Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma

Media type: E-Article

Title: Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma

Contributor: Leypoldt, Lisa [Author]; Tichy, Diana [Author]; Besemer, Britta [Author]; Hänel, Mathias [Author]; Raab, Marc-Steffen [Author]; Mann, Christoph [Author]; Munder, Markus [Author]; Reinhardt, Hans Christian [Author]; Nogai, Axel [Author]; Görner, Martin [Author]; Ko, Yon-Dschun [Author]; de Wit, Maike [Author]; Salwender, Hans [Author]; Scheid, Christof [Author]; Graeven, Ullrich [Author]; Peceny, Rudolf [Author]; Staib, Peter [Author]; Dieing, Annette [Author]; Einsele, Hermann [Author]; Jauch, Anna [Author]; Hundemer, Michael [Author]; Zago, Manola [Author]; Požek, Ema [Author]; Benner, Axel [Author]; Bokemeyer, Carsten [Author]; Goldschmidt, Hartmut [Author]; Weisel, Katja C. [Author]

Published: January 2024

Language: English

DOI: 10.1200/JCO.23.01696

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Origination:

Footnote: Veröffentlicht: 27. September 2023

Description: Purpose - The GMMG-CONCEPT trial investigated isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in transplant-eligible (TE) and transplant-noneligible (TNE) patients with newly diagnosed multiple myeloma (NDMM) with exclusively high-risk disease for whom prospective trials are limited, aiming to induce minimal residual disease (MRD) negativity. - Methods - This academic, investigator-initiated, multicenter, phase II trial enrolled patients with high-risk NDMM (HRNDMM) defined by mandatory International Staging System stage II/III combined with del17p, t(4;14), t(14;16), or more than three 1q21 copies as high-risk cytogenetic aberrations (HRCAs). Patients received Isa-KRd induction/consolidation and Isa-KR maintenance. TE patients received high-dose melphalan. TNE patients received two additional Isa-KRd cycles postinduction. This prespecified interim analysis (IA) reports the primary end point, MRD negativity (<10−5, next-generation flow), at the end of consolidation. The secondary end point was progression-free survival (PFS). - Results - Among 125 patients with HRNDMM (TE-intention-to-treat [ITT]-IA, 99; TNE-ITT, 26) of the IA population for the primary end point, the median age was 58 (TE-ITT-IA) and 74 (TNE-ITT) years. Del17p was the most common HRCA (TE, 44.4%; TNE, 42.3%); about one third of evaluable TE/TNE patients presented two or more HRCAs, respectively. The trial met its primary end point with MRD negativity rates after consolidation of 67.7% (TE) and 54.2% (TNE) of patients. Eighty-one of 99 TE-ITT-IA patients reached MRD negativity at any time point (81.8%). MRD negativity was sustained for ≥1 year in 62.6% of patients. With a median follow-up of 44 (TE) and 33 (TNE) months, median PFS was not reached in either arm. - Conclusion - Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.

Access State: Open Access

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