Sarclisa plus Kyprolis found to stop cancer for nearly 3 years in trial
Combo delayed cancer progression in relapsed and hard-to-treat cases
Sarclisa (isatuximab), given on top of standard treatment with Kyprolis (carfilzomib) and the steroid dexamethasone, was found to delay disease progression by almost three years, on average, in people with relapsed or refractory — hard-to-treat — multiple myeloma, according to updated data from a Phase 3 clinical trial.
These results corresponded to a 1.5-year extension in the time patients lived without cancer progression relative to those given the standard treatment alone.
Overall, the findings show that the triple combo significantly delayed disease progression or death in this patient population over the longer term — similar to previously announced interim results that spanned about 1.5 years altogether.
The new results were reported in the study, “Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study,” published in the Blood Cancer Journal. The work was funded by Sanofi, which markets Sarclisa, and was involved in the study’s design, analysis, and data interpretation.
Earlier results supported triple combo’s approval in US, EU and Japan
Sarclisa is an antibody-based therapy that works by targeting the CD38 protein on myeloma cells, triggering these cells’ destruction.
In the U.S. and elsewhere, Sarclisa was originally approved for use in combination with Pomalyst (pomalidomide), an immunomodulatory agent, and the dexamethasone steroid. That combo was designed to treat adults with relapsed or refractory multiple myeloma (RRMM) who had tried at least two prior lines of therapy.
The Phase 3 IKEMA clinical trial (NCT03275285), launched in 2017, tested whether adding Sarclisa to the proteasome inhibitor Kyprolis and dexamethasone provided benefits to RRMM patients who had received 1-3 three lines of treatment.
The study enrolled 302 patients, who were randomly assigned to receive either the triple combination or Kyprolis and dexamethasone alone — dubbed the Kd regimen. The median age of participants in the triple combo group was 65; it was two fewer years, or a mean age of 63, in the Kd group. Most patients had received at least two prior lines of treatment, and about 1 in 4 had high-risk disease based on genetic markers.
The results of the trial’s preplanned interim analysis, at about 1.5 years of follow-up, showed that the triple combo significantly delayed disease progression or death by about 40% relative to the Kd regimen.
Those findings, announced in 2020, supported the triple combo’s approval in the U.S. for RRMM patients after one to three prior lines of therapy. The results also supported approvals in Europe, for patients with relapsed myeloma after at least one previous therapy, and in Japan, for RRMM patients.
New data show longer-term outcomes of IKEMA study
Now, researchers have reported the results of another preplanned analysis, this one of longer-term outcomes among the IKEMA participants. The main goal was to assess group differences in terms of progression-free survival, known as PFS. The term refers to time spent still alive, without signs of cancer progression.
For the triple combo group, the median treatment duration was longer as compared with the Kd regimen group. Specifically, treatment lasted for nearly two years for those on the combination therapy versus a little longer than one year for those on the Kd regimen.
The median follow-up time was 44 months, or a little longer than 3.5 years. Among patients, the median PFS time was 35.7 months, or just shy of three years, for the Sarclisa-treated patients, compared with 19.2 months, or a little longer than 1.5 years, in patients given the Kd regimen.
This is “the longest PFS reported to date with a [proteasome inhibitor-based] regimen in the relapsed [multiple myeloma] setting,” the researchers wrote.
Statistical analyses indicated that adding Sarclisa to Kyprolis and dexamethasone significantly lowered the risk of disease progression or death by about 42%.
More patients given combo saw a complete response during trial
Further analyses showed consistent results across all patient subgroups, including those with a poor prognosis. Such patients included the elderly, those with reduced kidney function, and individuals high-risk disease based on genetic analyses.
The overall response rate — that is, the proportion of patients who experienced a partial or complete reduction in cancer burden — was comparable among patients given Sarclisa or not (86.6% and 83.7%, respectively).
However, a significantly greater proportion of patients on the triple combo achieved a complete response or stringent complete response, meaning no detectable cancer, relative to those on the Kd regimen (44.1% vs. 28.5%).
No minimal residual disease (MRD) was significantly more common among patients given Sarclisa (33.5% vs. 15.4%), as was the absence of the small number of cancer cells that sometimes remain after treatment. Those remaining cancer cells can, in some cases, drive disease relapse and progression.
Similar results were observed for the proportion of patients showing complete response and no MRD (26.3% vs. 12.2%).
These findings further support [Sarclisa plus Kyprolis and dexamethasone] as a standard-of-care treatment for relapsed multiple myeloma patients.
The MRD-related superiority of the Sarclisa combo over the Kd regimen was seen across patient subgroups.
In addition, fewer patients given Sarclisa had gone on to receive further myeloma treatments compared with those given the Kd regimen (44.1% vs. 64.2%).
In this updated analysis, overall survival outcomes generally favored patients given Sarclisa. However, the trend did not reach statistical significance. The researchers noted that comprehensive overall survival analyses are planned for this year.
Safety data from this updated analysis were consistent with the trial’s interim results, and indicated that the addition of Sarclisa did not increase the risk of serious or fatal side effects.
The most commonly reported side effects with the triple combo included infusion reactions (45.8%), diarrhea (39.5%), high blood pressure (37.9%), and upper respiratory tract infections (37.3%). Fatigue also was reported by nearly a third (31.6%) of patients.
“These findings further support [Sarclisa plus Kyprolis and dexamethasone] as a standard-of-care treatment for relapsed multiple myeloma patients,” the researchers wrote.