Pralatrexate Induces Responses in Patients with Highly Refractory Peripheral T-Cell Lymphoma (PTCL).
Bibliographic record
Abstract
Abstract Abstract 1678 Poster Board I-704 Background The outcome of patients with PTCL is poor and the majority of patients ultimately have refractory disease to a variety of agents, including standard therapy with CHOP or CHOP-like regimens. Pralatrexate is a rationally designed antifolate that has a high affinity for the reduced folate carrier-1 (RFC-1) and is likely to be retained longer within cancer cells due to efficient polyglutamation by folylpolyglutamyl synthetase. Phase 1 and 2 clinical trials have shown that pralatrexate is safe and active in hematologic malignancies including relapsed or refractory PTCL (O'Connor OA, JCO 2009:10.1200/JCO.2008.20.8470). The PROPEL study, a pivotal, international, Phase 2 single-arm trial, evaluated pralatrexate in patients with relapsed or refractory PTCL who had a median of 3 prior therapies. Pralatrexate treatment was well tolerated and showed an overall response rate of 28% (30/109 patients) by central independent review. The objective of this current analysis was to characterize the treatment response among patients who were considered to have refractory disease, defined as showing 1) no evidence of response to their most recent prior therapy or 2) no evidence of response to all prior therapies. Methods Patients received pralatrexate 30 mg/m2 once weekly for 6 weeks in 7-week cycles, with vitamin B12 and folic acid supplementation. Response to pralatrexate was assessed after each odd-numbered treatment cycle and was based on rigorous centralized review of imaging and clinical data using the International Workshop Criteria (Cheson BD, JCO 1999;17:1244). Results The most commonly used prior therapies were CHOP-based chemotherapy (70%), platinum-based multi-agent chemotherapy (41%), and non-platinum containing combination chemotherapy (39%). Eighteen (16%) patients received autologous stem-cell transplantation (SCT) prior to the PROPEL study. Of the 109 patients who were evaluable for response, 69 (63%) patients had no evidence of response to the most recent therapy and 26 (25%) patients had had no evidence of response to any therapy. The ORR for the 69 patients with no evidence of response to their most recent prior therapy was 25% (n=17) according to central review and 36% (n=25) according to investigator review. The median duration of response was 99 days (range, 41-535) by central review. The median number of prior systemic therapies for these 69 patients was 3 (range, 1-11). Twenty-six patients had no evidence of response to any prior therapy before initiating pralatrexate, having received a median of 2.5 prior therapies (range, 1-7). Five (19%) of these patients responded to pralatrexate by central review and 7 (27%) responded by investigator review. The duration of centrally reviewed response to pralatrexate in the patients with no evidence of response to any prior therapy was 54, 57, 69, 78, and 306 days. Conclusions Pralatrexate has demonstrated activity in patients with PTCL who were refractory to their most recent therapy, including patients who were refractory to all prior therapies. Responses to pralatrexate were observed in patients with disease that was refractory to a range of therapies used in PTCL, including SCT and a variety of single agent and combination chemotherapy regimens, suggesting that pralatrexate can overcome mechanisms of drug resistance in this population. Disclosures Savage: Allos Therapeutics, Inc.: Consultancy, Honoraria. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Pro:Allos Therapeutics, Inc.: Research Funding. Fruchtman:Allos Therapeutics, Inc.: Employment.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".