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DARATUMUMAB CARFILZOMIB LENALIDOMIDE AND DEXAMETHASONE AS INDUCTION THERAPY IN HIGH-RISK TRANSPLANT ELIGIBLE NEWLY DIAGNOSED MYELOMA PATIENTS: RESULTS OF THE PHASE 2 STUDY IFM 2018-04
Author(s): ,
Cyrille Touzeau
Affiliations:
CHU Nantes - Hotel Dieu,CHU Nantes - Hotel Dieu,Nantes,France;CHU Nantes - Hotel Dieu,CHU Nantes - Hotel Dieu,Nantes,Frankreich;CHU Nantes - Hotel Dieu,CHU Nantes - Hotel Dieu,Nantes,Francia;CHU Nantes - Hotel Dieu,CHU Nantes - Hotel Dieu,Nantes,France;CHU Nantes - Hotel Dieu,CHU Nantes - Hotel Dieu,Nantes,Francia;CHU Nantes - Hotel Dieu,CHU Nantes - Hotel Dieu,Nantes,Frankrijk;CHU Nantes - Hotel
,
Aurore Perrrot
Affiliations:
Hematology,IUCT Oncopole,Toulouse,France;Hematology,IUCT Oncopole,Toulouse,Frankreich;Hematology,IUCT Oncopole,Toulouse,Francia;Hematology,IUCT Oncopole,Toulouse,France;Hematology,IUCT Oncopole,Toulouse,Francia;Hematology,IUCT Oncopole,Toulouse,Frankrijk;Hematology,IUCT Oncopole,Toulouse,França;Hematology,IUCT Oncopole,Toulouse,Франция ;Hematology,IUCT Oncopole,Toulouse,Frankrike
,
Cyrille Hulin
Affiliations:
Hematology,CHU Bordeaux,Bordeaux,France;Hematology,CHU Bordeaux,Bordeaux,Frankreich;Hematology,CHU Bordeaux,Bordeaux,Francia;Hematology,CHU Bordeaux,Bordeaux,France;Hematology,CHU Bordeaux,Bordeaux,Francia;Hematology,CHU Bordeaux,Bordeaux,Frankrijk;Hematology,CHU Bordeaux,Bordeaux,França;Hematology,CHU Bordeaux,Bordeaux,Франция ;Hematology,CHU Bordeaux,Bordeaux,Frankrike
,
Salomon Manier
Affiliations:
Hematology,CHU Lille,Lille,France;Hematology,CHU Lille,Lille,Frankreich;Hematology,CHU Lille,Lille,Francia;Hematology,CHU Lille,Lille,France;Hematology,CHU Lille,Lille,Francia;Hematology,CHU Lille,Lille,Frankrijk;Hematology,CHU Lille,Lille,França;Hematology,CHU Lille,Lille,Франция ;Hematology,CHU Lille,Lille,Frankrike
,
Margaret Macro
Affiliations:
Hematology,CHU Caen,Caen,France;Hematology,CHU Caen,Caen,Frankreich;Hematology,CHU Caen,Caen,Francia;Hematology,CHU Caen,Caen,France;Hematology,CHU Caen,Caen,Francia;Hematology,CHU Caen,Caen,Frankrijk;Hematology,CHU Caen,Caen,França;Hematology,CHU Caen,Caen,Франция ;Hematology,CHU Caen,Caen,Frankrike
,
Marie-Lorraine Chretien
Affiliations:
Hematology,CHU Dijon,DIjon,France;Hematology,CHU Dijon,DIjon,Frankreich;Hematology,CHU Dijon,DIjon,Francia;Hematology,CHU Dijon,DIjon,France;Hematology,CHU Dijon,DIjon,Francia;Hematology,CHU Dijon,DIjon,Frankrijk;Hematology,CHU Dijon,DIjon,França;Hematology,CHU Dijon,DIjon,Франция ;Hematology,CHU Dijon,DIjon,Frankrike
,
Lionel Karlin
Affiliations:
Hematology,CHU Lyon,Lyon,France;Hematology,CHU Lyon,Lyon,Frankreich;Hematology,CHU Lyon,Lyon,Francia;Hematology,CHU Lyon,Lyon,France;Hematology,CHU Lyon,Lyon,Francia;Hematology,CHU Lyon,Lyon,Frankrijk;Hematology,CHU Lyon,Lyon,França;Hematology,CHU Lyon,Lyon,Франция ;Hematology,CHU Lyon,Lyon,Frankrike
