Background
Phase II, single-arm, pivotal study. 111 patients with R/R PTCL after ≥1 prior therapy. Pralatrexate is a folate analog metabolic inhibitor designed with higher affinity for reduced folate carrier-1 (RFC-1) than methotrexate. PROPEL was the pivotal study establishing pralatrexate as the first agent FDA-approved specifically for PTCL.
Interventions and follow up
Regimen: Pralatrexate 30 mg/m² IV once weekly × 6 of 7 weeks with vitamin B12/folate supplementation in R/R peripheral T-cell lymphoma
Primary endpoint: Overall response rate (independent review committee)
mFollow up: Not reported (median OS 14.5 months)
Primary endpoint: Overall response rate (independent review committee)
mFollow up: Not reported (median OS 14.5 months)
Results
ORR (primary): 29% (95% CI 21–39%)
CR rate: 11%
mDOR: 10.1 months
mOS: 14.5 months
CR rate: 11%
mDOR: 10.1 months
mOS: 14.5 months
Adverse events
Hematologic: Grade ≥3 thrombocytopenia 32%, grade ≥3 anemia 18%
Mucocutaneous/other: Grade ≥3 mucositis 22%, liver function test elevations 13%, peripheral edema 30% (any grade); treatment discontinuation due to AEs 23%
Mucocutaneous/other: Grade ≥3 mucositis 22%, liver function test elevations 13%, peripheral edema 30% (any grade); treatment discontinuation due to AEs 23%
Conclusions
Pralatrexate achieved a 29% ORR with a 10.1-month mDOR in heavily pretreated R/R PTCL — modest efficacy but durable responses in a subset — leading to FDA accelerated approval in 2009 as the first PTCL-specific drug.
Key Limitations
Single-arm Phase II without a randomized comparator, so efficacy versus other salvage options cannot be inferred. The 29% ORR and 11% CR rate are modest, and substantial mucocutaneous and hematologic toxicity (mucositis 22%, thrombocytopenia 32%) led to 23% discontinuation. The heterogeneous PTCL population limits subtype-specific conclusions. No OS comparator and a relatively small sample (n=111).
Clinical Context
PROPEL led to FDA accelerated approval of pralatrexate for R/R PTCL (September 2009) — the first agent approved specifically in this disease. Along with romidepsin, belinostat, and brentuximab vedotin (for CD30+ disease), pralatrexate is among the single agents available for R/R PTCL, where outcomes remain poor and allogeneic transplant is considered for eligible responders. ESMO recognizes these agents as options in the relapsed/refractory setting.