Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients

Abstract

Most patients with diffuse large B-cell lymphoma (DLBCL) are diagnosed at age 60 or over. Challenges to effective therapy among older individuals include unfavorable biologic features of DLBCL, geriatric vulnerabilities, suboptimal treatment selection, and toxicities of cytotoxic chemotherapy. Wider application of geriatric assessments may help identify fit older patients who benefit from standard immunochemotherapy without unnecessary dose reductions. Conversely, attenuated regimens may provide a better balance of risk and benefit for selected unfit or frail patients. Supportive care with the use of corticosteroidbased prephase, prophylactic growth factors, and early institution of supportive/palliative care can help maximize treatment tolerance. Several novel or emerging therapies have demonstrated favorable toxicity profiles, thus facilitating effective treatment for elderly patients. In the relapsed or refractory setting, patients who are not candidates for stem cell transplantation can benefit from newly approved options including polatuzumab vedotin-based combinations or tafasitamab plus lenalidomide, which may have higher efficacy and/or lower toxicity than historical chemotherapy regimens. Chimeric antigen receptor T-cell therapy has been successfully applied to older patients outside of clinical trials. In the first-line setting, emerging immunotherapy options (bispecific antibodies) and targeted therapies (anti-CD20 antibodies combined with lenalidomide and/or B-cell receptor inhibitors) may provide chemotherapy-free approaches for DLBCL. Enrolling older patients in clinical trials will be paramount to fully examine potential efficacy and toxicity of these strategies. In this review, we discuss recent advances in fitness stratification and therapy that have expanded curative options for older patients, as well as future opportunities to improve outcomes in this population. The Oncologist 2020;9999:• • Implications for Practice: Management of diffuse large B-cell lymphoma in older patients poses challenges due to aggressive disease biology and geriatric vulnerability. While RCHOP remains standard first-line treatment, geriatric assessment may help evaluate patient's fitness for immunochemotherapy. Corticosteroid prephase, prophylactic growth factors, and early palliative care can improve tolerance of treatment. Novel salvage options (polatuzumab vedotin-based combinations, tafasitamab plus lenalidomide) or CAR T-cell therapy should be considered in the relapsed/refractory setting for patients ineligible for stem cell transplantation. Emerging immunotherapies (bispecific antibodies) and targeted therapies provide potential first-line chemotherapy-free approaches which need to be rigorously assessed in clinical trials that involve geriatric patients.

Multidisciplinary Approach to Older Adults with Hematologic Malignancies—a Paradigm Shift

“…An increasing rate of population aging worldwide [39] paired with median age of onset for most hematologic malignancies in the seventh decade [40] will lead to significant growth in the number of older patients with hematologic malignancies who will require specialized care. It is increasingly well recognized that older adults with hematologic malignancies require a different approach than younger patients [41,42]. Guidance is available for treatment recommendations based on "fitness" or "candidacy for intensive treatment" though these terms are often not well defined [42,43].…”

“…It is increasingly well recognized that older adults with hematologic malignancies require a different approach than younger patients [41,42]. Guidance is available for treatment recommendations based on "fitness" or "candidacy for intensive treatment" though these terms are often not well defined [42,43].…”

Whole-Body MRI Is an Effective Imaging Modality for Hematological Malignancy Treatment Response Assessment: A Systematic Review and Meta-Analysis

“…Three studies evaluated the diagnostic value of WB-MRI in children or young adults, while 10 studies focused on adult patients. In one study, the age of patients was not reported, and we assumed most patients to be adult since 86% (12/14) of patients were diagnosed with diffuse large B-cell lymphoma, a type of non-Hodgkin lymphoma commonly diagnosed at age over 60 (26). Five studies obtained WB-MRI with a magnetic field of 3.0 Tesla, and the remaining 9 used 1.5 Tesla.…”

Identification of Aging-Related Genes Associated with Prognostic Value and Immune Microenvironment Characteristics in Diffuse Large B-Cell Lymphoma

“…The median age at the time of diagnosis is 66 years; furthermore, 20.1% of patients are diagnosed between 75 and 84 years of age, 25.0% between 65 and 74 years of age, and 21.2% between 55 and 64 years of age. At present, effective treatment among the elderly remains challenging owing to the adverse invasive biological characteristics of DLBCL, the baseline health status of this patient population, the late toxicity of chemotherapy, and the poor therapeutic effect of the current treatment scheme on elderly patients [8,9]. Therefore, interest in the understanding of the molecular and genetic pathways dysregulated in ageing and DLBCL has tremendously increased, along with the interest in biomarkers as a quick and quantitative measure in all areas of biomedical research.…”