The TOURMALINE-MM1 study: subgroup analysis via prior therapy

A subgroup analysis of the TOURMALINE-MM1 was published on 27^th July 2017 in Haematologica. The study was led by Maria Victoria Mateos, from the Hospital Universitario de Salamanca, Spain, and a member of the MM Hub Steering Committee. The authors investigated the effect of previous therapies on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-lenalidomide-dexamethasone (placebo-Rd), in patients with Relapsed/Refractory Multiple Myeloma (RRMM). A summary of the TOURMALINE-MM1 study key highlights and results were reported in a previous MM Hub article.

Study Highlights

• Patients (pts) included in the study = 722 pts
• Subgroups analyzed:
  • Type of previous therapy: proteasome inhibitor (PI) (n = 503) and immunomodulatory drug (IMiD) (n = 397)
  • Number of previous therapies: 1 (n = 425) vs 2 or 3 (n =297)

Key Findings

• Median follow-up = 15 months
• Median Progression Free Survival (PFS) showed better clinical benefit with ixazomib-Rd vs placebo-Rd regardless of previous therapy type:
  • PI-exposed pts = 18.4 vs 6 months (HR = 0.739)
  • PI-naïve pts = not reached vs 7 months (HR = 0.749)
  • IMiD-exposed pts = not reached vs 5 months (HR = 0.744)
  • IMiD-naïve pts = 20.6 vs 6 months (HR = 0.700)
• Median Time To Progression (TTP) was also longer with ixazomib-Rd vs placebo-Rd regardless of previous therapy type:
  • PI-exposed pts = 18.5 vs 9 months (HR = 0.702, 95% CI 0.526, 0.936)
  • PI-naïve pts = not estimable vs 5 months (HR = 0.741, 95% CI 0.456, 1.203)
  • IMiD-exposed pts = not estimable vs 3 months (HR = 0.727, 95% CI 0.515, 1.026)
  • IMiD-drug-naïve pts = 20.6 vs 6 months (HR = 0.651, 95% CI 0.449, 0.945)
• PFS and TTP was prolonged for ixazomib-Rd vs placebo-Rd in pts with 1, 2 or 3 prior therapies
  • PFS 1 vs 2 or 3 prior therapies = HR = 0.88 (95% CI: 0.65–1.20) vs 58 (95% CI: 0.40–0.84)
  • TTP 1 vs 2 or 3 prior therapies = HR = 0.842 (95% CI 0.614, 1.156) vs 550 (95% CI 0.370, 0.819)

Safety

• Median follow-up = 23 months
• Toxicity findings were similar across all subgroups
• Higher rates of grade ≥3 Adverse Events (AE) and serious AEs were seen in the placebo-Rd subgroup and in pts who had 2 or 3 previous therapies

Conclusion

This efficacy study showed that PFS and TTP was prolonged with ixazomib-Rd treatment, but that there was no specific correlation with prior treatment with a PI, IMiD or the number of previous treatments received. Safety profiles showed no additional toxicity concerns amongst the subgroups. The study subgroup analysis further confirmed the positive results of using ixazomib-Rd in RRMM therapy as demonstrated in the TOURMALINE-MM1 study.