Pharmacist perspectives on emerging T cell-engaging bispecific therapies in cancer therapeutics.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To summarize the pharmacology, efficacy, safety, dosing, administration, and pharmacist perspectives related to operationalization of new and emerging bispecific therapies indicated for the treatment of various cancers. SUMMARY: In recent years, there have been significant advancements in the expansion of immunotherapeutics in the treatment of various malignancies. Bispecific T cell-engaging therapies represent an emerging therapeutic drug class for the treatment of cancer. These therapies are unique antibody constructs that bind simultaneously to 2 targets, a tumor-specific antigen and CD3 on T cells, to elicit an immune response. Recently, several bispecific therapies have been approved, including epcoritamab, glofitamab, mosunetuzumab, tebentafusp, and teclistamab. Epcoritamab and glofitamab have been approved for diffuse large B cell lymphoma, while mosunetuzumab, tebentafusp, and teclistamab have been approved for follicular lymphoma, uveal melanoma, and multiple myeloma, respectively. As a result of their mechanism of action, the approved bispecific therapies have the potential to cause cytokine release syndrome, and, along with this, they all have unique and specific monitoring parameters and operational considerations that require clinician awareness when administering these therapies. Such operational challenges include within-patient dose escalations at therapy initiation, hospitalization for monitoring, and various pharmacological strategies for prophylaxis of cytokine release syndrome. CONCLUSION: Bispecific therapies have continued to evolve the therapeutic landscape of cancer, primarily in hematological malignancies. Health-system pharmacists have the opportunity to play a key role in the operationalization and management of this new and emerging drug class.

Short term safety of coronavirus disease 2019 vaccines in patients with solid tumors receiving systemic therapy.

BACKGROUND: There are currently three coronavirus disease 2019 (COVID-19) vaccines approved by the United States Food and Drug Administration to prevent coronavirus infection. However, robust data are unavailable on the adverse events of the vaccines in patients with solid tumor malignancies undergoing systemic therapies. AIM: To evaluate the safety of COVID-19 vaccines in patients with solid tumors undergoing systemic therapies. METHODS: The study included patients with solid tumors treated in an academic tertiary care center who received COVID-19 vaccination between January 1, 2021 and August 15, 2021, while undergoing systemic therapy. Electronic medical records were accessed to collect information on patient characteristics, systemic therapies, type of vaccine received, and adverse effects associated with the vaccine administration. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: The analysis included 210 patients; the median age was 70 years, and 51% of patients were female. The most common chemotherapy, immunotherapy, and targeted therapy administered were taxane-based regimens 14.2% (30/210), anti-programmed death 1 (PD-1) agents 22.8% (48/210), and antiangiogenic agents 7.1% (15/210), respectively. The most common cancers were gastrointestinal 43.8% (92/210), thoracic 30.4% (64/210), and genitourinary 17.6% (37/210). Patients received the following vaccines: 2 doses of BNT162b2 by Pfizer 52% (110/210), 2 doses of mRNA-1273 by Moderna 42% (89/210), and 1 dose of JNJ-78436735 by Johnson & Johnson 5% (11/210). At least 1 AE attributable to the vaccine was observed in 37 patients 17.6% (37/210). The total number of AEs attributable to vaccines was 62: Fifty-three grade 1 and nine grade 2. Most adverse events occurred after the second dose 59.7% (37/62). The most frequent grade 1 AEs included fatigue 17% (9/53), fever 15% (8/53), injection site reaction 13.2% (7/53), and chills 9.4% (5/53). The most frequent grade 2 AEs were fatigue 33.3% (3/9) and generalized weakness 22.2% (2/9). Therapy was delayed by 2 wk because of the AEs possibly related to vaccine administration in 3 patients 1.4% (3/210). CONCLUSION: The present study demonstrates that the adverse events associated with COVID-19 vaccination are infrequent, mild, and rarely delay treatment in patients with solid tumors receiving systemic therapies.

Feasibility of a pharmacist-led symptom monitoring and management intervention to improve breast cancer endocrine therapy adherence.

