Oncology

Chronic Lymphocytic Leukemia

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Treating Chronic Lymphocytic Leukemia in Patients Aged 80 Years and Older

patient care perspectives by John C. Byrd, MD

Overview

Older patients with chronic lymphocytic leukemia (CLL) have more options for well-tolerated treatment than in the past. Planning treatment involves choosing the most effective therapy in light of their comorbidities.

Expert Commentary

John C. Byrd, MD

The Gordon and Helen Hughes Taylor Professor and Chair
Department of Internal Medicine
University of Cincinnati College of Medicine
Cincinnati, OH

“One really needs to be in touch with the other things that are occurring in addition to the CLL in this patient group, and you have to scale the therapeutic intensity to match what you are treating. Treatment might be different for an 80-year-old patient vs a 95-year-old patient.”

John C. Byrd, MD

The risk of dying from CLL is greater in patients aged 80 years and older than it is in younger patients. This has been seen repeatedly in clinical trials and epidemiology data, and it stems from reasons that include a lower tolerance for treatment-related toxicities, immunosenescence and higher levels of inflammation, and more comorbidities. 

Treatment options for older patients with CLL have changed fundamentally during recent years, but many individuals aged 80 years and older who are treated with Bruton tyrosine kinase inhibitors need to reduce their dose or discontinue therapy because of intolerance. And dose adjustments and discontinuations are even more likely for patients in their 90s. Dose reduction can lead to resistance in this setting.

One really needs to be in touch with the other things that are occurring in addition to the CLL in this patient group, and you have to scale the therapeutic intensity to match what you are treating. Treatment might be different for an 80-year-old patient vs a 95-year-old patient. These individuals should be offered therapies that target the specific problem that you are treating without being too intense. You do not want to ignore the issues, but you surely do not want to overtreat them either. Even a treatment as benign as rituximab can lead to poor outcomes in a 90-year-old patient whose compensatory mechanisms are already taxed.

The message for this patient group is to treat as gently as possible and choose the most effective therapy in light of their comorbidities. Also, these patients should be monitored very closely for diarrhea, headaches, bruising, and other adverse effects of treatment, and you should be ready to tailor your therapies and adjust the dosages if needed based on their response to treatment. For example, in an older patient with multiple treatment-limiting comorbidities who is being treated for lymphadenopathy, you might consider discontinuing therapy once the lymphadenopathy improves. 

Another example is treating an older individual with CLL and isolated anemia. Anemia in an 80-year-old patient might be from the CLL, but it might be driven more by a decreased production of erythropoietin as a consequence of renal insufficiency. In this situation, putting the patient on an erythropoietin-stimulating agent to resolve the anemia may be a better approach than offering a targeted therapy for their CLL. 

References

Autore F, Innocenti I, Corrente F, et al. Front-line therapy for elderly chronic lymphocytic leukemia patients: bendamustine plus rituximab or chlorambucil plus rituximab? Real-life retrospective multicenter study in the Lazio region. Front Oncol. 2020;10:848. doi:10.3389/fonc.2020.00848

Fresa A, Autore F, Galli E, et al. Treatment options for elderly/unfit patients with chronic lymphocytic leukemia in the era of targeted drugs: a comprehensive review. J Clin Med. 2021;10(21):5104. doi:10.3390/jcm10215104 

Halawi R, Moukhadder H, Taher A. Anemia in the elderly: a consequence of aging? Expert Rev Hematol. 2017;10(4):327-335. doi:10.1080/17474086.2017.1285695

Kasten-Jolly J, Lawrence DA. Differential blood leukocyte populations based on individual variances and age. Immunol Res. 2022;70(1):114-128. doi:10.1007/s12026-021-09257-6

Lipsky A, Lamanna N. Managing toxicities of Bruton tyrosine kinase inhibitors. Hematology Am Soc Hematol Educ Program. 2020;2020(1):336-345. doi:10.1182/hematology.2020000118 

Maddocks KJ, Ruppert AS, Lozanski G, et al. Etiology of ibrutinib therapy discontinuation and outcomes in patients with chronic lymphocytic leukemia. JAMA Oncol. 2015;1(1):80-87. doi:10.1001/jamaoncol.2014.218

Menjak IB, Giffoni de Mello Morais Mata D, Chesney TR, Haase KR. Predicting treatment toxicity in older adults with cancer. Curr Opin Support Palliat Care. 2021;15(1):3-10. doi:10.1097/SPC.0000000000000539

Stauder R, Eichhorst B, Hamaker ME, et al. Management of chronic lymphocytic leukemia (CLL) in the elderly: a position paper from an International Society of Geriatric Oncology (SIOG) task force. Ann Oncol. 2017;28(2):218-227. doi:10.1093/annonc/mdw547

John C. Byrd, MD

The Gordon and Helen Hughes Taylor Professor and Chair
Department of Internal Medicine
University of Cincinnati College of Medicine
Cincinnati, OH

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