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Haematologica. 2017 Oct;102(10):1767-1775. doi: 10.3324/haematol.2017.170118. Epub 2017 Jul 27.

Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1.

Author information

1
Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Spain.
2
St. István, St. László Hospital, 3 Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
3
Medical University of Lublin and St John's Cancer Center, Lublin, Poland.
4
Skåne University Hospital, Lund University, Sweden.
5
University of Alberta Edmonton, Canada.
6
University Hospital Brno, Czech Republic.
7
Instituto Português de Oncologia do Porto Francisco Gentil, Entidade Pública Empresarial (IPOPFG, EPE), Portugal.
8
Middlemore Hospital, Auckland, New Zealand.
9
Institut Paoli-Calmettes, Marseille, France.
10
University Hospital Rigshospitalet, Copenhagen, Denmark.
11
Medical College of Wisconsin, Milwaukee, WI, USA.
12
Spitalul Clinic Coltea, Bucharest, Romania.
13
Millennium Pharmaceuticals Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
14
Dana-Farber Cancer Institute, Boston, MA, USA.
15
University Hospital Hôtel Dieu, Nantes, France.

Abstract

Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes with subsequent therapies. We analyzed efficacy and safety according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy and safety were evaluated in subgroups defined according to type (proteasome inhibitor [PI] and immunomodulatory drug) and number (1 vs. 2 or 3) of prior therapies received. Of 722 patients, 503 (70%) had received a prior PI, and 397 (55%) prior lenalidomide/thalidomide; 425 patients had received 1 prior therapy, and 297 received 2 or 3 prior therapies. At a median follow up of ~15 months, PFS was prolonged with ixazomib-Rd vs. placebo-Rd regardless of type of prior therapy received; HR 0.739 and 0.749 in PI-exposed and -naïve patients, HR 0.744 and 0.700 in immunomodulatory-drug-exposed and -naïve patients, respectively. PFS benefit with ixazomib-Rd vs. placebo-Rd appeared greater in patients with 2 or 3 prior therapies (HR 0.58) and in those with 1 prior therapy without prior transplant (HR 0.60) versus those with 1 prior therapy and transplant (HR 1.23). Across all subgroups, toxicity was consistent with that seen in the intent-to-treat population. In patients with relapsed/refractory multiple myeloma, ixazomib-Rd was associated with a consistent clinical benefit vs. placebo-Rd regardless of prior treatment with bortezomib or immunomodulatory drugs. Patients with 2 or 3 prior therapies, or 1 prior therapy without transplant seemed to have greater benefit than patients with 1 prior therapy and transplant. TOURMALINE-MM1 registered at clinicaltrials.gov identifier: 01564537.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01564537.

PMID:
28751562
PMCID:
PMC5622861
DOI:
10.3324/haematol.2017.170118
[Indexed for MEDLINE]
Free PMC Article

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