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Clinical Trial
. 2023 May 9;13(1):72.
doi: 10.1038/s41408-023-00797-8.

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study

Thomas Martin #  1 , Meletios-Athanasios Dimopoulos  2 , Joseph Mikhael  3 , Kwee Yong  4 , Marcelo Capra  5 , Thierry Facon  6 , Roman Hajek  7 , Ivan Špička  8 , Ross Baker  9 , Kihyun Kim  10 , Gracia Martinez  11 , Chang-Ki Min  12 , Ludek Pour  13 , Xavier Leleu  14 , Albert Oriol  15 , Youngil Koh  16 , Kenshi Suzuki  17 , France Casca  18 , Sandrine Macé  19 , Marie-Laure Risse  20 , Philippe Moreau #  21
Affiliations
Clinical Trial

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study

Thomas Martin et al. Blood Cancer J. .

Erratum in

Abstract

Longer-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 trial IKEMA (NCT03275285), in a prespecified, follow-up analysis of progression-free survival (PFS, primary study endpoint), final complete response (CR) using Hydrashift Isa immunofixation assay, minimal residual disease (MRD) negativity, and safety. Enrolled patients had relapsed/refractory multiple myeloma (1-3 prior treatment lines). Isa 10 mg/kg was administered intravenously weekly in cycle 1 then biweekly. Efficacy analyses were performed in the intent-to-treat population (Isa-Kd: n = 179, Kd: n = 123) and safety evaluated in treated patients (Isa-Kd: n = 177, Kd: n = 122). Consistent with the primary interim analysis, the addition of Isa to Kd prolonged PFS (HR 0.58, 95.4% CI: 0.42-0.79; median PFS 35.7 [95% CI: 25.8-44.0] vs 19.2 [95% CI: 15.8-25.0] months). PFS benefit was observed with Isa-Kd across subgroups, including patients with poor prognosis. The stringent CR/CR rate was 44.1% vs 28.5% (odds-ratio: 2.09, 95% CI: 1.26-3.48), the MRD negativity rate 33.5% vs 15.4% (odds-ratio: 2.78, 95% CI: 1.55-4.99) and the MRD negativity CR rate 26.3% vs 12.2%, with Isa-Kd vs Kd. The safety profile of Isa-Kd was similar to that reported in the prior interim analysis. These findings further support Isa-Kd as a standard-of-care treatment for relapsed multiple myeloma patients.Clinical trial information: ClinicalTrials.gov, NCT03275285.

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Conflict of interest statement

TM: research funding (to institution) from Sanofi; participation on a steering committee for Sanofi. M-AD: participation in advisory boards for Amgen, BeiGene, Bristol Myers Squibb, Janssen, and Takeda. JM: honoraria from Amgen, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, and Takeda. KY: research funding from Bristol Myers Squibb, Janssen, and Sanofi; honoraria and travel support from Amgen, Sanofi, and Takeda; participation on an advisory board or steering committee for Janssen and Sanofi. MC: participation in speaker’s bureau for Amgen, Janssen, and Sanofi. TF: participation on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, Janssen, Karyopharm, Oncopeptides, Roche, and Sanofi; speakers’ bureau for Bristol Myers Squibb and Janssen. RH: honoraria and consulting/advisory role for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, PharmaMar, and Takeda; research funding (to institution) from Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, and Takeda; participation on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, GSK, Janssen, Oncopeptides, Sanofi, and Takeda; support for attending meetings and/or travel from Amgen, Celgene, Janssen, and Takeda. IŠ: research funding, honoraria, and participation on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, Celgene, Janssen-Cilag, Novartis, PharmaMar, Sanofi, and Takeda. RB: research funding from AbbVie, Acerta Pharma, Alexion, Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CSL Behring, Daiichi Sankyo, Janssen-Cilag, MorphoSys, Pfizer, Rigel Pharmaceuticals, Roche, Sanofi, and Takeda; honoraria from Bayer; consulting or advisory role for Janssen-Cilag and Roche; speaker’s bureau for Bayer. KK: research funding from Bristol Myers Squibb and Janssen. GM: nothing to disclose. C-KM: nothing to disclose. LP: nothing to disclose. XL: nothing to disclose. AO: honoraria from Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, and Sanofi; participation on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, and Sanofi. YK: nothing to disclose. KS: honoraria from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, Ono Pharmaceutical, Sanofi, and Takeda. FC: employed by Ividata Life Science, contracted by Sanofi. SM: employed by Sanofi; may hold stock and/or stock options. M-LR: employed by Sanofi; may hold stock and/or stock options. PM: honoraria and consulting/advisory role for AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Roche, and Sanofi.

Figures

Fig. 1
Fig. 1. Patient disposition.
d dexamethasone, Isa isatuximab, K carfilzomib.
Fig. 2
Fig. 2. Updated PFS with Isa-Kd vs Kd (ITT population).
CI confidence interval, d dexamethasone, HR hazard ratio, Isa isatuximab, ITT intent to treat, K carfilzomib, mPFS median progression-free survival.
Fig. 3
Fig. 3. Subgroup analyses of PFS with Isa-Kd vs Kd.
CI confidence interval, d dexamethasone, eGFR estimated glomerular filtration rate, IMiD immunomodulatory drug, IRT Interactive Response Technology, Isa isatuximab, ISS international staging system, K carfilzomib, MDRD modification of diet in renal disease equation, PFS progression-free survival, PI proteasome inhibitor. *Prior treatment=last prior anti-myeloma regimen.
Fig. 4
Fig. 4. Best overall responses per IRC and MRD negativity rates with Isa-Kd vs Kd (ITT population).
A Best overall responses, and B MRD negativity rates. CR complete response, d dexamethasone, IRC independent response committee, Isa isatuximab, ITT intent to treat, K carfilzomib, MRD minimal residual disease, neg negativity, NGS next-generation sequencing, ORR overall response rate, sCR stringent complete response, VGPR very good partial response.
Fig. 5
Fig. 5. Time to next treatment and PFS2a (ITT population).
A Time to next treatment and B PFS2. CI confidence interval, d dexamethasone, HR hazard ratio, Isa isatuximab, ITT intent to treat, K carfilzomib, mPFS median progression-free survival, NC not calculable, TTNT time to next treatment. aPFS2 was defined as the time from randomization to disease progression on next-line treatment or death, whichever occurred first.
See this image and copyright information in PMC

References

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