Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma

Author:

Horwitz Steven M.1,Kim Youn H.2,Foss Francine3,Zain Jasmine M.4,Myskowski Patricia L.1,Lechowicz Mary Jo5,Fisher David C.6,Shustov Andrei R.7,Bartlett Nancy L.8,Delioukina Maria L.9,Koutsoukos Tony10,Saunders Michael E.10,O'Connor Owen A.11,Duvic Madeleine12

Affiliation:

1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY;

2. Stanford Cancer Center, Stanford University, Stanford, CA;

3. Yale Medical Oncology, Yale Cancer Center, New Haven, CT;

4. Hematology/Oncology, New York University Langone Medical Center, New York, NY;

5. Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, GA;

6. Department of Medicine, Dana-Farber Cancer Institute, Boston, MA;

7. University of Washington School of Medicine, Seattle, WA;

8. Chair in Medical Oncology, Washington University School of Medicine, St Louis, MO;

9. Blood and Marrow Transplant Program, Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA;

10. Allos Therapeutics Inc, Princeton, NJ;

11. Hematology/Oncology, Irving Cancer Research Center, The New York Presbyterian Hospital–Columbia University Medical Center, New York, NY; and

12. Department of Dermatology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX

Abstract

Abstract Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after ≥ 1 prior systemic therapy. The starting dose and schedule was 30 mg/m2/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m2/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m2/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m2/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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