pg. 212-218 (04 2020) ISSN: 2152-2669 [Electronic] United States
• PMID: 32035785 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Sulfonamides
• Vincristine
• Dexamethasone
• Doxorubicin
• Cyclophosphamide
• venetoclax

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Bridged Bicyclo Compounds, Heterocyclic (administration & dosage)
• Cyclophosphamide (administration & dosage)
• Dexamethasone (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Female
• Humans
• Male
• Middle Aged
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (blood, drug therapy, mortality)
• Sulfonamides (administration & dosage)
• Survival Rate
• Vincristine (administration & dosage)