Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma
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 limit...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 2024
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| In: |
Journal of clinical oncology
Year: 2024, Volume: 42, Issue: 1, Pages: 26-37 |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.23.01696 |
| Online Access: | kostenfrei kostenfrei 
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| Author Notes: | Lisa B. Leypoldt, MD, Diana Tichy, MD, Britta Besemer, MD, Mathias Hänel, MD, Marc S. Raab, MD, Christoph Mann, MD, Markus Munder, MD, Hans Christian Reinhardt, MD, Axel Nogai, MD, Martin Görner, MD, Yon-Dschun Ko, MD, Maike de Wit, MD, Hans Salwender, MD, Christof Scheid, MD, Ullrich Graeven, MD, PhD, Rudolf Peceny, MD, Peter Staib, MD, PhD, Annette Dieing, MD, Hermann Einsele, MD, Anna Jauch, PhD, Michael Hundemer, MD, Manola Zago, PhD, Ema Poz̆ek, MSc, Axel Benner, Dipl Stat,Carsten Bokemeyer, MD, Hartmut Goldschmidt, MD, and Katja C. Weisel, MD |
| Summary: | 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. |
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| Item Description: | Veröffentlicht: 27. September 2023 Gesehen am 13.05.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.23.01696 |