(127) Impact of 1.3 mg/m2 versus 1.5 mg/m2 Weekly Bortezomib Dosing within Bortezomib-Lenalidomide-Dexamethasone (VRd) Front-line Induction Therapy for Multiple Myeloma

Poster Abstract:

Background: The use of combination triplet therapy with immunomodulatory agents, proteasome inhibitors, and dexamethasone for the treatment of multiple myeloma has yielded increased rates of complete response and improved outcomes, amongst transplant eligible and transplant ineligible patients compared to doublet therapy. Although bortezomib, lenalidomide, and dexamethasone (VRd) improved efficacy outcomes compared to lenalidomide and dexamethasone (Rd), there were significantly higher rates of adverse effects leading to bortezomib dose reductions and, at times, early termination of treatment. As the standard dosing schedule of bortezomib in these trials was 1.3 mg/m2 twice weekly, clinicians have since sought to mitigate adverse effects while maintaining efficacy by reducing the bortezomib dosing to once weekly. This research project seeks to answer a question that has not yet been identified in the literature: whether there is a difference in response rates between 1.3 mg/m2 and 1.5 mg/m2 bortezomib doses within the weekly VRd regimen in the first-line setting for the treatment of multiple myeloma.

Objectives: The primary objective of this study is to compare the overall response rate of bortezomib 1.3 mg/m2 versus 1.5 mg/m2 weekly in multiple myeloma patients that were treated with VRD as first-line induction therapy. Secondary objectives include analyzing the incidence of all-grade peripheral neuropathy, as well as secondary efficacy outcomes including: time to best response, progression free survival, overall survival, minimal residual disease, and the percentage of patients that proceeded to transplant.

Methods: This study is a retrospective chart review performed across outpatient clinics within a single health system. All patients that received VRd for the first-line induction treatment of multiple myeloma during the study period of 7/1/2016 through 8/1/2023 will be screened for inclusion. Diagnosis of multiple myeloma will be in accordance with the International Myeloma Working Group diagnostic criteria. Included patients will have received VRd with bortezomib 1.3 mg/m2 or 1.5 mg/m2 subcutaneously weekly. Patients will be excluded if they received VRd in second or later-line therapy, other chemotherapeutic agents in addition to the VRd regimen, or other dosing bortezomib schedules within the VRd regimen. The primary objective will be analyzed utilizing Chi-Squared test. Secondary objectives will be analyzed accordingly by Kaplan-Meier or Chi-Squared test.

Results/

Conclusion: Data collection is ongoing.

References (must also be included in final poster): 1. Roussel M, Lauwers-Cances V, Robillard N, . et al. Frontline transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: A phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014; 32( 25): 2712– 2717.

2. Richardson PG, Weller E, Lonial S, . et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010; 116( 5): 679– 686.

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4. Cook J, et al. Outcomes with different administration schedules of bortezomib in bortezomib, lenalidomide and dexamethasone (VRd) as first-line therapy in multiple myeloma. Am J Hematol. 2021 Mar 1;96(3):330-337

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7. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-e346. doi:10.1016/S1470-2045(16)30206-6