Subcutaneous Bortezomib Associated With Reduced Incidence of Peripheral Neuropathy in Multiple Myeloma

Subcutaneous (SC) bortezomib (Velcade; Takeda Pharmaceuticals) may be associated with a lower incidence of peripheral neuropathy, infection, and dyspepsia compared with intravenous (IV) injection, according to findings from an observational study. The data, published in Hematology, further support previous investigations showing how administration route and dosage can impact adverse effects (AEs) during treatment with bortezomib.¹

Patient self-administering subcutaneous injection | Image Credit: © - stock.adobe.commanusapon

Bortezomib

Bortezomib was the first FDA-approved proteasome inhibitor indicated for the treatment of multiple myeloma (MM) in 2003 and remains a cornerstone agent in the treatment landscape to this day. It holds a critical role in the first-line treatment of MM, typically in combination with other agents such as lenalidomide (Revlimid; Bristol Myers Squibb) and dexamethasone—known as VRd. Despite bortezomib’s widespread use across disease stages and within various combination therapies, bortezomib is associated with multiple AEs including neuropathy, infection, gastrointestinal reactions, and hematological toxicities. These can negatively impact treatment outcomes, leading to impaired patient compliance and the potential need for treatment discontinuation.^1,2

The Study

The observational study included 155 patients with MM (mean age 60.86 ± 9.35; 58.06% male) with stage 1 (n = 10; 6.49%), 2 (n = 14; 9.09%), or 3 (n = 130; 84.42%) disease who received either SC (n = 85; 54.84%) or IV bortezomib (n = 70; 45.16%). Bortezomib was administered in 2 doses: 1.0 mg/ m2 (n = 69; 44.52%) and 1.3 mg/m2 (n = 86; 55.48%).¹

The authors first conducted a cross-sectional analysis using univariate methods to examine peripheral neuropathy, infection, dyspepsia, constipation, and related clinical data in patients with MM. Then, they performed multivariate linear regression and smooth curve fitting to analyze how bortezomib administration route, dosage, and disease stage relate to the aforementioned AEs across 4 induction courses.¹

Key Findings

The authors had 4 key takeaways from the study. First, they identified that the administration route (PPN = 0.0324, P infection = 0.0001, P dyspepsia = 0.00001, P constipation = 0.9235), dose (PPN = 0.185, P infection = 0.0427, P dyspepsia = 0.1405, P constipation = 0.2633), and disease staging (PPN = 0.005, P infection = 0.0985, P dyspepsia = 0.0041, P constipation = 0.9087) had a strong correlation with the incidence of peripheral neuropathy, infection, dyspepsia, and constipation.¹

Second, SC injection of bortezomib was associated with reduced AEs compared with IV injection, with no significant effect on its efficacy. Multivariate-adjusted linear regression analysis showed that peripheral neuropathy (β = −0.27, P = 0.0457), infection (β = −0.65, P = 0.0003), and dyspepsia (β = −0.62, P < .0001) were lower in the SC arm than the IV arm.¹

Third, patients with stage 3 disease had a higher level of peripheral neuropathy than patients with stage 1 disease (β = 0.53, 95%CI [0.02, 1.05], P = 0.0443). Fourth, reducing the dose of bortezomib increased the level of infection among patients with MM but did not affect its efficacy (β = −0.39, 95%CI [−0.76, −0.01], P = 0.0437).¹

“Here, we found that MM patients in stage 3 suffered heavier BIPN [bortezomib-induced peripheral neuropathy] than MM patients in disease stage 1,” the authors concluded. “This finding highlighted that the tumor burden at the initial onset of MM patients had a particular influence on peripheral neuropathy after bortezomib treatment. It prompts us to observe the level of PN [peripheral neuropathy] exacerbation in one of the treatments of patients with stage 3 MM.”¹

REFERENCES

1. Dong M, Han X, He J, et al. Determining the factors affecting bortezomib’s adverse events in the treatment of newly diagnosed multiple myeloma. Hematology. September 1, 2025. doi: 10.1080/16078454.2025.2548069

2. FDA Approves Velcade. Drugs.com. May 13, 2003. Accessed September 2, 2025. https://www.drugs.com/newdrugs/fda-approves-velcade-bortezomib-relapsed-refractory-multiple-myeloma-274.html