,
Olivier Decaux
Affiliations:
Hematology,CHu Rennes,Rennes,France;Hematology,CHu Rennes,Rennes,Frankreich;Hematology,CHu Rennes,Rennes,Francia;Hematology,CHu Rennes,Rennes,France;Hematology,CHu Rennes,Rennes,Francia;Hematology,CHu Rennes,Rennes,Frankrijk;Hematology,CHu Rennes,Rennes,França;Hematology,CHu Rennes,Rennes,Франция ;Hematology,CHu Rennes,Rennes,Frankrike
,
Caroline Jacquet
Affiliations:
Hematology,CHU Nancy,Nancy,France;Hematology,CHU Nancy,Nancy,Frankreich;Hematology,CHU Nancy,Nancy,Francia;Hematology,CHU Nancy,Nancy,France;Hematology,CHU Nancy,Nancy,Francia;Hematology,CHU Nancy,Nancy,Frankrijk;Hematology,CHU Nancy,Nancy,França;Hematology,CHU Nancy,Nancy,Франция ;Hematology,CHU Nancy,Nancy,Frankrike
,
Mourad Tiab
Affiliations:
Hematology,CHD,La Roche sur Yon,France;Hematology,CHD,La Roche sur Yon,Frankreich;Hematology,CHD,La Roche sur Yon,Francia;Hematology,CHD,La Roche sur Yon,France;Hematology,CHD,La Roche sur Yon,Francia;Hematology,CHD,La Roche sur Yon,Frankrijk;Hematology,CHD,La Roche sur Yon,França;Hematology,CHD,La Roche sur Yon,Франция ;Hematology,CHD,La Roche sur Yon,Frankrike
,
Xavier Leleu
Affiliations:
Hematology,CHU Poitiers,Poitiers,France;Hematology,CHU Poitiers,Poitiers,Frankreich;Hematology,CHU Poitiers,Poitiers,Francia;Hematology,CHU Poitiers,Poitiers,France;Hematology,CHU Poitiers,Poitiers,Francia;Hematology,CHU Poitiers,Poitiers,Frankrijk;Hematology,CHU Poitiers,Poitiers,França;Hematology,CHU Poitiers,Poitiers,Франция ;Hematology,CHU Poitiers,Poitiers,Frankrike
,
Lucie Planchce
Affiliations:
Biostatistic,CHU Nantes,Nantes,France;Biostatistic,CHU Nantes,Nantes,Frankreich;Biostatistic,CHU Nantes,Nantes,Francia;Biostatistic,CHU Nantes,Nantes,France;Biostatistic,CHU Nantes,Nantes,Francia;Biostatistic,CHU Nantes,Nantes,Frankrijk;Biostatistic,CHU Nantes,Nantes,França;Biostatistic,CHU Nantes,Nantes,Франция ;Biostatistic,CHU Nantes,Nantes,Frankrike
,
Hervé Avet-Loiseau
Affiliations:
Hematology,IUCT Oncopole,Toulouse,France;Hematology,IUCT Oncopole,Toulouse,Frankreich;Hematology,IUCT Oncopole,Toulouse,Francia;Hematology,IUCT Oncopole,Toulouse,France;Hematology,IUCT Oncopole,Toulouse,Francia;Hematology,IUCT Oncopole,Toulouse,Frankrijk;Hematology,IUCT Oncopole,Toulouse,França;Hematology,IUCT Oncopole,Toulouse,Франция ;Hematology,IUCT Oncopole,Toulouse,Frankrike
Philippe Moreau
Affiliations:
Hematology,CHU Nantes,Nantes,France;Hematology,CHU Nantes,Nantes,Frankreich;Hematology,CHU Nantes,Nantes,Francia;Hematology,CHU Nantes,Nantes,France;Hematology,CHU Nantes,Nantes,Francia;Hematology,CHU Nantes,Nantes,Frankrijk;Hematology,CHU Nantes,Nantes,França;Hematology,CHU Nantes,Nantes,Франция ;Hematology,CHU Nantes,Nantes,Frankrike
(Abstract release date: 05/12/22) EHA Library. Touzeau C. 06/10/22; 357040; S176
Cyrille Touzeau
Cyrille Touzeau
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S176

