Summary

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• This summary is based on the review of 17 systematic review(s)/meta-analysis(es). ^[1-17]
• Progression-Free Survival (PFS): In high-risk newly diagnosed multiple myeloma (NDMM) patients, bortezomib showed a median PFS of 30.4 months compared to lenalidomide's 31.7 months (hazard ratio (HR) = 0.966, 95% confidence interval (CI): 0.628-1.486, p = 0.874). Bortezomib demonstrated significant PFS improvement over placebo (HR = 0.72, 95% CI 0.55-0.95, p = 0.02). Lenalidomide-carfilzomib was superior to bortezomib-thalidomide for PFS (odds ratio (OR) range: 2.18-2.20).
• Overall Survival (OS): Bortezomib-based maintenance therapy improved OS in comparison with lenalidomide (HR = 0.71, 95% CI 0.58-0.87, p = 0.001). The lenalidomide-carfilzomib regimen showed superior OS over bortezomib-thalidomide. Additional benefits in OS were observed with bortezomib added to rituximab in diffuse large B-cell lymphoma (DLBCL).
• Response Rates: Carfilzomib (CFZ) with daratumumab achieved an overall response rates (ORR) close to 100%. Bortezomib in combination regimens also demonstrated high ORR. Bortezomib-based consolidation therapies enhanced complete response rates (CR), while acalabrutinib reported significant improvements in ORR and CR over bortezomib.
• Comparative Effectiveness: Bortezomib-based regimens generally showed comparable PFS to lenalidomide in high-risk NDMM. In comparative analyses, bortezomib regimens ranked highly for PFS and OS across different combinations and conditions, with some combinations showing superior efficacy over others.
• Bortezomib-induced peripheral neuropathy (BIPN) incidence ranged from 8.4% to 80.5% (median 37.8%), with severe neuropathy (grade 3-4) occurring in 1% to 33.2% (median 8%); reduced neuropathy incidence was observed with once-weekly versus twice-weekly dosing.
• Bortezomib-based regimens commonly resulted in hematological toxicity, cardiovascular disturbances, electrolyte imbalances, diarrhea, and thrombocytopenia, with a noted increase in grade 3 or higher adverse events, although maintenance therapy did not significantly increase severe peripheral neuropathy or secondary primary malignancies compared to placebo/thalidomide.
• Bortezomib-based regimens had increased risk for grade 3-4 neurological, gastrointestinal, and fatigue symptoms, while acalabrutinib demonstrated a comparatively better safety profile.
• High-risk NDMM patients demonstrated comparable PFS with lenalidomide and bortezomib; in refractory multiple myeloma (RRMM), pomalidomide, bortezomib, and dexamethasone ranked highest for PFS, while bortezomib-melphalan-prednisone (VMP) was effective as first-line treatment in transplant-ineligible multiple myeloma (MM); in DLBCL, adding bortezomib to rituximab improved event-free survival; specific safety considerations for hematological malignancies highlighted efficacy and improved safety with once-weekly bortezomib, while non-hematological toxicities were notable in cardiovascular subgroups.