Retrospective review of the toxicities and change in dosing patterns for pegaspargase in patients with acute lymphoblastic leukemia/lymphoma and T-cell lymphoma.

INTRODUCTION: Pegaspargase (PEG) is a key component of standard regimens for acute lymphoblastic leukemia/lymphoma (ALL) and extranodal natural killer/T-cell lymphoma (NKTCL). Emerging evidence suggests an opportunity to decrease incidence of PEG-associated toxicities with dose capping, but evidence is limited. This study aims to evaluate whether a significant difference in PEG-associated toxicities related to dosing strategy exists and to identify patient-specific or regimen-specific factors for PEG-related toxicity. METHODS: A retrospective analysis of PEG-associated toxicities was completed in adult patients with ALL or NKTCL who received PEG within Cancer and Leukemia Group B (CALGB) 10403 or modified dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide (mSMILE) regimens at the UW Medical Center/Fred Hutchinson Cancer Center. PEG-associated toxicities that occurred through 8 weeks after PEG doses were noted. RESULTS: Twenty-eight patients received dose-capped PEG, and 29 received noncapped PEG. Fewer all-grade and grade 3/4 toxicities were observed in the dose-capped cohort. Grade 3/4 toxicities observed were hepatotoxicity, hyperglycemia, hypersensitivity, and hypertriglyceridemia. In addition, fewer grade 3/4 pancreatitis and thrombosis events occurred in the dose-capped cohort. Hypertriglyceridemia and hepatotoxicity were associated with the highest cumulative incidence proportions among all toxicities. CONCLUSION: Dose capping of PEG was associated with a similar or later median onset for most toxicities, a less heterogeneic toxicity profile, and a lower recurrence of most toxicities upon PEG rechallenge compared to the non-dose-capped cohort. Standardizing PEG dose capping in the CALGB 10403 and mSMILE regimens may translate to improved tolerance compared to a historical standard of no dose capping PEG.

Venetoclax as a therapeutic option for the treatment of chronic lymphocytic leukemia: the evidence so far.

INTRODUCTION: Venetoclax, an oral, BCL-2 inhibitor, is approved by the FDA for treatment of CLL in all lines of therapy. Data from landmark studies, including the CLL14 and MURANO trials, demonstrated marked improvement in clinical outcomes compared to chemoimmunotherapy when venetoclax was used in combination with CD20 monoclonal antibodies for fixed treatment duration. AREAS COVERED: This article reviews the mechanism of action of venetoclax and discusses how curtailing the BCL signaling pathway undermines CLL pathophysiology. The authors also give their clinical experience with the drug, with emphasis on assessing and managing the risk of venetoclax-associated tumor lysis syndrome (TLS). EXPERT OPINION: Venetoclax has positioned itself as one of the primary treatment options for CLL, given the consistent efficacy and deep remissions it has elicited across multiple settings of the disease with a time-limited schedule. Accurate TLS risk evaluation and stringent adherence to the dose-escalation protocols will help optimize patient outcomes. Finally, we expect that current and future studies will (1) ascertain the ideal treatment duration using the minimal residual disease state as a guide and (2) help us understand the optimal role of venetoclax in combination or in sequence with other novel targeted therapies in the treatment of CLL.

Establishing clinical pharmacist telehealth services during the COVID-19 pandemic.

PURPOSE: After community transmission of the novel virus that causes coronavirus disease 2019 (COVID-19) was detected in the State of Washington in February 2020, innovative measures, such as telehealth appointments, were needed to safely continue to provide optimal pharmaceutical care for patients with chronic conditions and cancer. SUMMARY: Prior to the COVID-19 pandemic, federal regulations limited the scope of telehealth pharmacist services. However, enactment of the Coronavirus Preparedness and Response Supplemental Appropriations Act, followed by guidance by the Centers for Medicare and Medicaid Services and the Department of Health and Human Services, allowed currently credentialed providers (including pharmacists) to continue to provide patient care services via telehealth with fewer restrictions. Our health system has numerous credentialed pharmacists across multiple ambulatory care clinics. In this article, we highlight our process of expediting the implementation of telehealth services. This process included obtaining authorization for the credentialed pharmacists to provide telehealth services, completion of training modules, implementation of new technology platforms, development of new workflows, and utilization of resources for providers and patients to facilitate successful completion of telehealth visits. We also highlight the consent and documentation components crucially important to the telehealth visit and share some of our successes, as well as identified limitations, in providing pharmacist services via telehealth. CONCLUSION: In the setting of the COVID-19 pandemic, our institution was able to swiftly implement clinical pharmacist telehealth services for many patients, offering a safe and effective way to continue providing a high level of care. This article discusses our experience with and potential limitations of telehealth to assist other pharmacists seeking to implement and/or expand their telehealth services.

Biomarker BINGO.

This JADPRO Live session tested attendees' knowledge on biomarkers and their use in determining targeted therapy for certain tumor types, key assays used to measure common biomarkers, and guideline-endorsed biomarker testing recommendations.

2018-2019 Drug Updates in Hematologic Malignancies.

Lauren Held, PharmD, BCOP, updated attendees on the FDA-approved therapies for initial or expanded indications for hematologic malignancies across the past year, as well as their supporting clinical trial data and best practices for safe and effective dosing and administration, drug monitoring, and adverse event management.

A Phase I study of arsenic trioxide (Trisenox), ascorbic acid, and bortezomib (Velcade) combination therapy in patients with relapsed/refractory multiple myeloma.

PURPOSE: This Phase I study assessed the feasibility of concomitant arsenic trioxide (ATO), ascorbic acid (AA), and bortezomib (Velcade™) (AAV) for patients with relapsed/refractory multiple myeloma. EXPERIMENTAL DESIGN: ATO (0.25 mg/kg) and AA (1 g) were given with an escalating dose of bortezomib (1 mg/m(2) or 1.3 mg/m(2) IV bolus on days 1 and 8 of a 21-day cycle). RESULTS: Ten patients (median age 62 years), with a median of 3 prior regimens, were enrolled. Four (40%) patients achieved clinical benefit, with one patient achieving a durable partial response. No formal DLTs were encountered. CONCLUSION: AAV combination was feasible and demonstrated some benefits in this heavily pretreated population.