Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
Language English Country England, Great Britain Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial
PubMed
34097854
DOI
10.1016/s0140-6736(21)00592-4
PII: S0140-6736(21)00592-4
Knihovny.cz E-resources
- MeSH
- Anti-Inflammatory Agents therapeutic use MeSH
- Dexamethasone therapeutic use MeSH
- Progression-Free Survival MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Immunologic Factors therapeutic use MeSH
- Administration, Intravenous MeSH
- Drug Therapy, Combination MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma drug therapy MeSH
- Oligopeptides therapeutic use MeSH
- Prospective Studies MeSH
- Recurrence MeSH
- Aged MeSH
- Thalidomide analogs & derivatives therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Anti-Inflammatory Agents MeSH
- carfilzomib MeSH Browser
- Dexamethasone MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Immunologic Factors MeSH
- isatuximab MeSH Browser
- Oligopeptides MeSH
- pomalidomide MeSH Browser
- Thalidomide MeSH
BACKGROUND: Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, open-label study compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma. METHODS: This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple myeloma aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received the approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285. FINDINGS: Between Nov 15, 2017, and March 21, 2019, 302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19·15 months (95% CI 15·77-not reached) in the control group, with a hazard ratio of 0·53 (99% CI 0·32-0·89; one-sided p=0·0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEAEs led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEAEs during study treatment occurred in six (3%) versus four (3%) patients. INTERPRETATION: The addition of isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population. FUNDING: Sanofi. VIDEO ABSTRACT.
Centro Integrado de Hematologia e Oncologia Hospital Mãe de Deus Porto Alegre Brazil
Department of Haematology University College Hospital London UK
Department of Hematology University Hospital Hôtel Dieu Nantes France
Department of Hematology University of California San Francisco San Francisco CA USA
Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
Department of Internal Medicine Seoul National University Hospital Seoul South Korea
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Sao Paolo Brazil
Lille University Hospital Lille France
Myeloma Amyloidosis Center Japanese Red Cross Medical Center Tokyo Japan
Perth Blood Institute Murdoch University Perth WA Australia
Sanofi R and D Chilly Mazarin France
Sanofi R and D Vitry sur Seine France
Service d'Hématologie et Thérapie Cellulaire CHU and CIC Inserm 1402 Poitiers France
The National and Kapodistrian University of Athens Athens Greece
Translational Genomics Research Institute City of Hope Cancer Center Phoenix AZ USA
References provided by Crossref.org
ClinicalTrials.gov
NCT03275285
