Hannah Goulart, Elias Jabbour, Nicholas J Short, Tapan M Kadia, Naveen Pemmaraju, Koichi Takahashi, Farhad Ravandi, Marina Konopleva, Nitin Jain
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引用次数: 0
Abstract
Background: Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) represents a high-risk subtype of B-ALL. The disease is driven by a range of kinase-activating mutations, resulting in a similar gene expression profile to that of Ph-positive ALL, and one which may be targetable by JAK- or ABL-directed kinase inhibition.
Patients and methods: We conducted a phase I/II trial to explore the safety and efficacy of ruxolitinib or dasatinib in combination with Hyper-CVAD chemotherapy for patients ≥ 10 years of age with relapsed and/or refractory Ph-like ALL (clinicaltrials.gov/NCT02115295).
Results: A total of 11 patients were enrolled (ruxolitinib cohort, n = 10; dasatinib cohort, n = 1) with a median age of 24 years. The median number of prior lines of treatment was 3. Genetic aberrations included CRLF2 overexpression (n = 8), HMBOX1-JAK2 fusion (n = 1), IGH-EPOR fusion (n = 1), and NUP214-ABL1 (n = 1). We observed no dose-limiting toxicities in the first 2 cohorts of patients receiving ruxolitinib (15 mg BID, n = 5 and 20 mg BID, n = 3), however enrollment of the third cohort (25 mg BID, n = 2) was terminated early due to slow accrual. The most common ≥ grade 3 adverse events were related to infectious complications. We observed overall low efficacy with 1/10 patients receiving ruxolitinib achieving complete remission with incomplete platelet count recovery.
Conclusion: Continued efforts should focus on identifying optimal treatment strategies for this high-risk group of patients.
期刊介绍:
Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed monthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma & Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.