IKEMA: isa-Kde vs Kd in relapsed multiple myeloma

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Abstract

VP5-2022: Updated progression-free survival (PFS) and depth of response in IKEMA, a randomized phase III trial of isatuximab, carfilzomib and dexamethasone (Isa-Kd) vs Kd in relapsed multiple myeloma (MM)

Published: May 19, 2022
DOI: https://doi.org/10.1016/j.annonc.2022.04.013
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P. Moreau; M.A.C. Dimopoulos; J. Mikhael; E. Singh; M-L. Risse; T. Martin
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Background

The anti-CD38 antibody Isa in combination with Kd is approved in various countries for patients (pts) with relapsed MM after ≥1 prior therapy, based on primary interim analysis (IA) of the Phase 3 IKEMA study (NCT03275285). Here we report updated efficacy and safety results from IKEMA.

Methods

This prespecified analysis (179 pts randomized to Isa-Kd, 123 to Kd) evaluated PFS (primary endpoint) at 159 PFS events, PFS2, minimal residual disease negativity (MRD-) rate, complete response (CR) rate, MRD- and CR rate in all pts, and safety. Isa 10 mg/kg was given IV weekly for 4 wks and then every 2 wks; Kd (20/56 mg/m²) was administered in both arms.

Results

At cutoff, 49 (27.4%) pts in Isa-Kd and 11 (8.9%) in Kd were still on treatment. On Jan 14, 2022, median follow-up was 44 mo. The PFS update is consistent with the IA results that demonstrated significant benefit in favor of Isa-Kd: HR 0.58 (95.4% CI 0.42–0.79) with median (m) PFS 35.7 vs 19.2 mo in Isa-Kd vs Kd. PFS2 HR was 0.68 (95% CI 0.50–0.94) with mPFS2 47.2 vs 35.6 mo in Isa-Kd vs Kd. With additional follow up and using the Hydrashift Isa immunofixation assay to rule out potential Isa interference in CR determination, final CR rate was 44.1% in Isa-Kd vs 28.5% in Kd. 33.5% pts reached MRD- in Isa-Kd vs 15.4% in Kd. The rate of MRD- CR pts was 26.3% in Isa-Kd vs 12.2% in Kd. Safety profiles in both arms remain consistent with prior IKEMA findings. Serious TEAEs were reported in 70.1% of Isa-Kd pts vs 59.8% in Kd. The most common, any-grade, non-hematologic TEAEs in Isa-Kd were infusion reaction (45.8%), diarrhea (39.5%), hypertension (37.9%), and upper respiratory tract infection (37.3%)

Table: VP5-2022

Efficacy (ITT)
	Isa-Kd n=179	Kd n=123
Median PFS, mo	35.7 (25.8–44.0)	19.2 (15.8–25.0)	HR (95.4% CI) 0.58 (0.42–0.79)
Median PFS2, mo	47.2 (38.1–NC)	35.6 (24.1–40.5)	HR (95% CI) 0.68 (0.50–0.94)
	n (%) 95% CI		odds ratio 95% CI
ORR	155 (86.6) 0.81–0.91	103 (83.7) 0.76–0.90	-
CR rate	79 (44.1) 0.37–0.52	35 (28.5) 0.21–0.37	2.09 1.26–3.48
MRD- rate	60 (33.5) 0.27–0.41	19 (15.4) 0.10–0.23	2.78 1.55–4.99
MRD- and CR rate	47 (26.3) 0.20–0.33	15 (12.2) 0.07–0.19	2.57 1.35–4.88

^{_{CI, confidence interval; HR, hazard ratio; ITT, intent to treat; NC, not calculable; ORR, overall response rate.}}

Conclusions

These results show unprecedented mPFS, CR rate, MRD- and CR rate in a non-lenalidomide regimen, with benefit in subsequent line and a manageable safety profile. Our findings support Isa-Kd as a standard of care treatment for pts with relapsed MM.

Clinical trial identification

NCT03275285.