Page 136 - Haematologica May 2022

Ferrata Storti Foundation
Haematologica 2022 Volume 107(5):1144-1152
Prephase rituximab/prednisone therapy and aging-related, proinflammatory cytokine milieu in older, vulnerable patients with newly diagnosed diffuse large B-cell lymphoma
Richard J. Lin,1,2* Colette N. Owens,1,2* Esther Drill,3 Augustine Iannotta,1 Mayan Oliveros,1 Dylan L. Schick,1 Ariela Noy,1,2 John F. Gerecitano,1,2 Pamela R. Drullinsky,1,2 Philip C. Caron,1,2 Anita Kumar,1,2
Matthew J. Matasar,1,2 Craig Moskowitz,1,2 Beatriz Korc-Grodzicki,2,4 Andrew D. Zelenetz,1,2 Gilles A. Salles,1,2 and Paul A. Hamlin1,2
1Department of Medicine, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center; 2Department of Medicine, Weill Cornell Medical College; 3Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center and 4Department of Medicine, Geriatrics Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
*RJL and CNO contributed equally as co-first authors.
ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) predominantly affects older adults with suboptimal therapeutic outcomes due to increased treatment-related mortality and toxicities in vulnerable patients, clinically defined by geriatric impairments such as functional limitation, multimorbidity, or cognitive deficits. In this prospective pilot study, we evaluated a rituximab/prednisone prephase treatment strategy in 33 older, vulnerable patients with newly diagnosed DLBCL, defined by either age ≥70 years or age 60-70 years with Karnofsky performance scale (KPS) <80. A single dose of rituximab 375 mg/m2 between 3-10 days and oral pred- nisone for at least 5 days prior to the first dose of chemoimmunotherapy was administered. All patients completed prephase treatment and all but one commenced anthracycline-based chemoimmunotherapy. Only one early cycle death occurred. Toxicity events, defined by either unplanned hospitalization, unplanned dose reduction/delay, or chemotherapy dis- continuation, occurred in 22 patients (67%). Sixteen patients (48%) expe- rienced grade 3 or higher non-hematologic toxicities and/or grade 4 or higher hematologic toxicities. With a median follow-up of 4.4 years, both 5-year progression-free survival and overall survival were at 81% (95% confidence interval: 69-96). Importantly, we found that phenotypic impairments in basic and instrumental activities of daily living, physical function, mobility, KPS, and Cancer and Aging Research Group chemotherapy toxicity risk score were significantly associated with senescence-associated, proinflammatory cytokine milieu which was read- ily reversed with prephase treatment, potentially explaining its clinical effectiveness. Prephase therapy with rituximab/prednisone should be considered for all older, vulnerable DLBCL patients prior to curative intent, anthracycline-based chemoimmunotherapy. This trial was regis- tered as clinicaltrials gov. Identifier: NCT 89028394.
Introduction
Diffuse large B-cell lymphoma (DLBCL) disproportionally affects older patients and improving their therapeutic outcomes remains an unmet medical need. Epidemiologic studies have shown that even in the rituximab era, many older patients either do not receive or receive suboptimal dose and/or duration of chemoimmunotherapy to achieve a curative intent.1,2 While the biology of disease may be more aggressive,3 older patients commonly have multimorbidity, functional and/or cognitive impairment, or overt frailty that limits the delivery of upfront, cur-
Non-Hodgkin Lymphoma
Correspondence:
PAUL A. HAMLIN
hamlinp@mskcc.org
Received: March 6, 2021. Accepted: July 12, 2021. Pre-published: July 22, 2021.
https://doi.org/10.3324/haematol.2021.278719 ©2022 Ferrata Storti Foundation
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