Pralatrexate Reverses the Trend to Progressive Resistance to Successive Systemic Treatment Regimens In Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)
Bibliographic record
Abstract
Abstract Abstract 4881 Background: In a wide range of malignancies, including nonHodgkin lymphoma (NHL), treatment-naive patients generally show a greater response to chemotherapy than patients receiving second-line or subsequent therapy. Furthermore, objective response rate (ORR) and progression-free survival (PFS) generally decrease with each subsequent line of therapy, the hallmark of acquired drug resistance. This trend would also be expected for PTCL, although there are no published studies or retrospective data analyses specifically in PTCL describing the pattern of response to successive treatments. The goal of the analysis presented here was to determine whether a trend of progressive resistance is observed in relapsed or refractory PTCL, and to identify the efficacy (PFS and ORR) of pralatrexate (FOLOTYN®) as a subsequent therapy relative to previous treatments. The PROPEL (Pralatrexate in Patients with Relapsed Or Refractory Peripheral T-cell Lymphoma) study is the largest data set published for relapsed or refractory PTCL to date. As a part of the patients' medical history, data were collected on response and PFS in previous lines of therapy. Patients had a median of 3 prior systemic therapies (range 1 to 12). Overall in the PROPEL study, pralatrexate demonstrated a 39% ORR by investigator assessment and a 29% ORR by central review. The median duration of response was 8.1 months by investigator assessment and 10.1 months by central review. The median duration of PFS was 4.0 months by investigator assessment and 3.5 months by central review. Median overall survival was 14.5 months. Methods: Analyses were conducted on patients according to the number of prior systemic therapies. PFS and ORR of the third therapy prior to pralatrexate (-3) were compared with those of the second prior therapy (-2); PFS and ORR of second prior therapy (-2) were compared with those of the last (most recent) line of therapy (-1) prior to pralatrexate; and PFS and ORR of last line of therapy (-1) were compared with pralatrexate therapy for these patients. These analyses utilized investigator assessment of PFS and response since review of tumor assessments on prior therapies was based on investigator assessment. Results: 57 patients had undergone at least 3 prior systemic therapies before entry into PROPEL. Of these 57 patients, 34 had > 3 previous treatments and 23 had exactly 3 previous treatments. As presented in the table below, a trend of reduced PFS and ORR with successive lines of therapy was observed. The hazard ratio (HR) for outcomes worsens with successive lines of therapy [-3 vs -2: HR 0.660 (0.450, 0.967); -2 vs -1: HR 0.823 (0.566, 1.195)]. Thus, patients with ≥3 prior lines of therapy (-3) had higher response rates and PFS vs the RR and PFS in the same patients with later lines of therapy (-2 or -1). According to this analysis, this trend was reversed with pralatrexate treatment demonstrated by a higher response rate (40%) and longer PFS (median =134 days) than the previous line of therapy. The only HR >1 in this analysis, indicating a longer PFS for a more recent line of therapy vs the most recent prior line of therapy, is for pralatrexate vs -1. The same analyses were performed on the 86 patients who had undergone at least 2 previous treatments. The trend for PFS and response rate to decrease with each subsequent treatment was again demonstrated and was again reversed with pralatrexate (HR for PFS = 1.201 [-1 vs -0] vs 0.785 [-2 vs -1]). Conclusions: This is the first analysis to demonstrate that patients with PTCL exhibit the same pattern of progressive resistance as seen in most other tumor types. It is also the first to demonstrate that a drug, pralatrexate, can reverse the pattern of progressive resistance in patients with drug-resistant PTCL. Pralatrexate demonstrated higher responses and longer PFS than would be expected in a later line of therapy setting, thus reversing the trend of progressive resistance. Disclosures: O'Connor: Allos Therapeutics, Inc.: Research Funding. Haouin: GlaxoSmithKline: Consultancy; Amgen Inc.: Consultancy. Gisselbrecht: Allos Therapeutics, Inc.: Research Funding. Foss: Allos Therapeutics, Inc.: Consultancy, Speaker. Savage: Allos Therapeutics, Inc.: Consultancy, Honoraria. Pro: Allos Therapeutics, Inc.: Research Funding. Pinter-Brown: Allos Therapeutics, Inc.: Consultancy. Horwitz: Allos Therapeutics, Inc.: Consultancy, Research Funding. Jacobsen: Allos Therapeutics, Inc.: Consultancy. Koutsoukos: Allos Therapeutics, Inc.: Employment. Fruchtman: Allos Therapeutics, Inc.: Employment.
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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".