Evaluation of Pharmacist-Managed Thiopurine-Based Leukemia Maintenance Service Via a Collaborative Practice Agreement

Introduction: Maintenance therapy (MNT) plays a critical role preventing relapse in the treatment of acute lymphoblastic leukemia (ALL) and acute promyelocytic leukemia (APL). During MNT, patients receive mercaptopurine (6MP) and methotrexate (MTX) along with other agents such as vincristine, tretinoin, steroids and intrathecal chemotherapy. Due to inter- and intra-patient variability in pharmacodynamics and kinetics, 6MP and MTX are dose adjusted to a target absolute neutrophil count (ANC) while monitoring platelet counts and liver function tests (LFTs). Pharmacists are uniquely positioned to manage the complex MNT and deliver efficient and cost-effective care. In Utah specifically, pharmacists have the opportunity to participate in collaborative practice agreements (CPA) with practitioners for the purpose of drug therapy management. We developed a pilot program with a pharmacist led CPA for the management of ALL and APL patients in the MNT phase.

Methods: The CPA was approved through the local Pharmacy and Therapeutics Committee on 10/13/2023. A goal was to assess the time saved for the hematologist, advanced practice clinician, and nurses. ALL and APL patients starting MNT were enrolled at the time of initiation of MNT phase. At the time of initiation, patients were provided an in-person 20-minute education visit which included printed material about each drug and a personalized treatment calendar. Follow-up visits for laboratory monitoring were assigned 10 minutes of time spared (5 minutes for review of labs and 5 minutes for communication with the patient). Thiopurine methyltransferase (TPMT) and nudix (nucleoside diphosphate linked moiety X)-type motif 15 (NUDT15) genotyping was performed on all patients. Based on the genotype data, the pharmacist determined the initial dose and schedule and wrote prescriptions. As patients started the MNT phase of treatment, follow up laboratory studies were performed at scheduled intervals determined by the pharmacist. Laboratory results and dose changes were discussed with the patient via MyChart, phone, or in person. A note was documented in the chart with results of laboratory data and treatment plan including dose adjustments and further monitoring.

Results: As of July 10, 2024 (8 months of practicing under the CPA), 8 patients with ALL and 2 patients with APL received MNT under the pharmacist's care via this CPA. The median age was 32 years (range 19 - 67), one patient had *3A/*1 TPMT genotype (intermediate metabolizer), the rest were *1/*1 (normal metabolizer). The 2 APL patients were receiving MNT per APML4 for high-risk disease. Four patients with ALL were receiving POMP MNT following HyperCVAD-based intensive therapy, and 4 patients were receiving Course V per the CALGB 10403 protocol (a pediatric-inspired regimen for Adolescent and Young Adult patients). Each patient had their labs drawn at intervals ranging from once weekly to once monthly, depending on their needs for monitoring and dose modification. Six initial visits with dosing determination, prescription writing, and patient education were performed to save a total of 120 minutes of provider and nursing time. A total of 133 follow-up visits have been performed, saving 1,330 minutes of provider and nursing time. In total thus far, pharmacists practicing under this CPA have saved a total of 24 hours of provider and nursing time or 3 hours of time per month. Furthermore, pharmacists have recommended 17 dose adjustments and 15 interruptions. Zero patients were hospitalized for neutropenic fever. Two patients have finished MNT and 8 remain in the program.

Conclusion: Pharmacists in academic medical centers are uniquely positioned to provide care for patients with leukemia receiving this prolonged MNT requiring careful laboratory monitoring and frequent adjustments. Through this successful CPA pilot program, pharmacists have demonstrated the feasibility of providing efficient care. This framework can serve as a blueprint for other academic medical centers to follow. Moreover, this pharmacist led initiative complements the expertise of leukemia physicians and helps to reduce the burden on nursing and provider staff. This also increases pharmacist satisfaction as they are able to practice at the top of their ability. We conclude that implementation of a CPA with collaboration between pharmacists and providers to manage MNT benefits patients and the entire hematology care team.

Wagner:Jazz: Research Funding; Pfizer: Consultancy. Tantravahi:GSK: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria, Research Funding; CTI Biopharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Partnership for Health Analytic Research LLC: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria. Shami:US Patents: Patents & Royalties: holds US Patents (8,404,665; 9,005,656); National Cancer Network: Other: leadership role; JSK Therapeutics: Other: Chief Medical Officer and serves on the Board of Directors ; RJH BioSciences: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc.: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abcuro, Inc.: Other: grant; Amgen: Other: grant; Chimerix, Inc.: Other: grant.