Black Patients With Multiple Myeloma May Require Additional Peripheral Neuropathy Monitoring When Receiving Bortezomib

Black Patients With Multiple Myeloma May Require Additional Peripheral Neuropathy Monitoring When Receiving Bortezomib

Black patients with multiple myeloma may be at higher risk for developing clinically actionable bortezomib (Velcade)-induced peripheral neuropathy (BIPN) and, as such, may require closer monitoring for this adverse event, according to an analysis of real-world patients that was published in JCO Oncology Practice.¹

When 141 Black patients with newly diagnosed multiple myeloma were assessed against 140 non-Black patients with the same disease, the incidence of BIPN was 46% in the Black cohort and 34% in the non-Black patients, yielding an odds ratio of 1.61 in a univariate analysis (95% CI, 1.00-2.61; P = .052) and 1.64 in a multivariable analysis (95% CI, 1.01-2.67; P = .047).

Of note, no differences in treatment discontinuation (14.3% vs 10.7%; P = .37) were reported nor in the addition of PN medications (13.6% vs 12.1%; P = .72). A slightly higher use of gabapentin was reported in the cohort of Black patients.

The route of bortezomib administration did not change the incidence of BIPN in these patients. Among those who received intravenous (IV) administration, the rate of BIPN was 40.2% (n = 41). The rate was 39.9% (n = 71) in the subcutaneous (SC) administration arm. Specifically, in the IV bortezomib subgroup, the rate of BIPN was 47% (n = 24) among Black patients and 33% (n = 17) among non-Black patients. In the SC subgroup, the rates were 45% (n = 40) vs 35% (n = 31), respectively.

All patients included in this analysis had newly diagnosed multiple myeloma and were treated with induction bortezomib, lenalidomide (Revlimid), and dexamethasone between 2007 and 2016. Patients were matched on the basis of sex, BMI, age, and route of administration. The median age at time of diagnosis was 61 years (range, 36-78 years) among the Black patients and 60 years (range, 38-82 years) among the non-Black patients. The median BMI was 28.9 vs 28.4, respectively. According to the investigators, this was consistent with the demographics among patients with multiple myeloma seen at Emory Healthcare.

“This retrospective review illustrated that Black race was an independent risk factor for the development of BIPN in patients with newly diagnosed MM receiving RVd [bortezomib, lenalidomide, and dexamethasone] therapy,” Laura F. Sun, PharmD, a fellow with Emory Healthcare and co-investigators, wrote in the study. “Clinicians should continue to vigilantly monitor Black patients on bortezomib and prescribe appropriate supportive medications and other interventions as indicated.”

Findings in Context

Black individuals are up to 3 times more likely than other races to develop multiple myeloma.² The preferred induction therapy for these individuals includes a combination of a proteasome inhibitor, an immunomodulatory agent, and a corticosteroid.

Bortezomib is a selective 26S proteosome inhibitor that functions by disrupting the major intracellular protein degradation pathway. This process results on cell cycle arrest and apoptosis. This agent is commonly used in indication therapy but is also a maintenance treatment option for patients with cytogenetically defined high-risk disease.

Bortezomib increases a patient’s risk of PN. The incidence of grade 1 or 2 BIPN events observed in clinical trials of bortezomib ranges from 40% to 70%.³ In 2012, the FDA approved a SC administration of bortezomib after a phase 3 trial (NCT00722566) demonstrated that SC administration was associated with a lower rate of PN (38%) vs IV administration (53%) while efficacy rates remained the same.⁴ Since then, SC administration has become the preferred route, and it is backed by safety, efficacy, and efficiency data, as well as patient preference. Yet, although additional studies have supported the finding that SC administration yields lower PN rates, in the phase 2 GRIFFIN trial (NCT02874742), 72% of patients experiencing any-grade PN after receiving SC bortezomib as part of their RVd induction regimen.⁵

Patients who are experiencing low-grade BIPN will often exhibit mild motor weakness and reported distal sensory loss and pain at the fingertips or toes. Management for BIPN can include opioids tricyclic antidepressants, anticonvulsants, and serotonin norepinephrine reuptake inhibitors, as well as nonsteroidal anti-inflammatory agents, vitamins, and supplements have also been documented to be beneficial. For patients who experience severe neurotoxicity, dose adjustments, or even therapy discontinuation, is often necessary.¹

Reference

1. Sun V, Maples KT, Hall KH, et al. Impact of black race on peripheral neuropathy in patients with newly diagnosed multiple myeloma receiving bortezomib induction. JCO Oncology Practice. Published online July 7, 2023. doi:10.1200/OP.22.00781
2. Röllig C, Knop S, Bornhäuser M. Multiple myeloma. Lancet. 2015;385(9983):2197-2208. doi:10.1016/S0140-6736(14)60493-1
3. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature [published correction appears in Blood. Blood. 2008;112(5):1593-1599. doi:10.1182/blood-2008-04-149385
4. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12(5):431-440. doi:10.1016/S1470-2045(11)70081-X
5. 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