Management of chronic lymphocytic leukemia (CLL) in the elderly: a position paper from an international Society of Geriatric Oncology (SIOG) Task Force

Abstract

Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is > 70 years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living and social support. Comorbidity scoring and geriatric assessment tools are helpful in achieving such multidimensional evaluation in a systematic manner. The introduction of new drugs including novel monoclonal antibodies and kinase inhibitors offers enhanced opportunities for the treatment of elderly patients with CLL. This position paper of a Task Force of the International Society of Geriatric Oncology (SIOG) reviews currently available evidence relevant to such patients. All types of elderly patient (i.e. chronological age > 65-70 years) are considered, from robust (fit) to vulnerable (unfit) to the terminally ill. Among the topics covered are the following: (i) the relationship between chronological age, prognosis and survival, (ii) assessment of biological aging, (iii) biological age as a determinant of treatment feasibility and tolerance and (iv) tailoring of both first and further-line treatment to the circumstances of the individual patient.

Real-world treatment and outcomes among older adults with chronic lymphocytic leukemia before the novel agents era

“…This older population is prone to a greater incidence and severity of comorbidities, as well as disease-and infection-related death, all of which may lead to delays in therapy initiation and poorer outcomes. [15][16][17][18] OS rates among all treated patients were modest (median 52.4 months for first-line therapy and 33.7 months for second-line therapy). Although our study does not permit causal inferences, we observed that rituximab monotherapy and rituximab-containing chemoimmunotherapy combinations were associated with favorable survival outcomes when compared to chlorambucil monotherapy in the front-line setting.…”

Structured assessment of frailty in multiple myeloma as a paradigm of individualized treatment algorithms in cancer patients at advanced age

“…5,[10][11][12] Although eligibility criteria for studies of anti-cancer/-MM agents have traditionally relied on age cut-offs and performance status, geriatric and MM-specific frailty assessments are just beginning to be incorporated into more accurate stratification plans of treatment algorithms. 6,7,11,12 Similarly to MM patients, geriatric assessments (GA) have been defined for patients with chronic lymphocytic leukemia (CLL) 8,13,14 and myelodysplastic syndrome (MDS), 15,16 where determination of frailty versus fitness has moved into clinical practice. However, solutions as to how they might be more uniformly used and valued in their daily pratice have not been fully determined.…”

In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI

“…2 However, CLL is mainly a disease of the elderly with many patients presenting at diagnosis with significant comorbidities that may affect treatment decisions and outcome. 3 Moreover, in recent years, the complex karyotype (CK) emerged as a prognostic biomarker associated with an inferior outcome 4,5 and worse response to treatments including novel drugs. 6,7 We therefore set out to analyze the prognostic relevance of comorbidities and of CK in relation to the CLL-IPI.…”

“…Indeed, relevant comorbidities may shorten life expectancy and may reduce treatment tolerance, 3,17 and modern treatment algorithms recommended evaluating not only age, clinical staging, and disease-specific prognostic biomarkers, but also comorbidities to guide clinical decisions, 13,18 particularly in the era of novel drugs. 19 However, the prognostic impact of comorbidities and of the CK in the era of mechanism-based treatment needs to be specifically addressed in larger series of patients treated for longer periods of time because in our cohort of CLL, these agents were offered only in more recent years.…”