Bankstown Hospital - Grand Rounds - Further Reading

Lymphoma in the elderly

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Allen, P. (2020). "Diffuse Large B-Cell Lymphoma in the Elderly: Current Approaches." Current Oncology Reports 22(11): 114  https://doi.org/10.1007/s11912-020-00976-x

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            Older patients with diffuse large B-cell lymphoma (DLBCL) may face challenges in treatment due to comorbidities and tolerance of chemotherapy.

Arcari, A., et al. (2023). "New treatment options in elderly patients with Diffuse Large B-cell Lymphoma." Front Oncol 13: 1214026   2234-943x

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            Most patients with Diffuse Large B-cell Lymphoma (DLBCL) are old (>65 years of age) and this population is expected to increase in the following years. A simplified geriatric assessment based on a careful evaluation of the fitness status and comorbidities is essential to choose the correct intensity of treatment. Fit older patients can benefit from a standard immunochemotherapy, while unfit/frail patients frequently need reduced doses or substitution of particular agents with less toxic ones. This review focuses on new therapies (e.g., polatuzumab vedotin, tafasitamab, bispecific antibodies) that have indicated promising results in relapsed/refractory patients, particularly in cases not eligible to transplant. Some of these new drugs have been tested as single agents or in combinations as first-line treatment, aiming to improve the outcome of the traditional chemotherapy. If preliminary efficacy and safety data are confirmed in future clinical trials, a chemo-free immunotherapic approach could become an alternative option to offer a curative treatment even in frail patients.

Liu, Y., et al. (2021). "Diagnosis, prognosis and treatment of primary central nervous system lymphoma in the elderly population (Review)." Int J Oncol 58(3): 371-387  https://doi.org/10.3892/ijo.2021.5180  REQUEST THIS ARTICLE

            Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non‑Hodgkin lymphoma that is unique and different from systemic diffuse large B‑cell lymphomas. The median age at diagnosis of PCNSL is 65 years and its incidence is rising rapidly in the elderly population. A total of ≥20% of all patients with PCNSL are ≥80 years old. Notably, age has been identified as an independent poor prognostic factor for PCNSL. Elderly patients have an inferior prognosis to that of younger patients and are more severely affected by iatrogenic toxicity; therefore, elderly patients represent a unique and vulnerable treatment subgroup. The present review summarized the available literature to provide an improved understanding of the epidemiology, clinical characteristics, diagnosis, prognosis and management of PCNSL in the elderly population. Notably, the incidence of PCNSL in immunocompetent elderly patients, predominantly in men, is increasing. For the diagnosis of CNSL, imaging‑guided stereotactic biopsy is considered the gold standard. When stereotactic biopsy is not possible or conclusive, certain biomarkers have been described that can help establish a diagnosis. PCNSL has a very poor prognosis in the elderly, even though several prognostic scoring systems exist and several prognostic markers have been reported in patients with PCNSL. Furthermore, the treatment of elderly patients remains challenging; it is unlikely that a novel agent could be used as a curative monotherapy; however, a combination of novel agents with polychemotherapy or its combination with other novel drugs may have therapeutic potential.

Tavares, A. and I. Moreira (2021). "Diffuse large B-cell lymphoma in very elderly patients: Towards best tailored treatment – A systematic review." Critical Reviews in Oncology/Hematology 160: 103294  REQUEST THIS ARTICLE

https://www.sciencedirect.com/science/article/pii/S1040842821000822

            Introduction Diffuse large B cell Lymphoma (DLBCL) is a potentially curative lymphoma with increasing incidence with ageing. Treatment of elderly DLBCL patients represents a particular challenge due to their comorbidities and performance status. Methods A search for original articles focused on the treatment of elderly DLBCL patients was performed in PubMed database and 633 were found and reviewed. Thirty-eight studies meeting our inclusion criteria were published since 2007. Results Thirteen studies were retrospective and 25 phase II/III clinical trials. Most of them investigated the efficacy of dose-adjusted R−CHOP regimen. Alternative therapeutic drugs together with geriatric assessment were also evaluated. For fit patients aged 80 and over, the strongest evidence favours R-miniCHOP regimen. Conclusion A dose-adjusted R−CHOP may be the recommended treatment in elderly DLBCL patients. New tools such as the Comprehensive Geriatric Assessment provide useful guidance for treatment choice, based on comorbidities and frailty index of this group.

Wästerlid, T., et al. (2022). "Diffuse large B-cell lymphoma among the elderly: a narrative review of current knowledge and future perspectives." Annals of Lymphoma 6  https://aol.amegroups.org/article/view/8334 REQUEST THIS ARTICLE

Background and Objective: Management of very elderly or frail patients with diffuse large B-cell lymphoma (DLBCL) is a major clinical challenge. Comprehensive data on disease biology, treatment options, frailty assessment, and prognostic estimation in this group are limited. In this narrative review, we seek to provide an overview of the epidemiology of DLBCL and prognostic factors. We review methods for frailty assessments, first line treatment options including alternatives to R-CHOP, management of relapsed/refractory DLBCL, and the potential of novel therapies for elderly patients with DLBCL.

Methods: Relevant studies were identified using the PubMed database. No filters were used to specify text language or publication dates.

Key Content and Findings: Available data suggest that elderly patients who can tolerate standard frontline therapies for DLBCL with regimens such as R-CHOP experience outcomes similar to those of younger patients. This underscores the importance of individual frailty assessment to identify candidates for standard treatment and those who are better managed with reduced, adapted, or completely different treatment protocols. For patients with relapsed/refractory disease there is no standard, but chimeric antigen receptor T (CAR-T) cell therapy, polatuzumab with bendamustine and rituximab, and lenalidomide alone or in combination all represent viable options. Novel therapies under investigation, used in combination with standard therapies, as lead-in or maintenance therapy, or as stand-alone treatments, may help to improve treatment outcomes and reduce toxicity in this population.

Conclusions: Given the lack of studies focusing exclusively on the elderly population, we recommend full dose R-CHOP to fit elderly patients below age 80 years. For patients 80 years or older, or with comorbidities, alternatives include R-miniCHOP or CEOP. Treatment in the relapsed/refractory setting is challenging, but novel therapies provide opportunities to improve outcomes.