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

Richard‐Carpentier, Guillaume; Jabbour, Elias; Rausch, Caitlin R.; Savoy, J. Michael; Bose, Prithviraj; Yılmaz, Musa; Jain, Nitin; Borthakur, Gautam; Ohanian, Maro; Alvarado, Yesid; Rytting, Michael; Kebriaei, Partow; Konopleva, Marina; Kantarjian, Hagop M.; Ravandi, Farhad

doi:10.1016/j.clml.2019.09.608

Cited by 85 publications

(71 citation statements)

References 18 publications

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“…Finally, RPL10 R98S mutant leukemia cells are potentially sensitive to Bcl2 inhibitor venetoclax (88). Venetoclax combined to chemotherapy induced a morphological remission in 60% of patients (including ETP-ALL) in a recent retrospective study (103).…”

Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

et al. 2020

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Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

et al. 2020

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“…Venetoclax has been approved for patients with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (10) and has been reported to be clinically active in patients with relapsed/refractory early T-cell precursor ALL (ETP-ALL), an ALL subtype associated with poor prognosis (22,23). Navitoclax has been assessed in early clinical studies across lymphoid malignancies (24,25).…”

Section: Introductionmentioning

confidence: 99%

Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

et al. 2021

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Combining venetoclax, a selective BCL-2 inhibitor, with low-dose navitoclax, a BCL-X L /BCL-2 inhibitor, may allow targeting of both BCL-2 and BCL-X L without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adultequivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population. Statement of Significance In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histological and genomic subtypes and in those who failed available therapies including stem cell transplant. Research.

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“…Still fewer data exist on the use of venetoclax plus HMA in relapsed T-cell leukemias [ 12 ]. A series of 12 patients with relapsed T-cell leukemia treated with venetoclax plus various chemotherapies (included an HMA in 3) was recently published and showed an impressive response rate of 60% [ 13 ]. In addition, emerging data from recent and ongoing clinical trials have shown promising outcomes with venetoclax and an HMA in cases of acute myeloid leukemia with an IDH1/2 mutation; this may have particular relevance to our case in which a mutation in IDH1 was detected at diagnosis [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The regimen was a successful bridge to 2 nd allo-SCT and well-tolerated aside from prolonged cytopenias in the setting of repeated prior cytotoxic chemotherapy regimens. Regimens for MPAL are typically designed to treat both myeloid and lymphoid lineages; therefore, based on publications of retrospective series to date, venetoclax plus HMA offers a promising novel approach to this clinically challenging entity [ 11 , 13 ]. Future research is required to further explore this strategy and combine venetoclax with other agents active in T/myeloid MPAL.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)

Klocke

Dong

O'Brien

et al. 2020

Case Reports in Hematology

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T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS) is an uncommon and aggressive leukemia without well-established treatment guidelines, particularly when relapsed. Venetoclax plus a hypomethylating agent offers a promising option in this situation since studies support its use in both acute myeloid and, albeit with fewer data to date, acute T-cell-lymphoblastic leukemias. We report the successful eradication of T/myeloid MPAL NOS relapsed after allogeneic stem cell transplant with venetoclax plus decitabine. A consolidative allogeneic stem cell transplant from a second donor was subsequently performed, and the patient remained without evidence of disease more than one year later. Further investigation is indicated to evaluate venetoclax combined with hypomethylating agents and/or other therapies for the management of T/myeloid MPAL NOS.

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

Cited by 85 publications

References 18 publications

The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)

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