Christopher Keir

Impact of low-grade adverse events on health-related quality of life in adult patients receiving imatinib or nilotinib for newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase

Abstract Objective: Chronic myeloid leukemia (CML) treatment relies on tyrosine kinase inhibitors (TKIs), but their use can be associated with low-grade adverse events (AEs). This analysis aimed to identify the low-grade AEs which significantly impact the Health Related Quality of Life (HRQoL) of CML patients in chronic phase (CP) and to compare the incidence of such AEs among nilotinib- and imatinib-treated patients. Research design and methods: Data from the 48 month ENESTnd trial were used (N = 593 patients). HRQoL was assessed using generic (SF-36) and leukemia-specific (FACT-Leu) HRQoL surveys. AEs were categorized into 26 system organ classes. Results: In the adjusted regression model, five low-grade AE categories – gastrointestinal disorders, blood and lymphatic system disorders, general disorders and administration site conditions, musculoskeletal disorders, and psychiatric disorders – significantly impaired at least one HRQoL score. The incidence rate of these five AE categories was either significantly lower for nilotinib than imatinib or not different between the two drugs. The AE categories with lower incidence for both nilotinib 300 mg BID and 400 mg BID versus imatinib 400 mg daily were gastrointestinal, blood and lymphatic system, and musculoskeletal; nilotinib 300 mg BID had lower incidence than imatinib for general disorders. Limitations: Low-grade AEs were grouped and analyzed by system organ class category, so the effect of some rare individual AEs on HRQoL may have been missed. Conclusions: The impact of low-grade AEs on HRQoL should be taken into account, along with other factors, when selecting the optimal treatment for patients newly diagnosed with CML-CP.

Building blocks for institutional preparation of CTL019 delivery

Chimeric antigen receptor (CAR) T-cell therapy is an investigational immunocellular therapy that reprograms a patients cytotoxic T cells to engage and eliminate malignant cells. CAR T-cell therapies targeting the CD19 antigen have demonstrated high efficacy in clinical trials for patients with B-cell malignancies and may potentially be available on a broader scale in the future. CAR T-cell therapy begins with the collection of a sufficient number of T cells from a patients peripheral blood through leukapheresis. Several factors must be considered when patients undergo leukapheresis for CAR T-cell therapy, including age and prior therapies. The leukapheresis material is shipped to a manufacturing facility, followed by return of the CAR T cells to the treatment center. Careful coordination of a multidisciplinary team composed of physicians, nurses, pharmacists and other hospital personnel is critical for the proper care of the patient before, during and after CAR T-cell therapy. CAR T-cell therapy has been associated with adverse events (AEs) such as cytokine release syndrome, which requires rapid attention by the emergency department, intensive care unit and hospital pharmacy. In this review, we discuss several aspects of institutional preparation for leukapheresis, CAR T-cell infusion and AE management based on our experience with clinical trials of the CD19 CAR T-cell therapy CTL019.

Survival after stem-cell transplant in pediatric and young-adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia

Abstract Objective: Allogeneic stem-cell transplant (allo-SCT) is the standard of care for pediatric patients with acute lymphoblastic leukemia (ALL) who relapse after frontline chemotherapy; however, for patients who relapse after allo-SCT, outcomes are very poor. Few studies have examined overall survival in this patient population, particularly in patients who received a second allo-SCT. Methods: This was a retrospective analysis using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. The study population included patients aged 3 to 21 years who were diagnosed with B-ALL and underwent their first allo-SCT between 2009 and 2013. The primary endpoint was the time from the date of posttransplant relapse to the date of death due to any reason. Results: Outcomes in 1349 pediatric and young-adult patients were included in this analysis. The Kaplan–Meier estimated probability of survival at 3 years after first allo-SCT was 63.1% (95% CI, 60.2%–65.8%). Overall, 29.2% of patients relapsed after first allo-SCT and had a median survival of 7.4 months (95% CI, 6.0–9.6 months). Twenty-five patients in the analysis developed secondary malignancies, most of which were lymphoproliferative disorders. Conclusions: Survival rates are low in pediatric and young-adult patients who relapse after first and second allo-SCT, and new therapies are needed to improve outcomes in this population. This data can be used as a historical comparison for single-arm trials of novel therapies for this patient population, including chimeric antigen receptor T-cell therapy.

The economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who have received adjuvant imatinib therapy.

Abstract Objective: To estimate the economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who received imatinib adjuvant therapy. Methods: Data from the MarketScan and PharmMetrics databases between January 2000 and March 2013 were extracted. Patients who had received at least one diagnosis of GIST, had undergone a primary surgery for GIST, and had received at least one prescription for imatinib were included in the analysis. An algorithm was applied to identify those who had a subsequent GIST recurrence. Patients who experienced a recurrence and those who did not have a recurrence were compared for differences in healthcare utilization measures and healthcare costs within 6 months after the recurrence, while adjusting for potential confounding factors. Results: A total of 540 patients with primary resectable GIST who received imatinib adjuvant therapy were identified, including 444 (82.2%) patients who did not experience GIST recurrence and 96 (17.8%) patients who did experience recurrence. Patients who experienced GIST recurrence utilized significantly more healthcare resources in all categories than patients who did not have a recurrence, including the number of hospitalizations, days of hospitalization, emergency room visits, outpatient visits, and other medical services (all p-values <0.01). The total healthcare cost was significantly higher for patients with GIST recurrence, with a difference of

False-positive results with select HIV-1 NAT methods following lentivirus-based tisagenlecleucel therapy

4464 per patient per month (p < 0.01). Both the medical and pharmacy costs were significantly higher with adjusted differences of

Global Manufacturing of CAR T Cell Therapy

3488 and

Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study.

1423 per patient per month, respectively (both p-values <0.01). Conclusions: Patients who had GIST recurrence after surgical resection incurred significantly more healthcare resource utilization and greater healthcare costs within 6 months after the recurrence than patients who did not have recurrence. These findings suggest that GIST recurrence is associated with a substantial economic burden.

Treatment-free remission (TFR) following nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTfreedom, ENESTop, ENESTgoal, and ENESTpath.

TO THE EDITOR: Genetically reprogrammed T-cell therapy is a novel treatment approach being investigated in various hematologic malignancies, including relapsed and refractory pediatric B-cell acute lymphoblastic leukemia (B-ALL), multiple myeloma, diffuse large B-cell lymphoma, and chronic