KEY TAKEAWAYS
- The Phase 3 trial assessed the efficacy of ixazomib in multiple myeloma patients.
- The primary aim was to determine the progression-free survival benefit of ixazomib in combination with lenalidomide-dexamethasone compared to a placebo.
- A total of 2247 patients with multiple myeloma were assessed in the trial to determine the efficacy of ixazomib.
- Ixazomib-based therapy demonstrated a progression-free survival benefit compared to placebo-based therapy in high-risk and standard-risk patients.
- Patients with t(4;14) and amp1q21 chromosomal abnormalities exhibited the most significant benefit.
- Proteasome inhibitors like ixazomib can potentially improve outcomes for multiple myeloma patients with high-risk cytogenetic abnormalities.
Certain cytogenetic abnormalities (CAs) have been observed to be linked with unfavorable prognosis in patients diagnosed with multiple myeloma (MM). However, proteasome inhibitors have demonstrated the potential to improve patients’ outcomes with high-risk CAs. A total of 2247 patients with multiple myeloma were assessed in the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to determine the progression-free survival benefit of ixazomib in combination with lenalidomide-dexamethasone (Rd) compared to placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib compared to placebo (TOURMALINE-MM3/-MM4) in high-risk chromosomal abnormalities. Following a median follow-up of 25.6 months, the hazard ratio (HR) for progression-free survival (PFS) between ixazomib-based therapy and placebo-based therapy for high-risk patients was 0.74 (95% confidence interval [CI]: 0.59-0.93; median PFS [mPFS] 17.8 vs 13.2 months).
The HR for complementary standard-risk patients was also 0.70 (95% CI: 0.62-0.80; mPFS 26.3 vs 17.6 months). The hazard ratio (HR) for high-risk patients who underwent expansion was 0.75 (95% CI: 0.64-0.87; median progression-free survival (mPFS) 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59-0.85; mPFS 36.1 vs 21.4 months) for standard-risk patients who received complementary treatment. The hazard ratio (HR) for progression-free survival (PFS) with ixazomib-based therapy as compared to placebo-based therapy was 0.68 in patients with t(4;14) (95% confidence interval [CI]: 0.48-0.96; median PFS [mPFS] 22.4 vs 13.2 months), and 0.77 for patients with amp1q21 (95% CI: 0.63-0.93; mPFS 18.8 vs 14.5 months). Ixazomib-based therapy demonstrated a PFS benefit compared to placebo-based therapy irrespective of cytogenetic status. The patients with t(4;14) and amp1q21 exhibited the most significant benefit.
Source:https://pubmed.ncbi.nlm.nih.gov/36631458/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT01564537
Chng WJ, Lonial S, Morgan GJ, Iida S, Moreau P, Kumar SK, Twumasi-Ankrah P, Villarreal M, Dash AB, Vorog A, Zhang X, Suryanarayan K, Labotka R, Dimopoulos MA, Rajkumar SV. A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma. Blood Cancer J. 2023 Jan 12;13(1):14. doi 10.1038/s41408-022-00768-5. PMID: 36631458; PMCID: PMC9834310.
