Presenter: Eno Inyang, PharmD, BCPS, Stem Cell Transplant Clinical Pharmacy Specialist, Dana-Farber Cancer Institute
Co-Authors: Nikhil C. Munshi, MD, Department of Medical Oncology, Dana-Farber Cancer Institute; Anil Aktas-Samur, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute; Houry Leblebjian, PharmD, BCOP, Multiple Myeloma Clinical Pharmacy Specialist, Department of Pharmacy, Dana-Farber Cancer Institute
Background: Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard first-line regimen for patients with multiple myeloma who are eligible or ineligible for transplant. Based on the original APEX study data, obtaining a complete blood count (CBC) before every administration of bortezomib has been recommended. Waiting for laboratory results may add several hours to each patient visit. This can be inconvenient and costly for patients, payers, and institutions.1-10
Objectives: The primary objective was to identify patients who can receive the RVD regimen safely, without repeated laboratory tests before each bortezomib injection. Secondary objectives included evaluation of costs and appointment visit times.
Methods: A total of 89 patients were identified in this institutional review board–approved descriptive, retrospective, medical chart review of patients with multiple myeloma aged ≥18 years who received ≥3 cycles of RVD treatment from January 1, 2016, to January 31, 2020.
Results: On day 1 of each cycle (starting with cycle 2), 100% of the patients had a platelet count ≥75,000 cells/µL. Less than 10% of patients had grade ≥2 thrombocytopenia, including 2% and 0% of patients with grade 3 and 4 adverse events, respectively. The majority of patients had an absolute neutrophil count (ANC) ≥1000 cells/µL at the beginning of each cycle: 94%, 100%, and 100% in cycles 2, 3, and 4, respectively. Among the patients with an ANC ≥1000 cells/µL on the first day of cycles 2 to 4, more than 93% also had an ANC ≥1000 cells/µL on subsequent days. Grade 3 or 4 neutropenia was observed in 6.7% and 1.1% of patients, respectively. The average serum creatinine and total bilirubin for both cohorts was ≤1.2 mg/dL throughout the study for cycles 1 to 4. By only checking laboratory tests on day 1 of each cycle, we identified an average time saving of 3 to 4.5 hours and financial savings of $1542 per cycle for each patient.
Conclusion: This study demonstrates that beyond the first cycle, patients with platelets ≥75,000 cells/µL and an ANC ≥1000 cells/µL on the first day of a cycle do not need laboratory tests before each administration of bortezomib (while receiving RVD). Furthermore, a comprehensive metabolic panel does not need to be obtained before each dose of bortezomib, unless otherwise indicated, because no significant trends were seen in serum creatinine or total bilirubin levels in our study. Decreased monitoring of CBCs and reducing the number of laboratory tests will improve resource utilization, save money, and save time. This is particularly important during the COVID-19 pandemic, when reducing several hours of wait time can keep our patients and staff safer.
- APEX (Assessment of Proteasome inhibition for Extending remissions) trial: phase III randomized, multicenter, placebo-controlled trial to evaluate the efficacy and safety of bortezomib versus dexamethasone in patients with recurrent or treatment-resistant multiple myeloma. Clin Adv Hematol Oncol. 2003;1:190.
- Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-686.
- Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519-527.
- Richardson PG, Xie W, Jagannath S, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014;123:1461-1469.
- National Cancer Comprehensive Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Multiple Myeloma. Version 2.2019.
- Punke AP, Waddell JA, Solimando DA Jr. Lenalidomide, bortezomib, and dexamethasone (RVD) regimen for multiple myeloma. Hosp Pharm. 2017;52:27-32.
- Velcade (bortezomib) for injection, for subcutaneous or intravenous use [prescribing information]. Millennium Pharmaceuticals; 2019.
- Revlimid (lenalidomide) capsules, for oral use [prescribing information]. Celgene Corporation; 2019.
- Dana-Farber Cancer Institute. Dana-Farber’s charges for medical services. www.dana-farber.org/for-patients-and-families/becoming-a-patient/insurance-and-financial-information/charges-and-your-financial-responsibility/. Accessed June 2, 2020.
- Palumbo A, Bringhen S, Ludwig H, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood. 2011;118:4519-4529.