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KarMMa-3

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma (KarMMa-3)

Phase 3N = 386NCT03651128

Population
Relapsed and refractory myeloma after two to four previous regimens (immunomodulatory agents, proteasome inhibitors, daratumumab), refractory to the last regimen; 66% triple-class refractory and 95% daratumumab refractory.
Design
International, open-label phase 3 trial: 386 patients were randomly assigned 2:1 to ide-cel (150 to 450 x 10^6 CAR-positive T cells) or one of five standard regimens. The primary end point was progression-free survival; key secondary end points were overall response and overall survival (immature at this analysis).
Primary endpoint
PFS
Arms
  • Ide-cel (experimental, n = 254): Idecabtagene vicleucel, 150 to 450 x 10^6 CAR+ T cells
  • Standard regimens (control, n = 132): One of five standard regimens chosen by the investigator
People
Rodriguez-Otero P
PFSHR 0.49 (95% CI 0.38–0.65)Δ median PFS+8.9 monthsΔ ORR+29 points
Show the numbers
Results reported for KarMMa-3
EndpointAnalysisIde-celStandard regimensEffect
PFSRandomised patients (386)primarymedian follow-up 18.6 monthsRodriguez-Otero 2023median 13.3 monthsmedian 4.4 monthsHR 0.49 (95% CI 0.38–0.65)P<0.001Grade 3 or 4 adverse events 93% with ide-cel and 75% with standard regimens. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88% (grade 3 or higher in 5%) and investigator-identified neurotoxic effects in 15% (grade 3 or higher in 3%).
ORRRandomised patients (386)primaryRodriguez-Otero 202371%42%P<0.001The abstract reports a complete response in 39% and 5%, respectively. Overall survival data were immature.
Results reported for KarMMa-3
EndpointAnalysisIde-celStandard regimensEffect
PFSRandomised patients (386)primarymedian follow-up 18.6 monthsRodriguez-Otero 2023median 13.3 monthsmedian 4.4 monthsHR 0.49 (95% CI 0.38–0.65)P<0.001Grade 3 or 4 adverse events 93% with ide-cel and 75% with standard regimens. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88% (grade 3 or higher in 5%) and investigator-identified neurotoxic effects in 15% (grade 3 or higher in 3%).
ORRRandomised patients (386)primaryRodriguez-Otero 202371%42%P<0.001The abstract reports a complete response in 39% and 5%, respectively. Overall survival data were immature.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.490.38–0.65
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Ide-cel (experimental)
  • Standard regimens (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsIde-celStandard regimens
0100.0%100.0%
865.9%28.4%
1741.2%6.9%
2527.2%1.9%
3317.9%0.6%
Primary publication: Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023;388(11):1002-1014. PubMedDOI

Appears in

Sources

  1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023;388(11):1002-1014.

    PubMedDOI