TY - JOUR
T1 - Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma
AU - Leypoldt, Lisa B.
AU - Tichy, Diana
AU - Besemer, Britta
AU - Hänel, Mathias
AU - Raab, Marc S.
AU - Mann, Christoph
AU - Munder, Markus
AU - Reinhardt, Hans Christian
AU - Nogai, Axel
AU - Görner, Martin
AU - Ko, Yon Dschun
AU - De Wit, Maike
AU - Salwender, Hans
AU - Scheid, Christof
AU - Graeven, Ullrich
AU - Peceny, Rudolf
AU - Staib, Peter
AU - Dieing, Annette
AU - Einsele, Hermann
AU - Jauch, Anna
AU - Hundemer, Michael
AU - Zago, Manola
AU - Požek, Ema
AU - Benner, Axel
AU - Bokemeyer, Carsten
AU - Goldschmidt, Hartmut
AU - Weisel, Katja C.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - PURPOSEThe 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.METHODSThis 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).RESULTSAmong 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.CONCLUSIONIsa-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.
AB - PURPOSEThe 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.METHODSThis 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).RESULTSAmong 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.CONCLUSIONIsa-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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U2 - 10.1200/JCO.23.01696
DO - 10.1200/JCO.23.01696
M3 - Article
C2 - 37753960
AN - SCOPUS:85180611898
SN - 0732-183X
VL - 42
SP - 26
EP - 37
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -