Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma

被引：80

作者：

Leypoldt, Lisa B. ^{[1
]}

Tichy, Diana ^{[2
]}

Besemer, Britta ^{[3
]}

Haenel, Mathias ^{[4
]}

Raab, Marc S. ^{[5
,6
]}

Mann, Christoph ^{[7
]}

Munder, Markus ^{[8
]}

Reinhardt, Hans Christian ^{[9
]}

Nogai, Axel ^{[10
]}

Goerner, Martin ^{[11
]}

Ko, Yon-Dschun ^{[12
]}

de Wit, Maike ^{[13
]}

Salwender, Hans ^{[14
]}

Scheid, Christof ^{[15
]}

Graeven, Ullrich ^{[16
]}

Peceny, Rudolf ^{[17
]}

Staib, Peter ^{[18
]}

Dieing, Annette ^{[19
]}

Einsele, Hermann ^{[20
]}

Jauch, Anna ^{[21
]}

Hundemer, Michael ^{[22
]}

Zago, Manola ^{[23
]}

Pozek, Ema ^{[2
]}

Benner, Axel ^{[2
]}

Bokemeyer, Carsten ^{[1
]}

Goldschmidt, Hartmut ^{[24
]}

Weisel, Katja C. ^{[1
,25
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Hematol Oncol & Bone Marrow Transplantat, Sect Pneumol, Hamburg, Germany

[2] German Canc Res Ctr DKFZ Heidelberg, Div Biostat, Heidelberg, Germany

[3] Univ Hosp Tuebingen, Dept Hematol Oncol Immunol & Rheumatol, Tubingen, Germany

[4] Klinikum Chemnitz, Dept Hematol Oncol & Bone Marrow Transplantat, Chemnitz, Germany

[5] Univ Hosp Heidelberg, Internal Med 5, Heidelberg, Germany

[6] Univ Hosp Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany

[7] Univ Hosp Giessen & Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany

[8] Univ Med Ctr Mainz, Dept Internal Med 3, Mainz, Germany

[9] Univ Duisburg Essen, Dept Hematol & Stem Cell Transplantat, Univ Hosp Essen, German Canc Consortium DKTK Partner Site Essen, Essen, Germany

[10] Charite Univ Med Berlin, Dept Internal Med, Berlin, Germany

[11] Klinikum Bielefeld Mitte, Dept Hematol Oncol & Palliat Care, Bielefeld, Germany

[12] Johanniter Krankenhaus Bonn, Dept Internal Med Hematol & Oncol, Bonn, Germany

[13] Vivantes Klinikum Neuk, Dept Internal Med Hematol Oncol & Palliat Med, Berlin, Germany

[14] Asklepios Tumorzentrum Hamburg, AK Altona & AK St Georg, Hamburg, Germany

[15] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany

[16] Kliniken Maria Hilf, Dept Hematol Oncol & Gastroenterol, Monchengladbach, Germany

[17] Klinikum Osnabruck, Dept Oncol Hematol & Stem Cell Transplantat, Osnabruck, Germany

[18] St Antonius Hosp Eschweiler, Dept Hematol & Oncol, Germany18, Eschweiler, Germany

[19] Vivantes Klinikum Urban, Dept Hematol & Oncol, Berlin, Germany

[20] Univ Hosp Wurzburg, Dept Internal Med 2, Wurzburg, Germany

[21] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany

[22] Univ Hosp Heidelberg, Internal Med 5, Heidelberg, Germany

[23] Univ Hosp Tuebingen, Ctr Clin Trials, Tubingen, Germany

[24] Univ Hosp Heidelberg, Internal Med 5, GMMG Studygrp, Heidelberg, Germany

[25] Univ Med Ctr Hamburg Eppendorf, Bldg 043,1,R 104,Martinistr 52, D-20246 Hamburg, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2024年 / 42卷 / 01期

关键词：

BORTEZOMIB; TRANSPLANTATION; DARATUMUMAB; INDUCTION; CONSENSUS;

D O I：

10.1200/JCO.23.01696

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：26 / +

页数：21

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