B01 | ANALYSIS OF SUSTAINED MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE WITH OR WITHOUT ISATUXIMAB (PHASE III ISKIA TRIAL)

Background. The phase III IsKia trial evaluated isatuximab-carfilzomib-lenalidomide-dexamethasone (IsaKRd) as pre-ASCT induction and post-ASCT consolidation vs KRd in NDMM patients (pts). Here we report the rates of 1-year sustained (sust)MRD negativity and results from the light consolidation phase. Methods. Transplant-eligible NDMM pts aged <70 years were enrolled. IsaKRd pts received 4 full-dose IsaKRd induction cycles, MEL200-ASCT, 4 full-dose IsaKRd consolidation cycles, and, thereafter, 12 28-day light consolidation cycles [Isa 10 mg/kg IV on days (dd) 1, 15; K 56 mg/m<sup>2</sup> IV dd 1; R 10 mg PO daily dd 1–21; d 20 mg PO dd 1, 15]. Pts in the KRd arm received the same KRd schedule used in the other arm. MRD was assessed by NGS in all pts who achieved ≥VGPR. 1-year sustMRD negativity was defined as 2 sequential MRD-negative evaluations at least 1 year apart. Based on the ITT principle, pts with missing MRD data or who did not achieve VGPR were considered as MRD positive. The data cut-off was 22/7/2024. Results. 151 vs 151 pts were randomly assigned to IsaKRd vs KRd. Pt characteristics were well balanced. The median follow-up was 35 months (IQR 32–38). In the ITT analysis, the MRD negativity rates at the 10<sup>-5</sup> cut-off after full-dose consolidation were 77% vs 67% (OR 1.67; p=0.049) with IsaKRd vs KRd; the rates of 10<sup>-5</sup> 1-year sustMRD negativity after light consolidation were 66% vs 59% (OR 1.36; p=0.21). The MRD negativity rates at the 10<sup>-6</sup> cut-off after full-dose consolidation were 67% vs 48% (OR 2.29; p<0.001) with IsaKRd vs KRd; the rates of 10<sup>-6</sup> 1-year sustMRD negativity after light consolidation were 52% vs 38% (OR 1.82; p=0.012). The 10<sup>-6</sup> 1-year sustMRD negativity advantage with IsaKRd vs KRd was retained in all subgroups. In particular, 62% vs 20% of pts with ≥2 high-risk CA (OR 6.3, 95% CI 1.11–35.66) and 47% vs 35% of pts with R2-ISS III/IV (OR 1.62, 95% CI 0.77–3.41). During light consolidation, the main grade 3–4 hematologic AE was neutropenia (IsaKRd 17% vs KRd 18%); the main grade 3–4 non-hematologic AEs included infections (8% vs 5%), gastrointestinal (4% vs 4%), and vascular AEs (3% vs 1%); discontinuation for toxicity occurred in 3% vs 2%; treatment-related deaths were 2 (1 cerebral ischemia, 1 pulmonary embolism) vs 0. Conclusion. IsaKRd induction-consolidation and prolonged light consolidation significantly increased the rates of 10<sup>-6</sup> sustMRD negativity in NDMM pts (including high-risk pts) without additional safety issues.

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Journal
Haematologica
Published
2025-09-26
DOI
https://doi.org/10.3324/haematol.2025.s1.12853
Primary Topic
Multiple Myeloma Research and Treatments
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B01 | ANALYSIS OF SUSTAINED MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE WITH OR WITHOUT ISATUXIMAB (PHASE III ISKIA TRIAL)

Pieter Sonneveld, Wilfried W. H. Roeloffzen, Mariella Grasso, Laura Rosiñol et al.
Haematologica
Multiple Myeloma Research and Treatments
article

B01 | ANALYSIS OF SUSTAINED MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE WITH OR WITHOUT ISATUXIMAB (PHASE III ISKIA TRIAL)

Pieter Sonneveld, Wilfried W. H. Roeloffzen, Mariella Grasso, Laura Rosiñol, Hermann Einsele, Mario Boccadoro, Irene Attucci, F. Fioritoni, Francesca Gay, Joan Bladé, Meletios Athanasios Dimopoulos, Eirini Katodritou, Marjolein van der Klift, Silvia Mangiacavalli, M. D’Agostino, Albert Oriol, Elena Zamagni, Gloria Margiotta Casaluci, Annemiek Broijl, Angelo Belotti, Fredrik Schjesvold, Paula Rodríguez‐Otero, Giovanni Maria De Sabbata, Mark van Duin, P. Musto, Roman Hájek, Massimo Offidani, P. Tosi, Ka Lung Wu
article en

