Rapid Readouts: IKEMA Subgroup Analysis in Relapsed Multiple Myeloma Patients With High-Risk Cytogenetics

Timothy Schmidt, MD, discusses data from the following presentation:

• Subgroup analysis of the phase 3 IKEMA study of isatuximab plus carfilzomib and dexamethasone in patients with relapsed multiple myeloma and high-risk cytogenetics. (Spicka I, et al. ASCO 2021; June 4–8, 2021)
  • An interim analysis of the phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab-carfilzomib-dexamethasone significantly improved progression-free survival (PFS) compared with carfilzomib-dexamethasone in patients with relapsed multiple myeloma (HR 0.531; 99% CI, 0.318–0.889; P = .0007), with a manageable safety profile.
  • This subgroup analysis of IKEMA examined efficacy and safety in patients with high-risk cytogenetics [t(4;14), del(17p), and t(14;16) and/or gain(1q21)].
  • Patients with 1 to 3 prior lines of therapy were randomized 3:2 to receive isatuximab-carfilzomib-dexamethasone (n = 179) or carfilzomib-dexamethasone (n = 123). High-risk cytogenetics was assessed by central laboratory analysis and defined as ≥1 of the following: del(17p): 50% cutoff; t(4;14) or t(14;16): 30% cutoff. Assessment of gain(1q21) was prespecified as ≥3 copies: 30% cutoff.
  • Primary end point was PFS. Secondary end points were response rate, minimal residual disease (MRD) negativity rate, and safety.
  • Of the randomized patients, 23.5% isatuximab-carfilzomib-dexamethasone and 25.2% carfilzomib-dexamethasone had ≥1 high-risk cytogenetic abnormality (CA); 26.3% isatuximab-carfilzomib-dexamethasone and 25.2% carfilzomib- dexamethasone had isolated gain(1q21).
  • Efficacy results:
    • The addition of isatuximab to carfilzomib-dexamethasoneimproved PFS, compared with carfilzomib-dexamethasonealone, for patients with ≥1 high-risk cytogenetic abnormality and standard-risk patients.
    • Patients with t(4;14) (HR 0.549; 95% CI, 0.232–1.301) had a more pronounced treatment effect than patients with del(17p) (HR 0.837; 95% CI, 0.281–2.496).
    • A clear PFS benefit with isatuximab-carfilzomib-dexamethasoneover carfilzomib-dexamethasonewas also seen for patients with isolated gain(1q21) and gain(1q21) combined with other high-risk cytogenetic abnormalities.
    • The trend toward improved complete response, ≥very good partial response, and MRD-negativity rates with the addition of isatuximab was more pronounced in patients with gain(1q21) than in patients with high-risk cytogenetic abnormalities alone.
  • Safety results:
    • Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with isatuximab-carfilzomib-dexamethasone vs carfilzomib-dexamethasone, but the incidence of serious and fatal TEAEs was similar with both arms for high-risk patients.
  • The addition of isatuximab to carfilzomib-dexamethasone improved PFS in patients with high-risk cytogenetic abnormalities and disease response in patients with gain(1q21) isolated or combined with high-risk cytogenetic abnormalities, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA population. Isatuximab-carfilzomib-dexamethasone is a potential new treatment option for the difficult-to-treat subgroup of patients with relapsed multiple myeloma and high-risk cytogenetics.