BACKGROUND: Adjuvant endocrine therapy (AET) for breast cancer reduces mortality, but one-third to one-half of patients discontinue it early or are nonadherent. OBJECTIVE: We developed a pilot single-site study of patients with evidence of early nonadherence to AET to assess the feasibility of a novel, clinical pharmacist-led intervention targeting symptom and medication management. METHODS: Patients with prescription fill records showing nonadherence were enrolled in a single-arm feasibility study. Automated reminders were sent by e-mail or text with a link to symptom monitoring assessments weekly for 1 month and monthly until 6 months. Clinical oncology pharmacists used guideline-based symptom management and other medication management tools to support adherence and ameliorate symptoms reported on the assessments. Patient-reported outcome assessments included physical, mental, and social health domains and self-efficacy to manage symptoms and medications. Feasibility outcomes included completion of symptom reports and pharmacist recommendations. RESULTS: Of 19 participants who were nonadherent who enrolled and completed initial assessments, 18 completed all final study procedures, with 14 completing all assessments and no patient missing more than 3 assessments. All 18 participants reported at least one of 3 symptom types, and the majority reported attempting pharmacist recommendations. Patient-reported measures of physical, mental, and social health and self-efficacy improved, and 44% of the patients became adherent. CONCLUSION: An intervention using pharmacists in an oncology practice to systematically monitor and manage symptoms shows promise to reduce symptoms, enhance support and self-efficacy, and improve adherence to AET.

New and emerging pharmacotherapies for the management of multiple myeloma.

PURPOSE: The pharmacology, efficacy, safety, and dosing/administration of new and emerging therapies for the treatment of multiple myeloma are summarized. SUMMARY: There have been significant advancements in the treatment of multiple myeloma in recent years, with an expansion of available drug therapies. Newer therapies for multiple myeloma include the anti-CD38 monoclonal antibodies daratumumab and isatuximab, the exportin 1 inhibitor selinexor, the anti-B-cell maturation antigen (BCMA) antibody-drug conjugate belantamab mafodotin, and the chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel. These agents have unique toxicity profiles, specific monitoring parameters, and operational considerations that clinicians treating multiple myeloma should be aware of. There is likely to be continued rapid expansion of new agents for patients with multiple myeloma, as there are many novel investigational agents in the drug development pipeline, such as bispecific antibodies and additional CAR T-cell therapies. CONCLUSION: Several therapeutic agents have been recently approved by the Food and Drug Administration for the treatment of multiple myeloma. There are many novel agents in the pipeline, including bispecific antibodies and CAR T-cell therapies that have the potential to continue to change the treatment landscape of multiple myeloma.

TAS-102: A resurrected novel Fluoropyrimidine with expanding role in the treatment of gastrointestinal malignancies.

TAS-102 is an orally administered fixed-dose formulation consisting of trifluorothymidine (TFT), a fluoropyrimidine antimetabolite, and tipiracil (TPI), an inhibitor of thymidine phosphorylase (TP) that prevents rapid degradation of TFT and ensures its bioavailability. The novelty of TAS-102 lies in its antitumor activity against 5-fluorouracil (5-FU) resistant tumors, demonstrated both in the in vitro models and xenografts. The cytotoxic activity of TFT relies primarily on extensive incorporation of the TFT metabolite into the cellular DNA inducing DNA dysfunction and cell death. In contrast, 5-fluorouracil (5-FU) interferes with DNA biosynthesis by inhibiting thymidylate synthase(TS), which partly explains the absence of cross-resistance between TAS-102 and 5-FU. TAS-102 is currently approved in the third-line setting for patients with metastatic colorectal and gastric cancer based on phase III randomized clinical trial data confirming an overall survival benefit with TAS-102. The preliminary data from recently reported studies suggest a potential expanding role of TAS-102 in a variety of gastrointestinal (GI) cancers. The current article presents an overview of the pharmacology, clinical development of TAS-102, and its emerging role in the treatment of GI cancers. In addition, we discussed the rationale underlying the ongoing clinical trials investigating various combinations of TAS-102 with other anticancer agents, including targeted therapies, in a wide range of GI tumors.

Evaluation of the Pharmacokinetics and Efficacy of a Busulfan Test Dose in Adult Patients Undergoing Myeloablative Hematopoietic Cell Transplantation.

Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose. An observational study was completed to evaluate the effects of a busulfan test dose of 0.9 mg/kg administered before the start of a myeloablative intravenous busulfan-based conditioning regimen. Sixty adult patients who received a busulfan conditioning regimen were reviewed, including 30 patients prior to the implementation of the busulfan test dose (pretest dose group) and 30 patients who received the busulfan test dose (posttest dose group). The primary objective was a pharmacokinetic evaluation of the percentage of patients who achieved the desired steady-state goal using the test dose strategy. The safety and efficacy of the busulfan test dose were evaluated as well. The average busulfan steady-state level after the first dose of the conditioning regimen was significantly lower in the pre-test dose group compared with the post-test dose group (660 ng/mL versus 879.9 ng/mL; P < 0.001). Compared with the post-test dose group, significantly fewer patients in the pre-test dose group were within 10% of the busulfan steady-state goal (10% versus 73.3%; P < 0.001) or within 5% of the goal (0% versus 53%; P < 0.001). Requirements for parenteral nutrition and/or patient-controlled analgesia owing to mucositis and rates of veno-occlusive disease were not significantly different between the pre-test dose group and the post-test dose group. The rates of disease relapse, mortality, and acute graft-versus-host disease were similar in the two groups. A pretransplantation busulfan test dose of 0.9 mg/kg improved the patients' ability to reach therapeutic busulfan target levels after the first conditioning dose and resulted in fewer adjustments during conditioning. The use of a busulfan test dose did not significantly increase patients' risk of mucositis or other safety outcomes.

Pharmacist collaborative practice agreement for the management of anemia in malignant disease with erythropoiesis-stimulating agents.

PURPOSE: Erythropoiesis-stimulating agents (ESAs) reduce transfusions and increase hemoglobin levels in patients with anemia of malignant disease. A medication guideline and pharmacist collaborative practice agreement (CPA) were developed and implemented to standardize ESA prescribing workflow. The use of ESAs in malignant diseases, in accordance with institutional guidelines, was evaluated to ensure safe and effacious use. METHODS: An observational study was conducted on all ESA doses given throughout a health system's cancer clinics prior to and after implementation of an ESA guideline and pharmacist CPA. The primary outcome measured was ESA therapy initiated in accordance with guidelines before and after the intervention. Secondary outcomes evaluated were nurse and pharmacist satisfaction, vitals recorded prior to dose, and transfusion rates in patients receiving ESA therapy before and after the intervention. RESULTS: In the pre-implementation group, criteria for initiation were not met by any of the 39 patients; prior to therapy, 5.1 % of patients had not had hemoglobin drawn, 23 % of patients had no iron studies completed, and 29.4 % of myelodysplastic syndrome (MDS) patients had no erythropoietin levels drawn. In the post-implementation group, prior to therapy, all patients had hemoglobin levels drawn, 16.67 % did not have iron studies completed, and all MDS patients had erythropoietin levels drawn appropriately. Chemotherapy-induced anemia (CIA) patients in the pre-implementation group had 71.4 % compliance with receiving chemotherapy within 8 weeks of ESA dose, and the post-implementation group had 100 % compliance. CONCLUSION: An ESA guideline and pharmacist CPA aligned prescribing practices with the NCCN and ASCO guidelines and improved staff satisfaction.

Medication reconciliation at an academic medical center: implementation of a comprehensive program from admission to discharge.

PURPOSE: The implementation of a comprehensive medication reconciliation program to reduce errors in admission and discharge medication orders at an academic medical center is described. SUMMARY: A multidisciplinary team was formed to assess the current process of obtaining medication histories and to develop a new workflow for the pharmacist to obtain and reconcile medication histories. Pharmacists received intensive training on the new workflow, policies, and procedures. Hospitalwide multidisciplinary education was provided, and the new process was introduced in November 2005. Every inpatient admitted to the hospital has a complete and comprehensive home medication history interview conducted by a pharmacist or designee (pharmacy student or intern with subsequent verification by a pharmacist) within 24 hours of arrival. All components of the medication history are documented utilizing an integrated electronic medical record (EMR) medication documentation tool. Development of the discharge medication reconciliation program began in fall 2006. A discharge medication reconciliation report form was created through the EMR to improve the accuracy of the discharge medication orders. The form provides physicians with complete, accurate medication information and decreases the risk for transcription errors. Finally, a discharge medication report was developed for patients to take home. Analysis of the discharge reconciliation process revealed that medication errors were reduced from 90% to 47% on the surgical unit (95% confidence interval [CI], 42-53%; p = 0.000) and from 57% to 33% on the medicine unit (95% CI, 28-38%; p = 0.000). CONCLUSION: A pharmacy-driven multidisciplinary admission history and medication reconciliation process has reduced medication errors in an academic medical center.