Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma
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Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. / Leypoldt, Lisa B; Tichy, Diana; Besemer, Britta; Hänel, Mathias; Raab, Marc S; Mann, Christoph; Munder, Markus; Reinhardt, Hans Christian; Nogai, Axel; Görner, Martin; Ko, Yon-Dschun; de Wit, Maike; Salwender, Hans; Scheid, Christof; Graeven, Ullrich; Peceny, Rudolf; Staib, Peter; Dieing, Annette; Einsele, Hermann; Jauch, Anna; Hundemer, Michael; Zago, Manola; Požek, Ema; Benner, Axel; Bokemeyer, Carsten; Goldschmidt, Hartmut; Weisel, Katja C.
in: J CLIN ONCOL, Jahrgang 42, Nr. 1, 01.01.2024, S. 26-37.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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
PY - 2024/1/1
Y1 - 2024/1/1
N2 - 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.
AB - 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.
U2 - 10.1200/JCO.23.01696
DO - 10.1200/JCO.23.01696
M3 - SCORING: Journal article
C2 - 37753960
VL - 42
SP - 26
EP - 37
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 1
ER -
