Isatuximab-Kd shows consistent efficacy across RMM patient subgroups

Audrey Abella
07 Jul 2021
Findings from subgroup analyses of the IKEMA trial presented at EHA 2021 aligned with those observed in the overall analysis, further validating the benefits of the isatuximab + carfilzomib-dexamethasone (Isa-Kd) combination regimen for relapsed multiple myeloma (RMM).
 
In the prespecified interim efficacy analysis, progression-free survival (PFS) substantially improved with Isa-Kd vs Kd (hazard ratio [HR], 0.53; p=0.0007). There were also deeper responses with Isa-Kd vs Kd as reflected by the rates of complete response (CR; 40 percent vs 28 percent), ≥VGPR* (73 percent vs 56 percent), and minimal residual disease negativity rate (MRD–; 30 percent vs 13 percent). [Lancet 2021;397:2361-2371]
 
IKEMA comprised 302 patients who had 1–3 prior lines of therapy, no prior carfilzomib exposure, and were nonrefractory to prior anti-CD38 therapy. Participants were randomized 3:2 to receive either Isa-Kd or Kd. Isatuximab 10 mg/kg IV was given weekly for 4 weeks, then every 2 weeks. Carfilzomib (20 mg/m² [days 1–2] then 56 mg/m² for all subsequent cycles) and dexamethasone 20 mg were administered twice weekly.
 
Elderly patients
Among participants aged ≥70 years (28 percent of the overall cohort), the Isa-Kd regimen led to PFS improvements (HR, 0.36), as well as numerically higher CR (38 percent vs 24 percent), ≥VGPR (73 percent vs 56 percent), and MRD– rates (23 percent vs 12 percent) compared with Kd. [EHA 2021, abstract EP980]
 
“[These findings show that] the addition of Isa to Kd improved PFS and quality of response in elderly patients,” said the researchers.
 
High-risk cytogenetics
In the analysis evaluating patients with high-risk cytogenetics** [24 percent of the overall cohort had ≥1 high-risk cytogenetic abnormality (CA); 26 percent had isolated gain(1q21)], a PFS benefit with Isa-Kd was seen in patients with high-risk CA and gain(1q21) plus other high-risk CAs (HRs, 0.72 and 0.68, respectively). The PFS benefit was more pronounced in patients with isolated gain(1q21) (HR, 0.46). [EHA 2021, abstract EP981]
 
Isa-Kd recipients with gain(1q21) also had deeper responses than patients with high-risk CA (47 percent vs 24 percent [CR], 81 percent vs 57 percent [≥VGPR], and 36 percent vs 21 percent [MRD–]), further validating the efficacy of Isa-Kd in a difficult-to-treat patient subgroup.
 
Pretreated patients
Another analysis looked at patients who had prior treatments. Fifty-five percent of the overall cohort had >1 prior line of therapy; the rest only had one. Thirty-three percent were refractory to lenalidomide, while 30 percent were refractory to bortezomib. [EHA 2021, abstract EP986]
 
A clear PFS benefit was seen with Isa-Kd vs Kd across all subgroups, be it among those who received one or >1 prior line (HRs, 0.59 and 0.48, respectively) or those who were lenalidomide- or bortezomib-refractory (HRs, 0.60 and 0.62, respectively).
 
Isa-Kd also generated numerically better depths of response than Kd across all subpopulations, most notably among those who had >1 prior line of therapy (38 percent vs 21 percent [CR], 71 percent vs 52 percent [≥VGPR], and 26 percent vs 9 percent [MRD–]) and lenalidomide-refractory patients (39 percent vs 12 percent, 67 percent vs 36 percent, and 25 percent vs 10 percent, respectively).
 
“Patients with MM often relapse and become refractory to successive lines of therapy, warranting better treatment options … [Our findings show that Isa-Kd] improved PFS and depth of response [regardless] of prior lines of therapy or refractory status,” said the researchers.
 
Taken together, these findings reflect the benefits of adding isatuximab to carfilzomib-dexamethasone and support the interim efficacy findings, corroborating the potential of Isa-Kd as a new standard of care in this patient setting.
 
 
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