Publications

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

OBJECTIVE

To compare the cost-effectiveness of 3 common alternate treatments for depression.

METHODS

The cost-effectiveness analysis was conducted as part of a randomized clinical trial, the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) trial, in which patients were randomized from December 2012 to May 2015 and followed for 12 weeks in 35 Veterans Affairs medical centers. Depression diagnosis was based on ICD-9 codes. Patients were randomized to standard antidepressant therapy augmented with aripiprazole, standard antidepressant therapy augmented with bupropion, or switch to bupropion. Remission was measured using the 16-item Quick Inventory of Depressive Symptomatology-Clinican Rated. Outcomes included the incremental cost-effectiveness ratio (ICER) comparing costs per remission and costs per quality-adjusted life-year (QALY) with 12 weeks as the time horizon using the health care sector perspective.

RESULTS

The mean age of participants enrolled in the trial (N = 1,522) was 54 years, and participants were predominantly male. The rate of remission at 12 weeks was highest for the aripiprazole augmentation arm (29%), followed by bupropion augmentation (27%), and lowest for switching to bupropion (22%). Switching to bupropion was strongly dominated by bupropion augmentation at an ICER of -$640/remission (95% CI, -$5,770 to $3,008). The ICER for the aripiprazole augmentation versus switching to bupropion was $1,074/remission (95% CI, $47 to $5,022), and the ICER for aripiprazole augmentation versus bupropion augmentation was $5,094/remission (95% CI, -$34,027 to $32,774). There were no significant differences in QALYs, mental health care costs, employment, or other work and social adjustment outcomes between treatment groups.

CONCLUSIONS

In treatment of depression with less than optimal response, augmentation with either aripiprazole or bupropion was cost-effective relative to switching to bupropion.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT01421342.

Activated phosphoionositide-3 kinase delta syndrome (APDS) is a rare disorder caused by activating mutations in phosphoionositide 3-kinase delta (PI3Kδ). This syndrome usually presents in childhood with recurrent sinopulmonary infections and immune deficiency as is seen in the case discussed in this report. Patients with APDS also experience other complications including lymphoid hyperplasia, autoimmunity, increased susceptibility to herpes viruses, especially Epstein-Barr virus and cytomegalovirus, and an increased incidence of B-cell lymphoma. The clinical implications for lymphoid hyperplasia and lymphoma are profound and frequently, it is challenging to distinguish between the two. This case report is of a young girl with a mutation in PIK3CD, the gene encoding the catalytic subunit of PI3Kδ, who presents with asymmetrical cervical lymphadenopathy and parotid swelling. After little improvement in lymphadenopathy on antibiotics, an excisional biopsy of a cervical lymph node was obtained which was initially concerning for lymphoma. This case recounts the clinical decisions made to evaluate this lymphadenopathy and concern for malignancy due to the increased incidence of B-cell lymphoma in this population. It was concluded after careful evaluation of her lymph node histology and cytometry, bone marrow biopsy, and CSF studies that her findings were consistent with lymphoid hyperplasia and not lymphoma and she was treated with rituximab. This case highlights the many comorbidities present in patients with this disease and the current treatments for complications in patients with APDS, including new targeted therapies.