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background
High-risk (HR) cytogenetic is associated with poor outcome in transplant eligible (TE) newly diagnosed myeloma multiple myeloma (NDMM). The triplet combination carfilzomib lenalidomide and dexamethasone (KRD) plus transplantation demonstrated high efficacy with favorable safety profile in TE-NDMM patients (FORTE). The addition of daratumumab (Dara) to frontline therapy also improved response rate and progression free-survival in TE-NDMM patients (CASSIOPEIA, GRIFFIN). Double transplant also improved outcome of HR TE NDMM patients (EMN02, STAMINA).

Aims

The phase 2 trial 2018-04 from the Intergroupe Francophone du Myelome (IFM) is evaluating an intensive strategy with Dara-KRD induction and consolidation plus double transplant in HR TE NDMM (NCT03606577).

Methods
HR MM was defined by the presence of del17p, t(4;14) and/or t(14;16). Stategy includes Dara-KRD induction (6 cycles), autologous stem cell transplantation (ASCT), Dara-KRD consolidation (4 cycles), second ASCT, Dara-lenalidomide maintenance. The primary endpoint was the feasibility of this intensive strategy. Here, we report efficacy and safety analysis of Dara-KRD induction.

Results
Fifty patients with previously untreated NDMM were included from july 2019 to march 2021 in 11 IFM centers Median age was 57 (range 38 -65). ISS stage 3 was present in 12 (24%) patients. Based on inclusion criteria, all patients had HR cytogenetic, including 17p deletion (n=20, 40%), t(4;14) (n=26, 52%) or t(14;16) (n=10,20%). Forty-six patients completed Dara-KRD induction. Two patients discontinued treatment due to severe adverse event (COVID-19 infection, n=1 ; drug-induced hepatitis, n=1) and 2 patients discontinued treatment due to disease progression. Grade 3-4 treatment related adverse event (>5% of patients) were neutropenia (38%), anemia (14%), thrombocytopenia (8%), infection (6%), renal insufficiency (6%) and deep-vein thrombosis (6%). Two patients (6%) experienced stem-cell collection failure. Overall response rate was 96%, including 92 % > very good partial response. Among 37/46 evaluable patients post induction, Minimal Residual Disease negativity rate (NGS, 10-5) was 62%. 

Conclusion
Dara-KRD as induction prior ASCT is safe and allows deep responses in TE NDMM patients with high-risk cytogenetic profile. IFM 2018-04 study is ongoing and longer follow-up is needed to evaluate safety and efficacy of the overall strategy with Dara-KRD induction and consolidation plus double transplant in this subset of HR patients.

Keyword(s): Autologous stem cell collection, High risk, Myeloma

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S176

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background
High-risk (HR) cytogenetic is associated with poor outcome in transplant eligible (TE) newly diagnosed myeloma multiple myeloma (NDMM). The triplet combination carfilzomib lenalidomide and dexamethasone (KRD) plus transplantation demonstrated high efficacy with favorable safety profile in TE-NDMM patients (FORTE). The addition of daratumumab (Dara) to frontline therapy also improved response rate and progression free-survival in TE-NDMM patients (CASSIOPEIA, GRIFFIN). Double transplant also improved outcome of HR TE NDMM patients (EMN02, STAMINA).

Aims

The phase 2 trial 2018-04 from the Intergroupe Francophone du Myelome (IFM) is evaluating an intensive strategy with Dara-KRD induction and consolidation plus double transplant in HR TE NDMM (NCT03606577).

Methods
HR MM was defined by the presence of del17p, t(4;14) and/or t(14;16). Stategy includes Dara-KRD induction (6 cycles), autologous stem cell transplantation (ASCT), Dara-KRD consolidation (4 cycles), second ASCT, Dara-lenalidomide maintenance. The primary endpoint was the feasibility of this intensive strategy. Here, we report efficacy and safety analysis of Dara-KRD induction.

Results
Fifty patients with previously untreated NDMM were included from july 2019 to march 2021 in 11 IFM centers Median age was 57 (range 38 -65). ISS stage 3 was present in 12 (24%) patients. Based on inclusion criteria, all patients had HR cytogenetic, including 17p deletion (n=20, 40%), t(4;14) (n=26, 52%) or t(14;16) (n=10,20%). Forty-six patients completed Dara-KRD induction. Two patients discontinued treatment due to severe adverse event (COVID-19 infection, n=1 ; drug-induced hepatitis, n=1) and 2 patients discontinued treatment due to disease progression. Grade 3-4 treatment related adverse event (>5% of patients) were neutropenia (38%), anemia (14%), thrombocytopenia (8%), infection (6%), renal insufficiency (6%) and deep-vein thrombosis (6%). Two patients (6%) experienced stem-cell collection failure. Overall response rate was 96%, including 92 % > very good partial response. Among 37/46 evaluable patients post induction, Minimal Residual Disease negativity rate (NGS, 10-5) was 62%. 

Conclusion
Dara-KRD as induction prior ASCT is safe and allows deep responses in TE NDMM patients with high-risk cytogenetic profile. IFM 2018-04 study is ongoing and longer follow-up is needed to evaluate safety and efficacy of the overall strategy with Dara-KRD induction and consolidation plus double transplant in this subset of HR patients.

Keyword(s): Autologous stem cell collection, High risk, Myeloma

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