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Efficacy of dasatinib in conjunction with α-interferon for the treatment of imatinib-resistant and dasatinib-resistant Ph+ acute lymphoblastic leukemia

Leukemia volume 23, pages 1687–1688 (2009)Cite this article

Despite notable progresses in the past few years, and, in particular, the advent of first- and second-generation tyrosine kinase inhibitors (TKI), the treatment of adult BCR-ABL1+ acute lymphoblastic leukemia (ALL) patients still remains an unsolved problem.1 In fact, though chemotherapy (CHT) and TKI are effective for inducing complete remission (CR), durable responses and possibly cure seem be achievable, at present, with stem cell transplantation only.2 We describe a unique case of BCR-ABL1+ ALL, relapsed after CHT, autologous stem cell transplantation (ASCT), imatinib and dasatinib courses, successfully treated with a combination of dasatinib and α-interferon (α-IFN).

In June 2007, the patient experienced a fourth relapse. Thus, the imatinib/α-IFN therapy was suspended and dasatinib (formerly BMS 354825; Bristol-Mayer-Squibb, New York, NY, USA), a second generation oral, dual inhibitor of BCR-ABL and SRC family kinases was given at the dose of 70 mg b.i.d., basing on its documented efficacy in imatinib-resistant cases.7 However, after obtaining a brief hematological CR with only mild decrease of the BCR-ABL1 transcript, the patient suffered from a fifth documented relapse in November 2007. Relevantly, no BCR-ABL1 point mutations assessed by conventional sequencing were documented at this time. Bearing in mind the previous efficacy of α-IFN combined with imatinib, after a short cytoreductive therapy consisting of four doses of vincristine (2 mg, days 1, 8, 15, 22) associated with 6-methylprednisolone (40 mg/day for 28 days), the patient received dasatinib (100 mg/day) plus α-IFN (0.5 MU, three times a week) from January 2008. We decided to administer to the patient α-IFN 0.5 MU, three times a week instead of 1 MU three times a week due to the heavily pretreated status of the patient and due to the higher potency of dasatinib with respect to imatinib. The combined treatment was indeed well tolerated, with only minor side effects (grade I–II skin rash), and dose reduction was not required at any time for any of the two drugs. Focusing on hematological toxicity, the patient did not present any grade IV toxicity. A transient grade III anemia was observed from the third month of the combined therapy. We did not observe any leucopenia or thrombocytopenia of any grade at any point during the combined treatment. Furthermore, most importantly, the treatment was quite effective by inducing, in particular, a dramatic reduction of the BCR-ABL1 transcripts, and the patient achieved a second molecular CR. At the time of writing, 13 months after receiving the first dose of the combination dasatinib/α-IFN, the patient is alive and in continuous second molecular CR (nested RT–PCR performed on bone marrow).

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Acknowledgements

Supported in part by AIL Pesaro Onlus.

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Author notes

  1. G Visani and A Isidori: These authors contributed equally to this article.

Authors and Affiliations

  1. Hematology and Hematopoietic Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy

    G Visani & A Isidori

  2. Department of Hematology and Medical Oncology ‘L. and A. Seràgnoli’, Molecular Pathology Laboratory, Unit of Hematopathology, University of Bologna, Bologna, Italy

    P Piccaluga

  3. Unit of Blood Diseases and Cell Therapies, University of Brescia, Brescia, ItalyE-mail: pesarohematology@yahoo.it,

    M Malagola

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  1. G Visani
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  2. P Piccaluga
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Visani, G., Piccaluga, P., Malagola, M. et al. Efficacy of dasatinib in conjunction with α-interferon for the treatment of imatinib-resistant and dasatinib-resistant Ph+ acute lymphoblastic leukemia. Leukemia 23, 1687–1688 (2009). https://doi.org/10.1038/leu.2009.96

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