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Author Notes:

Gita Thanarajasingam, MD., Mayo Clinic, 200 First Street SW, Rochester, MN 55906. Phone: (507) 266-4800, Fax: (507) 266-4972. Email: thanarajasingam.gita@mayo.edu

Dr. Thanarajasingam and Dr. Dueck disclose research funding from the US National Institutes of Health (National Cancer Institute). Dr. Witzig reports non-financial support from Celgene provided to his institution, outside the submitted work. Dr. Habermann has served on the scientific advisory board of Celgene and of Kite Pharmaceuticals, for which he has received no renumeration. Dr. Flowers reports grants from V Foundation, grants from National Cancer Institute, during the conduct of the study; other from Spectrum, BeiGene, Celgene, Optum Rx, Seattle Genetics, GIlead, Bayer, Karyopharm, MEI Pharmaceuticals, other from Genentech/Biogen-Idec/Roche (unpaid), Millennium/Takeda(unpaid), from Research Funding:Abbvie, Acerta, Celgene, Gilead Sciences, Infinity Pharmaceuticals, Janssen Pharmaceutical, Millennium/Takeda, Spectrum, Onyx Pharmaceuticals, Phamacyclics, NIH, outside the submitted work. Dr. Leonard reports personal fees from Celgene, personal fees from Gilead/Kite, personal fees from Teva, personal fees from ADC Therapeutics, personal fees from Abbvie, personal fees from Genmab, personal fees from Biotest, personal fees from Regeneron, personal fees from Roche/Genentech, personal fees from Sutro, personal fees from Sunesis, personal fees from BMS, personal fees from Epizyme, personal fees from Pfizer, personal fees from Bayer, personal fees from United Therapeutics, personal fees from MEI Pharma, personal fees from Novartis, personal fees from Merck, personal fees from Morphosys, personal fees from Beigene, personal fees from AstraZeneca, personal fees from Nordic Nanovector, personal fees from Karyopharm, personal fees from Sandoz, personal fees from Miltenyi, outside the submitted work.

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Research Funding:

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821, U10CA180882, and UG1CA189823 (to the Alliance for Clinical Trials in Oncology), U10CA180790, UG1CA233339, Mayo Clinic Center for Clinical and Translational Science, KL2 Mentored Career Development Award, Funded by National Center for Advancing Translational Sciences (KL2 TR002379), Mayo Clinic Lymphoma SPORE (P50 CA97274–14) Career Development Award, and the Lymphoma Research Foundation Mentoring Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Lymphoma Research Foundation. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • PATIENT-REPORTED OUTCOMES
  • QUALITY-OF-LIFE
  • CLINICAL-TRIALS
  • END-POINTS
  • IMPROVE

Longitudinal Toxicity over Time (ToxT) analysis to evaluate tolerability: a case study of lenalidomide in the CALGB 50401 (Alliance) trial

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Journal Title:

LANCET HAEMATOLOGY

Volume:

Volume 7, Number 6

Publisher:

, Pages E490-E497

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease. Modern approaches to the evaluation and reporting of toxicity that capture the tolerability of treatment to the patient are imperative. In this Viewpoint, we present a focused, pilot, and longitudinal Toxicity over Time analysis of adverse events from lenalidomide and lenalidomide with rituximab in patients with follicular lymphoma treated in the CALGB 50401 (Alliance; NCT00238238) trial to define the trajectory of adverse events and quantify the burden of continuous, low-grade events. Toxicity over Time analyses provided clinically relevant descriptions of neutropenia and fatigue trajectories caused by lenalidomide that were not identified by standard analysis of the maximum grade events defined by the Common Terminology Criteria for Adverse Events. Systematic, rigorous incorporation of patient-reported outcomes in clinical trials will be crucial to our understanding of the tolerability of chronically administered therapies in patients with haematological malignancies.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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