Tedeschi, Alessandra

Abstract Advancements in the understanding of chronic lymphocytic leukemia (CLL) have transformed patient care, leading to the development of novel targeted therapies. Traditionally, patient fitness for treatment was based on the tolerability of chemoimmunotherapy such as fludarabine–cyclophosphamide–rituximab. As the CLL patient population is predominantly older, age has historically been a major factor in how a physician selects a patient's treatment. However, as a patient's fitness goes beyond age, the definition of patient fitness should also evolve. Here, we provide suggestions for the current best practice on assessing fitness for treating CLL. Considerations for treatment include assessment of polypharmacy, history of infections, cardiovascular and renal comorbidities, functional status, cognitive and psychological status, nutritional status, and social support. The flow of assessments can start with a typical clinical evaluation followed by geriatric, cardiovascular, and renal reviews, if needed, and include collecting a patient's full history to evaluate their risk of complications with specific CLL treatments. The severity of a patient's cardiovascular profile can range from low to high risk; for those at high risk, collaboration with a cardiologist is recommended. Geriatric assessment is advised to determine baseline frailty and resilience to tolerate treatments, to avoid inappropriate treatment or undertreating patients based on chronological age, and to align the patient's fitness status with the most optimal treatment. Continuous monitoring and assessment, regardless of therapy, are recommended. Patient preferences are also integral to this decision‐making process. Looking beyond a patient's age and basing treatment selection on their fitness is key in the new era of treatment in CLL.

Abstract The treatment of patients with Bing-Neel syndrome (BNS) is not standardized. We included patients with Waldenström macroglobulinemia (WM) and a radiologic and/or cytologic diagnosis of BNS treated with ibrutinib monotherapy. Response assessment was based on criteria for BNS from the 8th International Workshop for WM. Survival from BNS diagnosis (BNS survival), survival from ibrutinib initiation to last follow-up or death (ibrutinib survival), and time from ibrutinib initiation to ibrutinib discontinuation for toxicity, progression, or death (event-free survival [EFS]) were estimated. Twenty-eight patients were included in our study. The median age at BNS diagnosis was 65 years. Ibrutinib was the first line of treatment for BNS in 39% of patients. Ibrutinib was administered orally at a dose of 560 and 420 mg once daily in 46% and 54% of patients, respectively; symptomatic and radiologic improvements were seen in 85% and 60% of patients within 3 months of therapy. At best response, 85% of patients had improvement or resolution of BNS symptoms, 83% had improvement or resolution of radiologic abnormalities, and 47% had cleared the disease in the cerebrospinal fluid. The 2-year EFS rate with ibrutinib was 80% (95% confidence interval [CI], 58%-91%), the 2-year ibrutinib survival rate was 81% (95% CI, 49%-94%), and the 5-year BNS survival rate was 86% (95% CI, 63%-95%). Ibrutinib therapy is effective in patients with BNS and should be considered as a treatment option in these patients.