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

MATEOS, M.V., T. MASSZI, N. GRZASKO, M. HANSSON, I. SANDHU, Luděk POUR, L. VITERBO, S.R. JACKSON, A.M. STOPPA, P. GIMSING, M. HAMADANI, G. BORSARU, D. BERG, J.C. LIN, A. DI BACCO, H. VAN DE VELDE, P.G. RICHARDSON and P. MOREAU. 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. haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2017, vol. 102, No 10, p. 1767-1775. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2017.170118.

Basic information

• Original name: 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
• Authors: MATEOS, M.V., T. MASSZI, N. GRZASKO, M. HANSSON, I. SANDHU, Luděk POUR, L. VITERBO, S.R. JACKSON, A.M. STOPPA, P. GIMSING, M. HAMADANI, G. BORSARU, D. BERG, J.C. LIN, A. DI BACCO, H. VAN DE VELDE, P.G. RICHARDSON and P. MOREAU.
• Edition: haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2017, 0390-6078.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30200 3.2 Clinical medicine
• Country of publisher: Italy
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 9.090
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.3324/haematol.2017.170118
• UT WoS: 000411964200029
• Keywords in English: ixazomib-lenalidomide-dexamethasone; placebo-lenalidomide-dexamethasone
• Tags: EL OK
• Tags: International impact, Reviewed

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 similar to 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 -naive patients, HR 0.744 and 0.700 in immunomodulatory-drug-exposed and -naive 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.