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Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients

Hervé Avet-Loiseau, Nizar J. Bahlis, Wee-Joo Chng, Tamas Masszi, Luisa Viterbo, Ludek Pour, Peter Ganly, Antonio Palumbo, Michele Cavo, Christian Langer, Andrzej Pluta, Arnon Nagler, Shaji Kumar, Dina Ben-Yehuda, S. Vincent Rajkumar, Jesus San-Miguel, Deborah Berg, Jianchang Lin, Helgi van de Velde, Dixie-Lee Esseltine, Alessandra di Bacco, Philippe Moreau and Paul G. Richardson

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  • RE: Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients
    • Pierre Lemieux, 1. Pharmacien Centre hospitalier affilié universitaire régional (CHAUR), Département de pharmacie
    We have read with great interest the Avet-Loiseau analysis of high-risk cytogenetic subjects
    included in the TOURMALINE-MM1 study1. The use of different cutoff for the definition of
    positivity of cytogenetic abnormalities is very interesting, but also raises questions when the 
    authors state that: " the addition of ixazomib to Rd overcomes the poor PFS associated with 
    high-risk cytogenetic abnormalities in patients with relapsed and / or refractory MM ". Indeed, 
    the authors report a PFS of 21.4 months in patients with high-risk cytogenetics compared to 
    20.6 months in standard risk subjects. These results were obtained by using cutoff of 5 %, 3 % 
    and 3 % positive cells respectively for the detection of del(17p), t(4;14), t(14;16). Although 
    positivity thresholds are subject to debate, several authors have demonstrated that thresholds 
    of 60 % is associated with a significant impact on event-free survival and overall survival.2 The 
    authors also highlight two studies in which bortezomib improved the prognosis of patients with 
    a 17p deletion while the cutoff was 10%, unlike the other one who could not demonstrate any 
    advantages of bortezomib while the cutoff was 60 %.3-4 In this study, the PFS results for the 17p 
    deletions decrease to 15.7 months when the cutoff is set to 60%, suggesting a PFS well beyond 
    21.4 months for the 36 subjects with less than 60% cells positive for the del (17p). We would...
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    Conflict of Interest:
    None declared.