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.; MASSZI T.; GRZASKO N.; HANSSON M.; SANDHU I.; POUR Luděk; VITERBO L.; JACKSON S.R.; STOPPA A.M.; GIMSING P.; HAMADANI M.; BORSARU G.; BERG D.; LIN J.C.; DI BACCO A.; VAN DE VELDE H.; RICHARDSON P.G.; MOREAU P.
• Year of publication: 2017
• Type: Article in Periodical
• Magazine / Source: haematologica
• MU Faculty or unit: Faculty of Medicine
• web: http://dx.doi.org/10.3324/haematol.2017.170118
• Doi: https://doi.org/10.3324/haematol.2017.170118
• Field: Oncology and hematology
• Keywords: ixazomib-lenalidomide-dexamethasone; placebo-lenalidomide-dexamethasone
• Description: 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.