UPDATES FROM ICARIA-MM, A PHASE 3 STUDY OF ISATUXIMAB (ISA) PLUS POMALIDOMIDE AND LOW-DOSE DEXAMETHASONE (PD) VERSUS PD IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA (RRMM)
Author(s): ,
Aurore Perrot
Affiliations:
CHU de Toulouse, IUCT-O,Toulouse University Hospital,TOULOUSE,France
,
Paul Richardson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Jesus San-Miguel
Affiliations:
Clinical and Translational Medicine,Clínica Universidad de Navarra, Navarra, CIMA, IDISNA, CIBER-ONC,Pamplona,Spain
,
Meral Beksac
Affiliations:
Department of Hematology,Ankara University,Ankara,Turkey
,
Ivan Spicka
Affiliations:
General Faculty Hospital,Charles University,Prague,Czech Republic
,
Xavier Leleu
Affiliations:
Service d'Hématologie et Thérapie Cellulaire,CHU and CIC Inserm 1402,Poitiers Cedex,France
,
Fredrik Schjesvold
Affiliations:
Oslo Myeloma Center, Oslo University Hospital and KG Jebsen Center for B Cell Malignancies,University of Oslo,Oslo,Norway
,
Philippe Moreau
Affiliations:
University of Nantes,Nantes,France
,
Meletios Dimopoulos
Affiliations:
Department of Clinical Therapeutics, School of Medicine,National and Kapodistrian University of Athens School of Medicine,Athens,Greece
,
Jeffrey Shang-Yi Huang
Affiliations:
Department of Hematology,National Taiwan University Hospital,Taiwan,Taiwan, Province of China
,
Jiri Minarik
Affiliations:
Department of Hemato-Oncology, Faculty of Medicine and Dentistry,Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Michele Cavo
Affiliations:
Department of Experimental, Diagnostic and Specialty Medicine, Seràgnoli Institute of Hematology,University of Bologna,Bologna,Italy
,
H Miles Prince
Affiliations:
Immunology and Molecular Oncology, Epworth Healthcare,University of Melbourne,Melbourne,Australia
,
Cheng Zheng
Affiliations:
Sanofi Oncology,Cambridge,United States
,
Franck Dubin
Affiliations:
Sanofi Oncology Development,Vitry-Sur-Seine,France
,
Helgi van de Velde
Affiliations:
Sanofi Oncology,Cambridge,United States
Kenneth Anderson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
EHA Library. PERROT A. 06/09/21; 324594; S186
AURORE PERROT
AURORE PERROT
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S186

Type: Oral Presentation

Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis

Background
Isa is an approved monoclonal antibody that binds to a specific epitope on the CD38 receptor. The Phase 3 ICARIA-MM study (NCT02990338) demonstrated significantly improved progression-free survival (PFS) with Isa-Pd vs Pd (P=0.001) and a manageable safety profile (Attal M, et al. Lancet 2019;394:2096-2107).

Aims
Here we report updated ICARIA results.

Methods
Pts with RRMM (N=307) who have received ≥2 prior therapies, including lenalidomide (Len) and a proteasome inhibitor (PI), were randomized to Isa-Pd (n=154) or Pd (n=153). Isa was administered intravenously at 10 mg/kg weekly for 4 weeks, and every other week thereafter. This preplanned second interim analysis assessed longer term outcomes, including time to next treatment (TTNT), overall survival (OS), time from randomization to disease progression on first subsequent therapy or death (PFS2), and safety.

