TY - JOUR
T1 - A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma
AU - Chng, Wee Joo
AU - Lonial, Sagar
AU - Morgan, Gareth J.
AU - Iida, Shinsuke
AU - Moreau, Philippe
AU - Kumar, Shaji K.
AU - Twumasi-Ankrah, Philip
AU - Villarreal, Miguel
AU - Dash, Ajeeta B.
AU - Vorog, Alexander
AU - Zhang, Xiaoquan
AU - Suryanarayan, Kaveri
AU - Labotka, Richard
AU - Dimopoulos, Meletios A.
AU - Rajkumar, S. Vincent
N1 - Funding Information:
The authors would like to thank all patients and their families, as well as all investigators, for their valuable contributions to these studies. Victoria Enwemadu, PharmD, of Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA provided editorial assistance. We would also like to acknowledge Cong Li, PhD, of Takeda Development Center Americas, Inc. (TDCA), Lexington, MA who facilitated the statistical analysis. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Beth Jamieson, BSc, and Philippa Lloyd, BSc, of Ashfield MedComms, an Inizio Company, funded by Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA and complied with the Good Publication Practice (GPP) guidelines (DeTora LM, et al. Ann Intern Med 2022;175:1298–304).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs 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), and 0.70 (95% CI: 0.62–0.80; mPFS 26.3 vs 17.6 months) for complementary standard-risk patients. The HR for expanded high-risk patients was 0.75 (95% CI: 0.64–0.87; mPFS 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59–0.85; mPFS 36.1 vs 21.4 months) for complementary standard-risk patients. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4;14) (95% CI: 0.48–0.96; 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). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4;14) and amp1q21.
AB - Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs 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), and 0.70 (95% CI: 0.62–0.80; mPFS 26.3 vs 17.6 months) for complementary standard-risk patients. The HR for expanded high-risk patients was 0.75 (95% CI: 0.64–0.87; mPFS 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59–0.85; mPFS 36.1 vs 21.4 months) for complementary standard-risk patients. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4;14) (95% CI: 0.48–0.96; 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). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4;14) and amp1q21.
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U2 - 10.1038/s41408-022-00768-5
DO - 10.1038/s41408-022-00768-5
M3 - Article
C2 - 36631458
AN - SCOPUS:85146127686
SN - 2044-5385
VL - 13
JO - Blood cancer journal
JF - Blood cancer journal
IS - 1
M1 - 14
ER -