(143) Impact of weekly bortezomib versus twice weekly bortezomib on rates of peripheral neuropathy in combination with lenalidomide, dexamethasone and daratumumab

Poster Abstract: Daratumumab in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) is commonly used as a frontline treatment for multiple myeloma. This combination regimen is based on results from the phase II GRIFFIN and phase III PERSEUS trials. In these trials, bortezomib, a proteasome inhibitor, was administered twice weekly on days 1, 4, 8 and 11 of each 21-day cycle. A common side effect of bortezomib is peripheral neuropathy. All grade peripheral neuropathy was seen in 59.6-72.5% of patients in the GRIFFIN trial and 51.6-53.6% in the PERSEUS trial. Given the significant morbidity of peripheral neuropathy seen with twice weekly bortezomib, smaller studies have evaluated giving once weekly bortezomib in a 28-day regimen. The 28-day cycle still administers the same total cycle dose of bortezomib as the 21-day cycle. These studies have shown similar efficacy when cross-compared to the GRIFFIN and PERSEUS trial but with lower rates of peripheral neuropathy. At Yale New Haven Health System (YNHHS) the practice of giving weekly versus twice weekly bortezomib in the D-VRd regimen is variable and provider specific. The rates of peripheral neuropathy with weekly versus twice weekly bortezomib has not been compared head-to-head in a clinical trial. This study will add additional literature to the tolerability of weekly versus twice weekly bortezomib in patients receiving D-VRd and help standardize practice at YNHHS.

The primary objective is to assess the rates of peripheral neuropathy in patients with multiple myeloma receiving D-VRd in once weekly compared to twice weekly. The secondary objectives include number of bortezomib dose reductions and/or dose discontinuations during therapy due to peripheral neuropathy, rate of peripheral neuropathy stratified by grade and number of anti-neuropathic pain agents started during therapy.

This is a single-center, retrospective cohort study performed on eligible patients treated at YNHHS from January 1, 2017, to November 1, 2023. Patients ≥18 years of age with a diagnosis of multiple myeloma who were treated with D-VRd and received at least two doses of bortezomib were included. Patients were excluded if they had a diagnosis of peripheral neuropathy prior to starting D-VRd, received anti-neuropathic medications prior to D-VRd treatment, if they had received bortezomib in a regimen prior to D-VRd or if they switched from a twice weekly regimen to a once weekly regimen for reasons other than peripheral neuropathy.

Results, Discussion and Conclusion in progress.

References (must also be included in final poster): 1. Bortezomib. Package Insert. Takeda Pharmaceuticals; 2022.
2. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288
3. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. Published online 2023. doi:10.1056/NEJMoa2312054
4. Cook J, Johnson I, Higgins A, 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;96(3):330-337. doi:10.1002/ajh.26074