Correspondence

Panniculitis during Dasatinib Therapy for Imatinib-Resistant Chronic Myelogenous Leukemia

N Engl J Med 2006; 354:2623-2624June 15, 2006

Article

To the Editor:

We describe two cases of panniculitis apparently caused by dasatinib. In one, management after the diagnosis of the panniculitis allowed dasatinib therapy to be continued.

In the first case, a 55-year-old woman (Patient 1) presented in the chronic phase of chronic myelogenous leukemia (CML) and did not have a major cytogenetic response (defined by the presence of the Philadelphia chromosome in <35 percent of cells in metaphase) to imatinib mesylate at a dose of 800 mg daily. She was known to have the activation-loop mutation H396R, which is associated with resistance to imatinib.1 She entered a phase 2 trial of dasatinib (BMS-354825, Bristol-Myers Squibb), a new inhibitor of the BCR-ABL tyrosine kinase, at a dose of 70 mg orally twice daily.

During the fourth week of treatment, symptoms — fever (temperature, 38.1°C) and painful subcutaneous nodules with overlying erythema on her thighs — developed. Dasatinib was withheld, and within a week the rash resolved. When dasatinib was restarted, the fever and rash recurred, this time on the arms, legs, and vulva. Biopsy of a skin lesion revealed lobular panniculitis, with massive infiltration by polymorphonuclear leukocytes (Figure 1Figure 1Panniculitis in Patient 1 Demonstrated by Infiltration of the Hypodermis by Polymorphonuclear Leukocytes, at Low (Panel A) and High (Panel B) Magnifications.). Dasatinib was withheld again. After resolution of the second episode, dasatinib was reintroduced together with 50 mg of prednisone per day; no recurrence of panniculitis was noted, even when the dose of dasatinib was increased to 70 mg twice daily. Prednisone was tapered after two weeks; because rash and fever recurred when the dose of prednisone was decreased below 5 mg per day, however, the patient continued to receive prednisone at this dose. Twelve weeks after the start of treatment, the patient had a complete cytogenetic response, and at six months, a polymerase-chain-reaction assay of peripheral blood for the BCR-ABL fusion gene was negative (as reflected by a decrease of >4.5 log copies as compared with values at the start of treatment).

In the second case, a 67-year-old woman (Patient 2) with chronic-phase CML who did not have a major cytogenetic response to imatinib was treated with 70 mg of dasatinib orally twice daily. Three months later, a rash similar to that occurring in Patient 1 developed but resolved only when dasatinib was stopped. A skin biopsy confirmed the diagnosis of panniculitis. In Patient 2, the rash recurred when dasatinib was restarted and was not sensitive to steroid treatment.

Since both patients tolerated imatinib without any cutaneous side effects, the toxic effects encountered with dasatinib therapy might have been caused by the inhibition of a tyrosine kinase that was affected by dasatinib but not imatinib. Another possibility is that dasatinib caused panniculitis through the more complete inhibition of a common target, such as ABL or platelet-derived growth factor receptor β.

Sarit Assouline, M.D.
Jewish General Hospital, Montreal, QC H3T 1E2, Canada

Pierre Laneuville, M.D.
Royal Victoria Hospital, Montreal, QC H3A 1A1, Canada

Carlo Gambacorti-Passerini, M.D.
McGill University, Montreal, QC H3T 1E2, Canada
carlo.gambacorti-passerini@mcgill.ca

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Citing Articles (12)

Citing Articles

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   IRIS AMITAY-LAISH, SALOMON M. STEMMER, MARIO E. LACOUTURE. (2011) Adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib. Dermatologic Therapy 24:4, 386-395
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   A. de Masson, S. Bouvresse, T. Clérici, E. Mahé, P. Saïag. (2011) Panniculite neutrophilique récidivante chez une patiente traitée par imatinib mésilate puis dasatinib pour une leucémie myéloïde chronique. Annales de Dermatologie et de Vénéréologie 138:2, 135-139
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   S Mustjoki, M Ekblom, T P Arstila, I Dybedal, P K Epling-Burnette, F Guilhot, H Hjorth-Hansen, M Höglund, P Kovanen, T Laurinolli, J Liesveld, R Paquette, J Pinilla-Ibarz, A Rauhala, N Shah, B Simonsson, M Sinisalo, J L Steegmann, L Stenke, K Porkka. (2009) Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia 23:8, 1398-1405
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   Matthew J Taylor, Paul A Scuffham. (2009) Pharmacoeconomic benefits of dasatinib in the treatment of imatinib-resistant patients with chronic myelogenous leukemia. Expert Review of Pharmacoeconomics & Outcomes Research 9:2, 117-121
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    Lisa A. Hammond-Thelin. (2008) Cutaneous Reactions Related to Systemic Immunomodulators and Targeted Therapeutics. Dermatologic Clinics 26:1, 121-159
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