Abstract

Background. The phase III IsKia trial evaluated isatuximab-carfilzomib-lenalidomide-dexamethasone (IsaKRd) as pre-ASCT induction and post-ASCT consolidation vs KRd in NDMM patients (pts). Here we report the rates of 1-year sustained (sust)MRD negativity and results from the light consolidation phase. Methods. Transplant-eligible NDMM pts aged <70 years were enrolled. IsaKRd pts received 4 full-dose IsaKRd induction cycles, MEL200-ASCT, 4 full-dose IsaKRd consolidation cycles, and, thereafter, 12 28-day light consolidation cycles [Isa 10 mg/kg IV on days (dd) 1, 15; K 56 mg/m<sup>2</sup> IV dd 1; R 10 mg PO daily dd 1–21; d 20 mg PO dd 1, 15]. Pts in the KRd arm received the same KRd schedule used in the other arm. MRD was assessed by NGS in all pts who achieved ≥VGPR. 1-year sustMRD negativity was defined as 2 sequential MRD-negative evaluations at least 1 year apart. Based on the ITT principle, pts with missing MRD data or who did not achieve VGPR were considered as MRD positive. The data cut-off was 22/7/2024. Results. 151 vs 151 pts were randomly assigned to IsaKRd vs KRd. Pt characteristics were well balanced. The median follow-up was 35 months (IQR 32–38). In the ITT analysis, the MRD negativity rates at the 10<sup>-5</sup> cut-off after full-dose consolidation were 77% vs 67% (OR 1.67; p=0.049) with IsaKRd vs KRd; the rates of 10<sup>-5</sup> 1-year sustMRD negativity after light consolidation were 66% vs 59% (OR 1.36; p=0.21). The MRD negativity rates at the 10<sup>-6</sup> cut-off after full-dose consolidation were 67% vs 48% (OR 2.29; p<0.001) with IsaKRd vs KRd; the rates of 10<sup>-6</sup> 1-year sustMRD negativity after light consolidation were 52% vs 38% (OR 1.82; p=0.012). The 10<sup>-6</sup> 1-year sustMRD negativity advantage with IsaKRd vs KRd was retained in all subgroups. In particular, 62% vs 20% of pts with ≥2 high-risk CA (OR 6.3, 95% CI 1.11–35.66) and 47% vs 35% of pts with R2-ISS III/IV (OR 1.62, 95% CI 0.77–3.41). During light consolidation, the main grade 3–4 hematologic AE was neutropenia (IsaKRd 17% vs KRd 18%); the main grade 3–4 non-hematologic AEs included infections (8% vs 5%), gastrointestinal (4% vs 4%), and vascular AEs (3% vs 1%); discontinuation for toxicity occurred in 3% vs 2%; treatment-related deaths were 2 (1 cerebral ischemia, 1 pulmonary embolism) vs 0. Conclusion. IsaKRd induction-consolidation and prolonged light consolidation significantly increased the rates of 10<sup>-6</sup> sustMRD negativity in NDMM pts (including high-risk pts) without additional safety issues.

HaematologicaVol. 110(s1)
Marche Polytechnic University (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Oslo University Hospital (NO), University Medical Center Groningen (NL), University of Oslo (NO), University of Ostrava (CZ), National and Kapodistrian University of Athens (GR), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Theageneio General Hospital (GR), Institute for Stem Cell Biology and Regenerative Medicine (IN), University Hospital Ostrava (CZ), European Heart Network (BE), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Amphia Ziekenhuis (NL), Institut Català d'Oncologia (ES), Amyloidosis Foundation (US), Azienda Ospedaliero-Universitaria Careggi (IT), Istituto di Ematologia di Bologna (IT), Azienda Ospedaliero Universitaria Maggiore della Carita (IT), Universitätsklinikum Würzburg (DE), Ospedale Infermi di Rimini (IT), Clinica Universidad de Navarra (ES), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Azienda USL di Pescara (IT), Erasmus MC Cancer Institute (NL), Policlinico San Matteo Fondazione (IT), Ospedale degli Infermi (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Sanitaria Universitaria Integrata di Trieste (IT)
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