Results
Pts had a median of 3 prior lines of therapy (IQR 2–4; table). As of Oct 1, 2020 (median follow-up, 35.3 months [mo]), 27 Isa-Pd pts (18%) vs 12 Pd pts (8%) were still on treatment; 60% vs 72% had proceeded to subsequent therapy. Median TTNT was 15.5 mo with Isa-Pd vs 8.9 mo with Pd (hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.42–0.74; P<0.0001); 24% vs 58% of pts with subsequent therapy received daratumumab (dara). Overall response rate (ORR) in subsequent treatment with dara monotherapy was higher after Pd (38%) than Isa-Pd (14%), but was similar (32% vs 31%) with dara combination therapy (table). Median PFS2 in the intent-to-treat population was 17.5 mo with Isa-Pd vs 12.9 mo with Pd (HR 0.76; 95% CI 0.58–0.99; P=0.0202). Median OS was 24.6 mo with Isa-Pd vs 17.7 mo with Pd (HR 0.76; 95% CI 0.58–1.01; one-sided P=0.0280). Median treatment duration was 47.6 weeks (range 1.3–171.6) with Isa-Pd vs 24.0 weeks (range 1.0–168.6) with Pd. Serious treatment-emergent adverse event (TEAEs) were seen in 73% of Isa-Pd pts vs 60% of Pd pts. Most frequent non-hematologic TEAEs (any grade) with Isa-Pd were infusion reaction (38%), upper respiratory tract infection (34%), and diarrhea (30%). Grade 3–4 neutropenia (85% vs 71%) and thrombocytopenia (34% vs 25%) were more frequent with Isa-Pd than with Pd.

Conclusion
Isa-Pd demonstrates a significant improvement in TTNT and PFS2 compared with Pd. A strong trend in OS benefit was also seen in the Isa-Pd arm, with approximately 7 mo improvement in median OS. The overall safety profile remains unchanged from prior analyses.

Keyword(s): CD38, Monoclonal antibody, Multiple myeloma, Phase III

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S186

Type: Oral Presentation

Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis

Background
Isa is an approved monoclonal antibody that binds to a specific epitope on the CD38 receptor. The Phase 3 ICARIA-MM study (NCT02990338) demonstrated significantly improved progression-free survival (PFS) with Isa-Pd vs Pd (P=0.001) and a manageable safety profile (Attal M, et al. Lancet 2019;394:2096-2107).

Aims
Here we report updated ICARIA results.

Methods
Pts with RRMM (N=307) who have received ≥2 prior therapies, including lenalidomide (Len) and a proteasome inhibitor (PI), were randomized to Isa-Pd (n=154) or Pd (n=153). Isa was administered intravenously at 10 mg/kg weekly for 4 weeks, and every other week thereafter. This preplanned second interim analysis assessed longer term outcomes, including time to next treatment (TTNT), overall survival (OS), time from randomization to disease progression on first subsequent therapy or death (PFS2), and safety.

Results
Pts had a median of 3 prior lines of therapy (IQR 2–4; table). As of Oct 1, 2020 (median follow-up, 35.3 months [mo]), 27 Isa-Pd pts (18%) vs 12 Pd pts (8%) were still on treatment; 60% vs 72% had proceeded to subsequent therapy. Median TTNT was 15.5 mo with Isa-Pd vs 8.9 mo with Pd (hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.42–0.74; P<0.0001); 24% vs 58% of pts with subsequent therapy received daratumumab (dara). Overall response rate (ORR) in subsequent treatment with dara monotherapy was higher after Pd (38%) than Isa-Pd (14%), but was similar (32% vs 31%) with dara combination therapy (table). Median PFS2 in the intent-to-treat population was 17.5 mo with Isa-Pd vs 12.9 mo with Pd (HR 0.76; 95% CI 0.58–0.99; P=0.0202). Median OS was 24.6 mo with Isa-Pd vs 17.7 mo with Pd (HR 0.76; 95% CI 0.58–1.01; one-sided P=0.0280). Median treatment duration was 47.6 weeks (range 1.3–171.6) with Isa-Pd vs 24.0 weeks (range 1.0–168.6) with Pd. Serious treatment-emergent adverse event (TEAEs) were seen in 73% of Isa-Pd pts vs 60% of Pd pts. Most frequent non-hematologic TEAEs (any grade) with Isa-Pd were infusion reaction (38%), upper respiratory tract infection (34%), and diarrhea (30%). Grade 3–4 neutropenia (85% vs 71%) and thrombocytopenia (34% vs 25%) were more frequent with Isa-Pd than with Pd.

Conclusion
Isa-Pd demonstrates a significant improvement in TTNT and PFS2 compared with Pd. A strong trend in OS benefit was also seen in the Isa-Pd arm, with approximately 7 mo improvement in median OS. The overall safety profile remains unchanged from prior analyses.

Keyword(s): CD38, Monoclonal antibody, Multiple myeloma, Phase III

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