A Phase I/II Trial of Ruxolitinib with Chemotherapy for Patients with Relapsed and/or Refractory Philadelphia-like Acute Lymphoblastic Leukemia.

IF 2.7 4区 医学 Q2 HEMATOLOGY
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.

Ruxolitinib联合化疗治疗复发和/或难治性费城样急性淋巴细胞白血病的I/II期临床试验
背景:费城染色体样急性淋巴细胞白血病(ALL)是B-ALL的高危亚型。该疾病是由一系列激酶激活突变驱动的,导致与ph阳性ALL相似的基因表达谱,并且可能通过JAK或abl定向激酶抑制来靶向。患者和方法:我们进行了一项I/II期试验,以探讨鲁索利替尼或达沙替尼联合Hyper-CVAD化疗治疗≥10岁复发和/或难治性ph样ALL患者的安全性和有效性(clinicaltrials.gov/NCT02115295).Results:共入组11例患者(鲁索利替尼队列,n = 10;达沙替尼队列,n = 1),中位年龄24岁。先前治疗的中位数为3条。遗传畸变包括CRLF2过表达(n = 8)、HMBOX1-JAK2融合(n = 1)、IGH-EPOR融合(n = 1)和NUP214-ABL1 (n = 1)。我们观察到在接受ruxolitinib治疗的患者的前两个队列(15mg BID, n = 5和20mg BID, n = 3)中没有剂量限制性毒性,然而第三个队列(25mg BID, n = 2)的入组由于累积缓慢而提前终止。最常见的≥3级不良事件与感染并发症有关。我们观察到总体低疗效,1/10接受ruxolitinib的患者完全缓解,血小板计数恢复不完全。结论:应继续努力确定这一高危人群的最佳治疗策略。
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来源期刊
CiteScore
2.70
自引率
3.70%
发文量
1606
审稿时长
26 days
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.
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