Nonhematologic toxicity of imatinib mesylate in pediatric patients with chronic myelogenous leukemia: a predominance of musculoskeletal pain.

Therapy with the tyrosine kinase inhibitor imatinib mesylate has become standard initial treatment for adult and pediatric patients with chronic myelogenous leukemia. Long-term follow-up data are now available in the adult population, and the toxicity profile of imatinib mesylate among adults has been extensively studied and reported. Despite its increasing use in the pediatric population, there are limited data regarding adverse event profiles of imatinib mesylate in children, and few reports exist in the literature focusing on nonhematologic toxicity in this population. We reviewed our institutional experience with imatinib therapy for chronic myelogenous leukemia over an 8-year period of time. Nine pediatric patients began therapy with imatinib mesylate and were included in this review. We reviewed the occurrence of nonhematologic toxicity in this cohort and the impact of that toxicity on continuation of therapy. Eight patients experienced nonhematologic toxicity, including nausea/vomiting (44.4%) and musculoskeletal pain (88.9%). Three patients (33.3%) required discontinuation of imatinib therapy due to grade 3/4 musculoskeletal pain, a rate that is significantly higher than that seen in the adult population. As imatinib therapy becomes increasingly widespread in the treatment of pediatric malignancies, there may be different patterns of clinically significant nonhematologic toxicity, including higher grade musculoskeletal pain.

The Connect CLL Registry: final analysis of 1494 patients with chronic lymphocytic leukemia across 199 US sites.

Optimal treatment of chronic lymphocytic leukemia (CLL) remains unclear. The Connect CLL Registry, a United States-based multicenter prospective observational cohort study, enrolled 1494 patients between 2010 and 2014 from predominantly community-based settings. Patients were grouped by line of therapy (LOT) at enrollment. With a median follow-up of 46.6 months (range, 0-63.0 months), median overall survival (OS) was not reached in LOT1, 63.0 months (95% confidence interval [CI], 46.0-63.0 months) in LOT2, and 38.0 months (95% CI, 33.0-47.0 months) in LOT≥3. Bendamustine and rituximab (BR; 33.5%); fludarabine, cyclophosphamide, and rituximab (FCR; 21.4%); and rituximab monotherapy (18.5%) were the most common regimens across LOTs. Median event-free survival (EFS) was similar in patients treated with BR (59.0 months) and FCR (55.0 months) in LOT1; median OS was not reached. In multivariable analysis, BR or FCR vs other treatments in LOT1 was associated with improved EFS (hazard ratio [HR], 0.60; P < .0001) and OS (0.67; P = .0162). Using the Kaplan-Meier product limit, ibrutinib vs other treatments improved OS in LOT2 (HR, 0.279; P = .009), LOT3 (0.441; P = .011), and LOT≥4 (0.578; P = .043). Prognostic modeling of death at 2 years postenrollment identified 3 risk groups: low (mortality rate, 6.2%), medium (14.5%), and high (27.4%). The most frequent adverse events across LOTs were pneumonia (11.6%) and febrile neutropenia (6.2%). These data suggest that advantages of LOT1 FCR over BR seen in clinical trials may not translate to community practice, whereas receiving novel LOT2 agents improved outcomes. This trial was registered at www.clinicaltrials.gov as NCT01081015.