Patients with B-cell hematologic malignancies who progress through first- or second-line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T-cell expansion. The major toxicity associated with CAR T-cell infusions is cytokine release syndrome (CRS), a potentially life-threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment-related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab-refractory patients. Other toxicities of CAR T-cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients' medications is imperative to eliminate medications that may contribute to treatment-related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long-term follow-up will help establish the place of CAR T cells in therapy.

Pharmacy residency training programs are essential for pharmacists that will primarily engage in direct patient care activities. This annotated bibliography includes key publications that provide evidence of the value that pharmacy residents provide to the sponsoring health system. This manuscript will aid prospective residency directors interested in developing new residency positions at new institutions or for residency program directors interested in expanding the total number of resident positions available at the existing sites.

Over the last decade, numerous drug therapies have emerged for the treatment of multiple myeloma including immunomodulating agents namely thalidomide, lenalidomide, and pomalidomide and proteasome inhibitors namely bortezomib and carfilzomib. These agents have transformed the treatment of multiple myeloma and the role of high-dose chemotherapy followed by stem cell transplantation in the treatment of the disease. There are now studies that evaluate the use of drug therapy as maintenance following autologous stem cell transplantation; these studies have shown improvements in surrogate endpoints such as progression-free survival. Studies that have evaluated thalidomide or lenalidomide maintenance therapy have demonstrated an overall survival (OS) benefit in individuals with multiple myeloma who received high-dose chemotherapy followed by stem cell transplantation. A meta-analysis of thalidomide maintenance therapy did show a possible late survival benefit. The use of dexamethasone, thalidomide, lenalidomide, or combination bortezomib with thalidomide in patients who did not undergo transplantation demonstrated progression-free survival benefit; although there was no OS advantage for these agents in this population. There are a number of important considerations when selecting a drug therapy strategy for maintenance therapy which includes practical considerations such as route of administration and frequency of administration. Additionally, patient-specific elements such as potential toxicities, end-organ function, quality of life, cytogenetics, and previous treatment should be considered. Additional studies are needed to elicit the timing for initiation and duration of maintenance therapy, determine the role of cytogenetics, further characterize possible resistance patterns, and determine the combinations necessary to achieve an optimal increase in OS. Until more data are available, the risks and benefits should be evaluated on a patient-specific basis when deciding to initiate maintenance therapy or observation.

Patients with immunoglobulin light chain (AL) amyloidosis undergoing peripheral blood hematopoietic stem cell (PBSC) mobilization for autologous hematopoietic stem cell transplantation (auto-HCT) can experience significant morbidity and mortality. The purpose of this study was to characterize the adverse events and identify prognostic factors associated with the development of morbidity and mortality in patients with AL amyloidosis who had begun PBSC mobilization for auto-HCT. A retrospective study was performed in 101 consecutive patients with AL amyloidosis who underwent PBSC mobilization for auto-HCT between January 2006 and December 2013. A composite primary endpoint of morbidity and mortality during PBSC mobilization was used. Forty-one patients (41%) experienced at least 1 adverse event, including 4 deaths during PBSC mobilization. Adverse events included in this composite endpoint were cardiac events, thromboembolic events, bleeding events, unplanned hospitalization, weight gain >2% necessitating diuretic intervention, and death. Low serum albumin levels, elevated N-terminal pro-brain natriuretic peptide, and increased interventricular septal thickness were significantly associated with the composite primary endpoint (P = .024, .001, and .006, respectively). The median progression-free survival from the start of PBSC mobilization was 4.7 years, and the median overall survival was 6.5 years. In general, PBSC mobilization is associated with minimal complications, but patients with AL amyloidosis can experience more frequent and severe complications, such as volume overload and weight gain. Careful patient selection is warranted in patients with AL amyloidosis before proceeding to PBSC mobilization and auto-HCT.

Purpose As a result of the leucovorin shortage, we switched from BSA-adjusted to low fixed-dose leucovorin in patients with colon cancer receiving fluorouracil-containing therapy. Methods A retrospective, pilot study of adults receiving intravenous leucovorin as part of a fluorouracil-containing treatment was conducted including individuals with stage II or III colon or newly diagnosed metastatic colorectal cancer. One low fixed-dose (leucovorin 50 mg) patient was matched by the investigator to one BSA-adjusted (leucovorin 200-500 mg/m/dose) patient on disease stage and age. The objectives were to compare cost of alternative dosing strategies as well as efficacy and adverse event rates. Only patients being treated in the first-line metastatic colorectal cancer setting were included in the efficacy analysis. Results Fifty-eight patients were included. Leucovorin cost was reduced by 7- to 14-fold, and we were able to conserve a total of 1580-3400 doses of leucovorin by changing to fixed-dose (estimated from 200 mg/m or 400 mg/m dosing strategies, respectively). No statistically significant differences in progression-free survival ( p = 0.254), overall survival ( p = 0.923), or complications resulted. Conclusion Our decision to reduce the dose of leucovorin allowed us to conserve supply and control cost. The small sample size did not allow us to detect differences in efficacy or adverse event rates, and thus a larger study would be required to confirm our findings that efficacy was not compromised nor adverse effects greater.