Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL.

BACKGROUND: Subgroups of patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) exhibit suboptimal outcomes after standard therapies, including oral kinase inhibitors. We and others have previously reported on safety and efficacy of autologous CD19-targeted CAR T-cells for these patients; here we report safety and long-term follow-up of CAR T-cell therapy with or without conditioning chemotherapy for patients with R/R CLL and indolent B-cell non-Hodgkin lymphoma (B-NHL). METHODS: We conducted a phase 1 clinical trial investigating CD19-targeted CAR T-cells incorporating a CD28 costimulatory domain (19-28z). Seventeen of 20 patients received conditioning chemotherapy prior to CAR T-cell infusion. Five patients with CLL received ibrutinib at the time of autologous T-cell collection and/or CAR T-cell administration. RESULTS: This analysis included 16 patients with R/R CLL and 4 patients with R/R indolent B-NHL. Cytokine release syndrome (CRS) was observed in all 20 patients but grades 3 and 4 CRS and neurological events were uncommon (10% for each). Ex vivo expansion of T-cells and proportions of CD4+/CD8+ CAR T-cells with CD62L+CD127+ immunophenotype were significantly greater in patients on ibrutinib at leukapheresis. Three of 12 evaluable CLL patients receiving conditioning chemotherapy achieved CR (two had minimal residual disease-negative CR). All patients achieving CR remained progression-free at median follow-up of 53 months. CONCLUSION: Conditioning chemotherapy and 19-28z CAR T-cells were acceptably tolerated across investigated dose levels in heavily pretreated patients with R/R CLL and indolent B-NHL, and a subgroup of patients achieved durable CR. Ibrutinib therapy may modulate autologous T-cell phenotype. TRIAL REGISTRATION: ClinicalTrials.gov NCT00466531. FUNDING: Juno Therapeutics.

Complementary and alternative medicine provider use and expenditures by cancer treatment phase.

OBJECTIVE: To assess the use of complementary and alternative medicine (CAM) providers and the associated expenditures by specific treatment phases among patients with cancer. STUDY DESIGN: Cross-sectional analysis of medical services utilization and expenditures during the 3 therapeutic phases of initial, continuing, and end-of-life life treatment. METHODS: Analysis of an insurance claims database that had been matched to the Washington State Surveillance, Epidemiology, and End Results cancer registry. RESULTS: Of 2900 registry-matched patients, 63.2% were female, the median age was 54 years, and 92.7% were of white race/ethnicity. Breast cancer was the most frequent diagnosis (52.7%), followed by prostate cancer (24.7%), lung cancer (10.1%), colon cancer (7.0%), and hematologic malignancies (5.6%). Patients using CAM providers represented 26.5%. The proportion of patients using CAM was similar during each treatment phase. All patients used some conventional care. Age, female sex, breast cancer diagnosis, and white race/ethnicity were significant predictors of CAM use. Diagnosis of a musculoskeletal problem occurred at some time during the study for 72.1% of patients. CAM provider visits represented 7.2% of total outpatient medical visits, and 85.1% of CAM visits resulted in a musculoskeletal diagnosis. Expenditures for CAM providers were 0.3%, 1.0%, and 0.1% of all expenditures during the initial, continuing, and end-of-life phases, respectively. CONCLUSIONS: For patients with cancer, musculoskeletal issues were the most commonly listed diagnosis made by a CAM provider. Although expenditures associated with CAM are a small proportion of the total, additional studies are necessary to determine the importance that patients place on access to these services.