Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL)
Menée sur 54 patients atteints d'un lymphome cutané à cellules T réfractaire ou récidivant, cette étude évalue l'efficacité et la toxicité de diverses doses de pralatrexate
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/week intravenously for 3/4 weeks. Subsequent starting doses were 20, 15, 10 mg/m2/week for 3/4 or 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/week for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. Most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m2/week for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.