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

María Victoria Mateos, T. Masszi, Norbert Grzasko, Markus Hansson, Irwindeep Sandhu, Ludek Pour, Luísa Viterbo, Sharon R. Jackson, Anne Marie Stoppa, Peter Gimsing, Mehdi Hamadani, Gabriela Borsaru, Deborah Berg, Jianchang Lin, Alessandra Di Bacco, Helgi Van De Velde, Paul G. Richardson, Philippe Moreau

Research output: Article

17 Citations (Scopus)

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-dexam-ethasone (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 (pro-teasome 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.

Original languageEnglish
Pages (from-to)1767-1775
Number of pages9
JournalHaematologica
Volume102
Issue number10
DOIs
Publication statusPublished - szept. 30 2017

Fingerprint

Multiple Myeloma
Dexamethasone
Placebos
Safety
Therapeutics
Transplants
lenalidomide
Pharmaceutical Preparations
Thalidomide
ixazomib

ASJC Scopus subject areas

  • Hematology

Cite this

Impact of prior therapy on the efficacy and safety of oral ixazomiblenalidomide-dexamethasone vs. Placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1. / Mateos, María Victoria; Masszi, T.; Grzasko, Norbert; Hansson, Markus; Sandhu, Irwindeep; Pour, Ludek; Viterbo, Luísa; Jackson, Sharon R.; Stoppa, Anne Marie; Gimsing, Peter; Hamadani, Mehdi; Borsaru, Gabriela; Berg, Deborah; Lin, Jianchang; Di Bacco, Alessandra; Van De Velde, Helgi; Richardson, Paul G.; Moreau, Philippe.

In: Haematologica, Vol. 102, No. 10, 30.09.2017, p. 1767-1775.

Research output: Article

Mateos, MV, Masszi, T, Grzasko, N, Hansson, M, Sandhu, I, Pour, L, Viterbo, L, Jackson, SR, Stoppa, AM, Gimsing, P, Hamadani, M, Borsaru, G, Berg, D, Lin, J, Di Bacco, A, Van De Velde, H, Richardson, PG & Moreau, P 2017, 'Impact of prior therapy on the efficacy and safety of oral ixazomiblenalidomide-dexamethasone vs. Placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1', Haematologica, vol. 102, no. 10, pp. 1767-1775. https://doi.org/10.3324/haematol.2017.170118
Mateos, María Victoria ; Masszi, T. ; Grzasko, Norbert ; Hansson, Markus ; Sandhu, Irwindeep ; Pour, Ludek ; Viterbo, Luísa ; Jackson, Sharon R. ; Stoppa, Anne Marie ; Gimsing, Peter ; Hamadani, Mehdi ; Borsaru, Gabriela ; Berg, Deborah ; Lin, Jianchang ; Di Bacco, Alessandra ; Van De Velde, Helgi ; Richardson, Paul G. ; Moreau, Philippe. / Impact of prior therapy on the efficacy and safety of oral ixazomiblenalidomide-dexamethasone vs. Placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1. In: Haematologica. 2017 ; Vol. 102, No. 10. pp. 1767-1775.
@article{95f98aaf05494d0092cd649d1c799550,
title = "Impact of prior therapy on the efficacy and safety of oral ixazomiblenalidomide-dexamethasone vs. Placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1",
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-dexam-ethasone (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 (pro-teasome 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 –na{\"i}ve patients, HR 0.744 and 0.700 in immunomodulatory-drug-exposed and -na{\"i}ve 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.",
author = "Mateos, {Mar{\'i}a Victoria} and T. Masszi and Norbert Grzasko and Markus Hansson and Irwindeep Sandhu and Ludek Pour and Lu{\'i}sa Viterbo and Jackson, {Sharon R.} and Stoppa, {Anne Marie} and Peter Gimsing and Mehdi Hamadani and Gabriela Borsaru and Deborah Berg and Jianchang Lin and {Di Bacco}, Alessandra and {Van De Velde}, Helgi and Richardson, {Paul G.} and Philippe Moreau",
year = "2017",
month = "9",
day = "30",
doi = "10.3324/haematol.2017.170118",
language = "English",
volume = "102",
pages = "1767--1775",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "10",

}

TY - JOUR

T1 - Impact of prior therapy on the efficacy and safety of oral ixazomiblenalidomide-dexamethasone vs. Placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1

AU - Mateos, María Victoria

AU - Masszi, T.

AU - Grzasko, Norbert

AU - Hansson, Markus

AU - Sandhu, Irwindeep

AU - Pour, Ludek

AU - Viterbo, Luísa

AU - Jackson, Sharon R.

AU - Stoppa, Anne Marie

AU - Gimsing, Peter

AU - Hamadani, Mehdi

AU - Borsaru, Gabriela

AU - Berg, Deborah

AU - Lin, Jianchang

AU - Di Bacco, Alessandra

AU - Van De Velde, Helgi

AU - Richardson, Paul G.

AU - Moreau, Philippe

PY - 2017/9/30

Y1 - 2017/9/30

N2 - 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-dexam-ethasone (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 (pro-teasome 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.

AB - 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-dexam-ethasone (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 (pro-teasome 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.

UR - http://www.scopus.com/inward/record.url?scp=85030316883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030316883&partnerID=8YFLogxK

U2 - 10.3324/haematol.2017.170118

DO - 10.3324/haematol.2017.170118

M3 - Article

C2 - 28751562

AN - SCOPUS:85030316883

VL - 102

SP - 1767

EP - 1775

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 10

ER -