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

. 2017 Oct ; 102 (10) : 1767-1775. [epub] 20170727

Jazyk angličtina Země Itálie Médium print-electronic

Typ dokumentu klinické zkoušky, fáze III, časopisecké články, randomizované kontrolované studie

Perzistentní odkaz   https://www.medvik.cz/link/pmid28751562
Odkazy

PubMed 28751562
PubMed Central PMC5622861
DOI 10.3324/haematol.2017.170118
PII: haematol.2017.170118
Knihovny.cz E-zdroje

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.

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Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood. 2008;111(5):2521–2526. PubMed

Kastritis E, Zervas K, Symeonidis A, et al. Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia. 2009;23(6):1152–1157. PubMed

Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007;25(15):1993–1999. PubMed

Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122–1128. PubMed PMC

Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516–2520. PubMed PMC

Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867–874. PubMed

Brioli A, Melchor L, Cavo M, Morgan GJ. The impact of intra-clonal heterogeneity on the treatment of multiple myeloma. Br J Haematol. 2014;165(4):441–454. PubMed

Jagannath S, Roy A, Kish J, et al. Real-world treatment patterns and associated progression-free survival in relapsed/refractory multiple myeloma among US community oncology practices. Expert Rev Hematol. 2016;9(7):707–717. PubMed

Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26(1):149–157. PubMed PMC

San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055–1066. PubMed

Willenbacher E, Weger R, Rochau U, Siebert U, Willenbacher W. Real-world use of 3rd line therapy for multiple myeloma in Austria: an Austrian Myeloma Registry (AMR) analysis of the therapeutic landscape and clinical outcomes prior to the use of next generation myeloma therapeutics. PLoS One. 2016;11(3):e0147381. PubMed PMC

Vogl DT, Stadtmauer EA, Richardson PG, et al. Impact of prior therapies on the relative efficacy of bortezomib compared with dexamethasone in patients with relapsed/refractory multiple myeloma. Br J Haematol. 2009;147(4):531–534. PubMed

Wang M, Dimopoulos MA, Chen C, et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood. 2008;112(12):4445–4451. PubMed

Conner TM, Doan QD, Walters IB, LeBlanc AL, Beveridge RA. An observational, retrospective analysis of retreatment with bortezomib for multiple myeloma. Clin Lymphoma Myeloma. 2008;8(3):140–145. PubMed

Oriol A, Giraldo P, Kotsianidis I, et al. Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study. Hematology. 2015;20(7):405–409. PubMed

Petrucci MT, Giraldo P, Corradini P, et al. A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma. Br J Haematol. 2013;160(5):649–659. PubMed

Wolf J, Richardson PG, Schuster M, LeBlanc A, Walters IB, Battleman DS. Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series. Clin Adv Hematol Oncol. 2008;6(10):755–760. PubMed

Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621–1634. PubMed

Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011; 117(18):4691–4695. PubMed PMC

Sonneveld P, Broijl A. Treatment of relapsed and refractory multiple myeloma. Haematologica. 2016;101(4):396–406. PubMed PMC

Moreau P, Joshua D, Chng WJ, et al. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study. Leukemia. 2016;31(1):115–122. PubMed PMC

Avet-Loiseau H, Soulier J, Fermand JP, et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia. 2010;24(3):623–628. PubMed

Dimopoulos MA, Stewart AK, Rajkumar SV, et al. Effect of carfilzomib, lenalidomide, and dexamethasone (KRd) vs lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma (RMM) by line of therapy: Secondary analysis from an interim analysis of the phase III study ASPIRE (NCT01080391). J Clin Oncol. 2015;33(15_suppl):abstract 8525.

Bacco Di A, Bahlis NJ, Munshi NC, et al. Higher c-MYC expression is associated with ixazomib-lenalidomide-dexamethasone (IRd) progression-free survival (PFS) benefit versus placebo-Rd: biomarker analysis of the phase 3 tourmaline-MM1 study in relapsed/refractory multiple myeloma (RRMM). Blood. 2016;128(22):abstract 243

Chen S, Blank JL, Peters T, et al. Genome-wide siRNA screen for modulators of cell death induced by proteasome inhibitor bortezomib. Cancer Res. 2010;70(11):4318–4326. PubMed

Chng WJ, Gertz MA, Chung TH, et al. Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31–32 deletion as a prognostic factor in myeloma. Leukemia. 2010;24(4):833–842. PubMed PMC

Ravi D, Beheshti A, Abermil N, et al. Proteasomal inhibition by ixazomib induces CHK1 and MYC-dependent cell death in T-cell and hodgkin lymphoma. Cancer Res. 2016;76(11):3319–333. PubMed PMC

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ClinicalTrials.gov
NCT01564537

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