Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia: Geriatric Assessment and Support During Treatment
There is no geriatric assessment tool to determine whether an older frail patient with chronic lymphocytic leukemia (CLL) is best suited for one specific novel therapy over another. Once a therapy is chosen, guidance on what to expect with side effects can help support patients during treatment.
“The choice of specific novel therapies for older patients with CLL is informed by clinical judgment and experience, in addition to the available data.”
There is no geriatric assessment tool that is considered to be the standard of care for older patients with CLL. The Cumulative Illness Rating Scale (CIRS) is mainly used in clinical trials. It calculates a comorbidity score rather than a functional score, and it was popularized by the results of large randomized trials from Germany in which the dual eligibility factors of a high comorbidity score and low kidney function were used to define an unfit group. More recently, the CLL14 trial by Al-Sawaf and colleagues used a CIRS score of greater than 6, a creatinine clearance of 30 to 69 mL/min/1.73 m2, or both to determine eligibility, an approach resulting in a median age of approximately 72 years in that study.
While the CIRS can be useful in clinical trials, it is not used in clinical practice, even at academic centers. It is also less relevant now that we have more treatment options beyond chemoimmunotherapy. In the age of small molecules, treatment is much better tolerated in older people vs when chemotherapy was the only option because, except for neutropenia with venetoclax, novel agents do not cause myelosuppression. This is important, as significant myelosuppression is much more likely to result in infections in older patients and the consequences of such infections are much greater in this population. Serious infections in older patients can result in an extended hospital stay, deconditioning, and the need to go to rehab.
Thus, the choice of specific novel therapies for older patients with CLL is informed by clinical judgment and experience, in addition to the available data. While the time-limited venetoclax-based regimens tend to be associated with fewer adverse events than ibrutinib, there are no specific data to guide us, in general, when choosing a particular agent over another among older patients with comorbidities or those who may be frail. You also have to look at each individual comorbidity.
Once the patient begins treatment, there are certainly areas in which we can support them. I think that, with Bruton tyrosine kinase inhibitors for example, it helps to make the patient aware that most of the annoying toxicities, such as arthralgia, diarrhea, mouth sores, and cramps, get better with time. This is an important way to help support the patient through treatment. If an individual has mouth sores that cause pain when eating and drinking, they might begin to think that they are going to have to endure these symptoms for years and thus decide that their current therapy is not for them. I recently had a patient who told me something like, “You said to me, ‘all of this will be gone by 6 months,’ and you know what? It’s gone.” So, that was very rewarding to hear. I think that if this particular patient was envisioning that this side effect was going to last for 5 years, they would then understandably not want to continue with the drug.
Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 4-year follow-up analysis of the randomized CLL14 study [abstract S146]. Abstract presented at: European Hematology Association 2021 Virtual Congress; June 9-17, 2021.
Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21(9):1188-1200. doi:10.1016/S1470-2045(20)30443-5
Farooqui AA, Ashraf A, Farooq TB, et al. Novel targeted therapies for chronic lymphocytic leukemia in elderly patients: a systematic review. Clin Lymphoma Myeloma Leuk. 2020;20(7):e414-e426. doi:10.1016/j.clml.2020.02.013
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Rice J, Nipp RD, Lage DE, et al. Association between baseline geriatric domains and survival in older adults with chronic lymphocytic leukemia (CLL) [abstract 12041]. Abstract presented at: 2021 American Society of Clinical Oncology Annual Meeting; June 4-8, 2021.
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