Frailty in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Receiving Curative-Intent Therapy: A Population-Based Study

Authors: Abi Vijenthira MD, SM1,2, Lee Mozessohn MD, MPH2,3,4, Chenthila Nagamuthu MPH4, Ning Liu PhD4, Danielle Blunt MD5, Shabbir Alibhai MD, PhD2,6, Anca Prica MD, MSc1,2, and Matthew C. Cheung MD, SM2,3,4
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  • 1 Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre,
  • | 2 Department of Medicine, University of Toronto,
  • | 3 Division of Medical Oncology and Hematology, Sunnybrook Odette Cancer Centre, and
  • | 4 Cancer Research Program, Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada;
  • | 5 Division of Hematology, Royal Adelaide Hospital, Adelaide, South Australia, Australia; and
  • | 6 Division of General Internal Medicine and Geriatrics, University Health Network, Toronto, Ontario, Canada.

Background: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment. Methods: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality. Results: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70–80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6–2.0; P<.0001). Frail patients had higher healthcare utilization during treatment, with most hospitalizations related to infection and/or lymphoma. In multivariable modeling controlling for age, inpatient diagnosis, number of chemoimmunotherapy cycles received, comorbidity burden, and healthcare utilization, frailty remained independently associated with 1-year mortality (adjusted hazard ratio, 1.5; 95% CI, 1.3–1.7; P<.0001). Conclusions: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.

Submitted December 8, 2021; final revision received March 22, 2022; accepted for publication March 23, 2022.

Author contributions: Conceptualization: Vijenthira, Mozessohn, Alibhai, Prica, Cheung. Data curation: Nagamuthu, Liu. Formal analysis: Nagamuthu, Liu, Blunt. Funding acquisition: Vijenthira, Prica, Cheung. Methodology: All authors. Project administration: Cheung. Software: Nagamuthu, Liu. Supervision: Alibhai, Prica, Cheung. Writing—original draft: Vijenthira. Writing—review and editing: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization regarding the preparation, analysis, results, or discussion of this article.

Funding: This study was supported by funding from the Conquer Cancer Foundation of the ASCO Young Investigator Award, the Lymphoma Clinical Research Mentoring Program, the Hold ’Em for Life Oncology Clinician Scientist Award, and the Ontario Ministry of Health and Long Term Care Clinician Investigator Program.

Correspondence: Matthew C. Cheung, MD, SM, Sunnybrook Health Sciences Centre, Room T2 044, 2075 Bayview Avenue, Toronto ON M4N 3M5, Canada. Email: matthew.cheung@sunnybrook.ca

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