Adoption of triplet therapy and clinical outcomes in routine practice among newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant in the USA

ABSTRACT

Background: Immunomodulator (IMID) and proteasome inhibitor (PI) triplet frontline therapy (FT) in newly diagnosed multiple myeloma (NDMM) trials improve overall survival (OS); reported outcomes in routine practice are lacking. Authors compared outcomes in NDMM patients in the USA by use of triplet vs doublet FTs.

Methods: In this retrospective study of NDMM patients without FT transplant between 1/1/2008 and 6/30/2017, FT was categorized as: PI+IMID-triplet (≥ 3 drugs including PI+IMID), non-PI+IMID-triplet (≥ 3 drugs, not PI+IMID), doublet (≤ 2 drugs). Univariate and multivariate analyses identified FT triplet predictors and compared time-to-next-treatment (TTNT)/OS.

Results: Among 4,982 NDMM patients, 68% and 32% initiated doublet and triplet FTs (PI+IMID: 36% in 2017). Triplet FT predictors included: age, cytogenetics, ISS stage, certain CRAB symptoms. Median TTNT_{PI+IMID-triplet} = 18.9 months vs 13.7 (non-PI+IMID-triplet) and 16.5 months (doublet) FTs (P< 0.01); adjusted HR_{PI+IMID-triplet} = 0.86; P= 0.009; HR_{non-PI+IMID-triplet} = 1.10; P = 0.083 vs doublet FT. Median OS_{PI+IMID-triplet} = 58.7 months vs 43.6 (non-PI+IMID-triplet) and 45.7 months (doublet) FTs (P< 0.01); adjusted HR_{PI+IMID-triplet} = 0.83; P= 0.016; HR_{non-PI+IMID-triplet} = 1.02; P = 0.727 vs doublet FT.

Conclusion: PI+IMID-triplet FT is not utilized for most non-frontline-transplant NDMM patients in routine care but is associated with prolonged TTNT/OS.

KEYWORDS:

• Newly diagnosed multiple myeloma
• induction therapy
• triplet therapy

Author contributions

All authors contributed to the design of this research, analyzed the findings and contributed to the drafting and approval of this manuscript.

Declaration of interest

D Romanus, T Skacel, and R Labotka are employees of Takeda. P Hari has received consulting honoraria and research support from Takeda and Celgene; A Raju, E Farrelly, and M Blazer are employees of Xcenda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Funding for this study was provided by Takeda Pharmaceutical Company Limited. The sponsor participated in the development of the protocol, discussion of the results, and review of the manuscript for scientific content.