Bortezomib dosing once a week safer than twice a week: Study

Reduced regimen linked to fewer side effects, such as peripheral neuropathy

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Once-weekly induction therapy with bortezomib is as efficient as the standard two times a week dosing in people newly diagnosed with multiple myeloma, a large retrospective real-world study suggests.

No differences were seen between both regimens regarding survival overall and the time patients lived without disease progression, but the once a week schedule was linked to fewer side effects, namely peripheral neuropathy, wherein the nerves outside the brain and spinal cord are damaged.

The findings support “the incorporation of once-weekly bortezomib into standard-of-care regimens for newly diagnosed patients with MM [multiple myeloma],” the researchers wrote in “Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis,” which was published in the Blood Cancer Journal.

In multiple myeloma, the uncontrolled growth of plasma cells, a type of immune cell, lead to plasma cell tumors inside and/or outside bones.

A proteasome inhibitor approved for myeloma, bortezomib prevents myeloma cells from breaking down their abnormal or damaged cellular components, leading to toxicity and cell death. It’s administered as injections under the skin, that is, subcutaneously, or into the vein (intravenously). Bortezomib is sold as Velcade and as generics.

“Induction regimens for MM commonly include … bortezomib, which has typically been administered twice per week in 21-day or 28-day cycles,” the researchers wrote. However, its use is linked with peripheral neuropathy that can cause symptoms of numbness and painful burning, tingling, or pricking sensations.

Mounting evidence from single-center studies and secondary analyses of Phase 3 clinical trials suggests once-weekly bortezomib “has comparable efficacy with less [peripheral neuropathy] as compared to twice-weekly bortezomib,” the researchers wrote.

In fact, induction therapy based on once-weekly bortezomib has been widely adopted in real-world clinical practice, but most clinical trial protocols still use the twice-weekly regimen.

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Once a week, twice a week bortezomib dosing regimen

Here, a team led by researchers at the UT Southwestern Medical Center, Dallas, Texas sought to “assess the prevalence, effectiveness, and toxicities of once-weekly versus twice-weekly bortezomib dosing regimens in a broader and more contemporary” group of adults, 18-70 years, who were newly diagnosed with myeloma. They retrospectively analyzed real-world data from 2,497 patients (mean age at diagnosis, 62; 44.6% women) who were registered in the U.S. Flatiron Health electronic health record database.

All were diagnosed between 2017 and 2022 and had received their first-line induction therapy with bortezomib. About half (49.7%) were non-Latino whites, 22.1% were non-Latino Black, and 8.5% were Latino. Bortezomib was administered twice a week to 910 patients (36.4%) and once a week to 1,587 patients (63.6%).

Compared with patients treated with twice-weekly bortezomib, those on the once-weekly regimen were significantly less likely to be Hispanic/Latinos (11.2% vs. 6.9%) and more likely to have been treated at academic centers (18.7% vs. 16.9%).

A significantly higher proportion of patients on the once-weekly regimen had two or more evaluations using the Eastern Cooperative Oncology Group (ECOG) performance status, a measure of a cancer patient’s daily functioning (15.1% vs. 11.5%). Bortezomib was more frequently administered subcutaneously in the once-weekly group (96.3% vs. 92.4%). Other demographic and clinical characteristics were generally similar between the groups.

The frequency of once-weekly bortezomib increased over time, from 57.7% in 2017 to 73.1% in 2022, which “may reflect a growing consensus in the field that once-weekly bortezomib constitutes a standard-of-care regimen for MM,” the researchers wrote.

Two or more ECOG performance visits and a more recent diagnosis were significantly associated with higher odds of bortezomib being given once a week, statistical analyses showed. But the once-weekly regimen was significantly less common among Hispanic/Latino patients than non-Latino white patients, and among those dosed intravenously than subcutaneously.

Outcomes with once-weekly dosing regimen

No significant differences were seen between bortezomib once a week and twice a week regarding progression-free survival (PFS), the time that a patient lives without signs of cancer progression (median 37.2 vs. 39.6 months).

There also were no significant group differences with median overall survival. This measure wasn’t reached in any group, meaning most patients were still alive after a median follow-up of 27.1 months.

Consistent with past studies, peripheral neuropathy was significantly more common in those given bortezomib twice a week (34.7% vs 18.5%).

“This represents the largest and the most extensive real-world analysis of bortezomib dosing to date,” wrote the researchers, who said the results further point out that “once-weekly bortezomib is associated with equivalent outcomes and a more favorable side-effect profile compared to twice-weekly dosing.” They said dosing once a week also reduces the “clinical burden of care by reducing visit frequency” and may be more “cost-effective.”