This study presents a cohort of older patients with NHL evaluated using a systemic CGA protocol to enable individualized oncospecific treatment. The goal of our research was to determine if the application of a systemic CGA protocol in elderly patients with a recent diagnosis of lymphoma could enable patient classification according to frailty profiles, prescription of geriatric care recommendations, and tailored oncospecific treatment. We also aimed to describe the impact of CGA on clinical outcomes.
CGA yielded exhaustive information on patients’ functional capacity, comorbidity, level of frailty, nutritional status, cognitive status, geriatric syndromes, and estimated survival. These data allowed us to classify patients into three groups (type I, II, and III-IV). Although no differences were observed regarding the types of lymphoma diagnosed across groups, patient classification permitted individualized care, including personalized geriatric recommendations to improve nutritional status, improve physical condition, and control vascular risk factors, as well as frailty-based adaptation of oncospecific treatments. During follow-up, rates of toxicity were similar for the different groups, but mortality rates and frailty among surviving patients were significantly higher in the type III-IV group.
Previous attempts have been made to classify older patients with lymphoma according to non-hematologic characteristics. However, there is no definitive consensus on the most appropriate instruments, scores, or scales for classification. Some studies (most of which have been performed in an older population with diffuse large B-cell lymphoma) have identified a series of prognostic factors associated with worse clinical outcomes and lower survival, using domains such as functional impairment, dependence for basic or instrumental activities, presence of malnutrition and comorbidity [35–36]. Tools focusing on these domains are capable of identifying frailty more accurately than clinician judgment or performance status (PS) alone [37].
Existing studies seeking to predict unfavorable outcomes in older patients with lymphoma include research published by the Italian Lymphoma Foundation [38] (FIL), featuring a simplified geriatric assessment including basic and instrumental activities of daily living, comorbidity, and age, and Miura et al study [39] describing the development of the ACA Index to predict outcomes using age, comorbidity, and serum albumin level. Liu et al [40] combined the ACA index with an assessment of functional status (IADL) to create the IADL-ACA (IACA) index in patients ≥ 65 years of age with diffuse large B-cell lymphoma, permitting patient classification into three risk groups - low, intermediate, and poor - with significant differences observed regarding overall response rate, cumulative incidence of treatment-related mortality, relapse rate, and 2-year overall survival. Although our study did not aim to create a predictive score, we were able to detect different areas that can help to classify older patients with lymphoma and that could potentially serve as a basis for the creation of predictive models using a larger series.
Two aspects of our study deserve to be highlighted. On the one hand, frailty detection through CGA revealed unmet needs that warranted geriatric intervention to improve patients’ general health status. These interventions (physical exercise programs, nutritional support, and psychological interventions) have also been carried out in other cancer settings and have been described as positively influencing patient outcomes[41–42]. On the other hand, the information gathered through CGA and patient classification allowed the lymphoma committee to tailor treatment to each patient. To the best of our knowledge, this is the first study reporting the systematic individualization of oncospecific treatment according to patients’ frailty status. For example, in Tucci’s study [38], patients were treated according to the attending physician’s clinical judgement regardless of category, while Garrick et al [43] report that the influence of frailty on the choice of treatment was minor, leading to a change of hematological treatment in only 21.7% of cases.
Adjusting treatment according to patients’ characteristics allowed us to achieve a higher percentage of complete responses in type I and II patients, without increased toxicity, use of health resources, or need for treatment across groups. These results indicate the appropriateness of initial treatment adaptations decided upon by the lymphoma committee. Other studies, such as Corre et al [44], have demonstrated similar results in advanced non-small-cell lung cancer, with CGA-based individualized treatment failing to improve treatment outcomes but slightly reducing treatment toxicity. Mohile et al [45] report that older patients with advanced cancer undergoing CGA (incurable solid tumors or lymphoma) experience less grade 3–5 toxicity than their non-CGA counterparts. These studies highlight the importance of CGA-guided interventions to improve outcomes, although more specific studies are needed to determine how CGA-tailored treatment can reduce toxicity for older individuals with lymphoma.
Strengths of this study include the thoroughness with which geriatric assessment was performed, and the close clinical follow-up patients received during treatment. We believe that the presence of comprehensive geriatric assessment carried out by an expert physician, instead of the exclusive use of frailty scales, is one of the greatest strengths of the study. In our opinion, CGA-mediated patient selection enabled the lymphoma committee to carry out comprehensive evaluation and therapeutic decision-making, while geriatric intervention during oncospecific treatment played an important role in the study results.
One of our study’s limitations is the lack of a control group, which could have helped us to understand the implications of this care strategy better. Moreover, we cannot draw robust conclusions regarding different lymphoma subtypes due to the small sample size. To overcome these limitations, prospective randomized trials using CGA as a stratum criterion should be planned. We expect further validation of the efficacy of CGA-based therapy across different lymphoma subgroups in future.
In conclusion, the oncohematogeriatric approach to care using CGA permits geriatric intervention in older patients with lymphoma, classifies patients according to their frailty status, and aids the decision-making process by permitting individualized treatment tailored to patients’ overall condition and personal preferences. Our results reinforce the value of multidisciplinary teams that include geriatricians to personalize oncospecific therapy according to the clinical, functional and frailty status of each patient. This study is one of the first to demonstrate oncohematogeriatric assessment and intervention and its influence on treatment outcomes.
We propose incorporating a CGA protocol and ensuring the presence of geriatricians as part of a multidisciplinary care team as part of the optimal therapeutic strategy for older patients with lymphoma. If multidisciplinary or geriatric inputs are not available, it is important to design a predefined intervention plan [46] for these patients. Moving forward, there is a need for further studies on the role of CGA regarding prognosis and management of older adults with lymphoma. Future randomized studies should focus on providing evidence for optimal therapeutic options guided by geriatric assessment.