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Final Report Of a Phase II Clinical Trial Of Lenalidomide Monotherapy For T-Cell Lymphoma

2013· article· en· W2253747904 on OpenAlexaff
Ethan Toumishey, Angeli Prasad, Greg Dueck, Neil Chua, Daygen L. Finch, Douglas A. Stewart, Darrell White, Richard H. van der Jagt, James B. Johnston, Andrew R. Belch, Tony Reiman

Bibliographic record

VenueBlood · 2013
Typearticle
Languageen
FieldMedicine
TopicCutaneous lymphoproliferative disorders research
Canadian institutionsSaint John Regional HospitalCancerCare ManitobaUniversity of AlbertaQueen Elizabeth II Health Sciences CentreOttawa HospitalBC Cancer AgencyUniversity of CalgaryUniversity of New BrunswickDalhousie University
Fundersnot available
KeywordsMedicineLenalidomideInternal medicineGastroenterologyPeripheral T-cell lymphomaLymphomaAnaplastic large-cell lymphomaPhases of clinical researchT-cell lymphomaMycosis fungoidesClinical endpointTransplantationOncologyClinical trialSurgeryT cellMultiple myelomaImmunologyImmune system

Abstract

fetched live from OpenAlex

Abstract Background Patients with T-cell lymphomas face a poorer prognosis when compared to patients with B-cell lymphomas. New therapeutic approaches need to be developed in order to improve outcomes for these patients. We report the final results of a phase 2 multicenter clinical trial evaluating lenalidomide monotherapy in T-cell lymphomas. Methods Forty patients with relapsed and refractory T-cell lymphomas other than mycosis fungoides, as well as patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy, were prescribed oral lenalidomide (25mg daily) on days 1 to 21 of each 28 day cycle, with standardized dose reductions for toxicity. Treatment continued until disease progression, death or unacceptable toxicity. The primary endpoint was overall response rate, and secondary endpoints were complete and partial response rates, progression-free and overall survival (PFS, OS), and safety. We also determined duration of response (DoR). Results Forty patients were enrolled in the study; one was subsequently deemed ineligible. In the 39 eligible patients, the median age was 65. ECOG PS was 0-1 (n=29), 2 (n=8), and 3 (n=2). The histology of the studied cases included peripheral T-cell unspecified (PTCL-u, n=14), angioimmunoblastic (n=9), anaplastic large cell (n=10), enteropathic T-cell (n=2), Hepatosplenic gamma/delta (n=2), and lymphoblastic T-cell lymphoma (n=2). The number of prior therapies was 0 (n=8), 1 (n=14), 2 (n=8), 3 (n=6), 4 (n=2), and 5 (n=1). Five patients had previous autologous stem cell transplant. Eleven patients were refractory to their previous treatment. The median time from diagnosis until the start of treatment was 14 months (range, 1-204 months). The median time from completion of prior therapy to the start of lenalidomide was 5 months (range, 1-48 months). The ORR was 10/39 (26%); 3 (8%) were complete responses and 7 were partial responses. Responses occurred in anaplastic, angioimmunoblastic, and PTCL-u histologies. Three additional patients had SD ≥5 cycles. The median OS was 12 months (range<1-69+ months), median PFS was 4 months (range,<1-50+ months) and the median DoR was 13 months (range 2-37+ months), including 5 responses lasting greater than 1 year. The most common grade 4 adverse event was thrombocytopenia (21%) while pain NOS (21%) and neutropenia (13%) were the most commonly reported grade 3 adverse events. Among the patients who had relapsed/refractory peripheral T-cell lymphoma (n=29) the ORR was 24%, median OS was 12 months, median PFS was 4 months, and median DoR was 5 months (range, 2-37+ months). The ORR of the subpopulation of previously untreated patients who were not eligible for combined chemotherapy (n=8) was 43%, median OS was 22 months (range,<1-38+ months), median PFS was 2 months (range,<1-38+ months), and median DoR was 21 months (range 5-28+ months). Discussion In T-cell lymphomas, oral lenalidomide monotherapy demonstrated clinically relevant efficacy. The toxicity profile in T-cell lymphoma is manageable and consistent with prior studies involving lenalidomide. Lenalidomide also showed promise for patients who are not eligible for combination chemotherapy. The results with lenalidomide in relapsed/refractory patients are comparable to those seen with other available monotherapies for this disease. Several durable (>1 year) responses were seen, but the proportion of durable responses was low. Future development of lenalidomide therapy for T-cell lymphomas should include efforts to identify the subset of patients most likely to benefit, and the development of rational drug combinations. Disclosures: Off Label Use: Lenalidomide was prescribed to treat T-cell lymphoma. Stewart:Celgene: Honoraria. van der Jagt:Millenium: Consultancy; Roche: Consultancy; Celgene: Consultancy. Reiman:Celgene: Consultancy; Celgene: Research Funding.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.442
Threshold uncertainty score0.472

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.095
GPT teacher head0.420
Teacher spread0.325 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

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".

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Citations2
Published2013
Admission routes1
Has abstractyes

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