Recent results suggest that in patients with relapsed multiple myeloma (MM), combination therapy consisting of carfilzomib and dexamethasone (Kd) plus isatuximab is associated with improvements in progression-free survival (PFS) and depth of response.
According to the study authors, led by Philippe Moreau, MD, of University Hospital Hôtel-Dieu in Nantes, France, the benefit of adding immunoglobin (Ig) G1 monoclonal antibody isatuximab to Kd showed the potential to be “a new standard of care” for patients with relapsed MM. Previous findings from the phase III ICARIA-MM study resulted in approval of isatuximab combined with dexamethasone and pomalidomide for the treatment of relapsed and refractory MM in patients who received two or more prior therapies.
In this phase III multicenter, international study by Dr. Moreau and colleagues, researchers compared the isatuximab plus Kd regimen to Kd alone in patients with relapsed/refractory MM who had previously received one to three lines of therapy.
A total of 179 patients were randomized to receive isatuximab plus Kd, while 123 patients were assigned to treatment with Kd alone. Participants in the triplet combination group received intravenous isatuximab 10 mg/kg each week for the first four weeks, and then every two weeks thereafter.
Treatment was continued until either disease progression or unacceptable toxicity occurred. The investigators evaluated rates of PFS over a median study follow-up period of 20.7 months.
The median age of the study population was 64 years. Overall, patients had received a median of two prior lines of therapy. Approximately 44% had received one previous line of therapy, 33% had received two previous lines of therapy, and 23% had received three or more previous lines of therapy.
At the time of data cutoff, median durations of treatment were 80 weeks for the isatuximab group and 61.4 weeks for the control regimen. Both groups received a similar median relative dose intensity of Kd during the study period.
Median PFS was not reached at follow-up for the isatuximab plus Kd arm, while the median PFS for the Kd group was 19.2 months (95% CI 15.77 to not reached). The interim analysis revealed that the addition of isatuximab led to a significantly prolonged PFS compared with only Kd (hazard ratio [HR] = 0.53; 99% CI 0.32–0.89; p=0.0007).
The two-year estimated PFS was 68.9% for the isatuximab arm compared with 45.7% for the control group (HR = 0.58; 99% CI 0.36–0.92; p=0.0010).
In the intention-to-treat cohort, most patients in the isatuximab group and the control group experienced an overall response (87% vs. 83%, respectively; p=0.19). A significantly greater proportion of patients assigned to isatuximab experienced a very good partial response or better (73% vs. 56%; p=0.0011). A higher proportion of patients treated with isatuximab also had a complete response: 40% vs. 28%.
The measurable residual disease negativity rate was significantly greater in patients treated with isatuximab versus those treated with only Kd (30% vs. 13%; p=0.0004).
Approximately 77% of patients in the isatuximab arm and 67% of patients in the control group experienced grade ≥3 treatment-emergent adverse events (TEAEs). Serious TEAEs were reported in 59% of patients randomized to isatuximab compared with 57% patients assigned to Kd.
In addition, 8% of patients in the isatuximab combination group and 14% of patients in the control group experienced TEAEs, which led to treatment discontinuation. Up to 3% of patients in each group experienced fatal TEAEs during the study.
One limitation of this study was the low prevalence of Black patients (3%), mostly because of lower recruitment at U.S.-based sites. The researchers stated that evidence shows these patients derive nearly the same benefits from proteasome inhibitors as patients who are white.
Study authors report relationships with Sanofi, which sponsored this trial.
Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase III trial. Lancet Haematol. 2021;397:2361-2371.