TY - JOUR
T1 - Clinical Experience With Venetoclax Combined With Chemotherapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia
AU - Richard-Carpentier, Guillaume
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Rausch, Caitlin R.
AU - Savoy, Jonathan M.
AU - Bose, Prithviraj
AU - Yilmaz, Musa
AU - Jain, Nitin
AU - Borthakur, Gautam
AU - Ohanian, Maro
AU - Alvarado, Yesid
AU - Rytting, Michael
AU - Kebriaei, Partow
AU - Konopleva, Marina
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
N1 - Funding Information:
E.J. reports research grants and advisory roles with Takeda, AbbVie, United States, Pfizer, United States, Amgen, United States, Adaptive Biotechnologies, and Bristol-Myers Squibb, United States. N.J. reports research grants and honoraria from Pharmacyclics, United States, AstraZeneca, United Kingdom, Genentech, Verastem, Pfizer, United States, Servier, France, ADC Therapeutics, Precision Biosciences, Adaptive Biotechnologies, and AbbVie, United States; research grants from Bristol-Myers Squibb, United States, Celgene, Seattle Genetics, Incyte, Cellectis; and honoraria from Janssen. G.B. reports research grants from GlaxoSmithKline, Janssen Scientific Affairs, LLC, Eli Lilly and Co, Cyclacel, Inc, AstraZeneca, United Kingdom, Incyte Corp, AbbVie, United States, Oncoceutics Inc, Bioline Rx, Novartis, Switzerland, Eisai, Japan, Arvinas Inc, Cantargia AB, and PTC Therapeutics, United States. M.K. reports research funding and advisory roles with AbbVie, United States, Genentech, United States, and Hoffman-La Roche, Switzerland. H.K. reports research funding and honoraria from AbbVie, United States, Agios, Amgen, United States, Immunogen, and Pfizer; research funding from Ariad, Astex, Bristol-Myers Squibb, United States, Cyclacel, Daiichi-Sankyo, Japan, Jazz Pharma, and Novartis, Switzerland; and honoraria from Actinium and Takeda. F.R. reports research funding and honoraria from AbbVie, United States and honoraria from Novartis, Switzerland. The remaining authors have stated that they have no conflicts of interest.
Funding Information:
E.J. reports research grants and advisory roles with Takeda , AbbVie, United States , Pfizer, United States , Amgen, United States , Adaptive Biotechnologies , and Bristol-Myers Squibb, United States . N.J. reports research grants and honoraria from Pharmacyclics, United States , AstraZeneca, United Kingdom , Genentech , Verastem , Pfizer, United States , Servier, France , ADC Therapeutics , Precision Biosciences , Adaptive Biotechnologies , and AbbVie, United States ; research grants from Bristol-Myers Squibb, United States , Celgene, Seattle Genetics , Incyte , Cellectis ; and honoraria from Janssen. G.B. reports research grants from GlaxoSmithKline , Janssen Scientific Affairs , LLC , Eli Lilly and Co , Cyclacel, Inc , AstraZeneca, United Kingdom , Incyte Corp , AbbVie, United States , Oncoceutics Inc , Bioline Rx , Novartis, Switzerland , Eisai, Japan , Arvinas Inc , Cantargia AB , and PTC Therapeutics, United States . M.K. reports research funding and advisory roles with AbbVie, United States , Genentech, United States , and Hoffman-La Roche, Switzerland . H.K. reports research funding and honoraria from AbbVie, United States , Agios , Amgen, United States , Immunogen , and Pfizer ; research funding from Ariad , Astex , Bristol-Myers Squibb, United States , Cyclacel , Daiichi-Sankyo, Japan , Jazz Pharma , and Novartis, Switzerland ; and honoraria from Actinium and Takeda. F.R. reports research funding and honoraria from AbbVie, United States and honoraria from Novartis, Switzerland. The remaining authors have stated that they have no conflicts of interest.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - 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. 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.
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. 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.
KW - Early T-cell precursor ALL
KW - Myelosuppression
KW - Remission
KW - Survival
KW - Treatment
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U2 - 10.1016/j.clml.2019.09.608
DO - 10.1016/j.clml.2019.09.608
M3 - Article
C2 - 32035785
AN - SCOPUS:85078955515
SN - 2152-2650
VL - 20
SP - 212
EP - 218
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -