Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study.

Purpose Cancer-related cognitive impairment (CRCI) is an important clinical problem in patients with breast cancer receiving chemotherapy. Nationwide longitudinal studies are needed to understand the trajectory and severity of CRCI in specific cognitive domains. Patients and Methods The overall objective of this nationwide, prospective, observational study conducted within the National Cancer Institute Community Clinical Oncology Research Program was to assess trajectories in specific cognitive domains in patients with breast cancer (stage I-IIIC) receiving chemotherapy, from pre- (A1) to postchemotherapy (A2) and from prechemotherapy to 6 months postchemotherapy (A3); controls were assessed at the same time-equivalent points. The primary aim assessed visual memory using the Cambridge Neuropsychological Test Automated Battery Delayed Match to Sample test by longitudinal mixed models including A1, A2, and A3 and adjusting for age, education, race, cognitive reserve score, and baseline anxiety and depressive symptoms. We also assessed trajectories of CRCI in other aspects of memory as well as in attention and executive function with computerized, paper-based, and telephone-based cognitive tests. Results In total, 580 patients with breast cancer (mean age, 53.4 years) and 363 controls (mean age, 52.6 years) were assessed. On the Delayed Match to Sample test, the longitudinal mixed model results revealed a significant group-by-time effect ( P < .005); patients declined over time from prechemotherapy (A1) to 6 months postchemotherapy (A3; P = .005), but controls did not change ( P = .426). The group difference between patients and controls was also significant, revealing declines in patients but not controls ( P = .017). Several other models of computerized, standard, and telephone tests indicated significantly worse performance by patients compared with controls from pre- to postchemotherapy and from prechemotherapy to 6 months postchemotherapy. Conclusion This nationwide study showed CRCI in patients with breast cancer affects multiple cognitive domains for at least 6 months postchemotherapy.