Phase 3 ICARIA-MM trial, showing promising efficacy and safety for isatuximab in combination with pomalidomide and low-dose dexamethasone in relapsed/refractory MM.
Isatuximab, which is a CD38 targeting antibody.
It is different from daratumumab, because it has a different isotope for binding.
As a monotherapy, response rates are comparable to what we see with daratumumab.
IT requires a short infusion time and relatively limited pre‑med.
Because it activates compliment to a lesser degree it has a favorable tolerability profile.
The rates of infusion reactions are quite low.
ICARIA trial revealed the combination with isatuximab combined with pomalidomide, showed an impressive response rate in relapsed/refractory patients.
Isatuximab is given typically weekly for the first month, and then can be converted onto every 2 weeks thereafter.
Pomalidomide which was given 3 weeks on and 1 week off.
Over 90% of the patients were refractory to lenalidomide.
Associated, essentially with a doubling of PFS.
There was 12‑month median PFS for the 3 drugs, and a six‑month PFS for the 2 drugs.
There was effectively a doubling of response rate from around 35%, to approximately 60% to 70% in the 3-drug combination.
Infusion reactions were low in terms of incidents.
Seeing a trend in favor of overall survival advantage to 3 drugs over the 2.
The use of isatuximab early in the relapsed/refractory course conferred trend favoring survival.
Approved in combination of carfilzomib and dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.
Approved with addition of isatuximab to the combination of carfilzomib and dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy,.
The anti-CD38 treatment of choice for patients with relapsed or refractory multiple myeloma.
Phase 3 IKEMA trial showed that the triplet reduced the risk of disease progression or death by 45% vs Kd alone in this patient population.
The median progression-free survival had not yet been reached with the isatuximab combination.
No statistically significant difference in objective response rate was observed with the triplet vs the doublet, at 86.6% vs 82.9%, respectively; complete response rates were 39.7% vs 27.6%, respectively
Most common adverse events; respiratory tract infection, infusion-related reactions, fatigue. hypertension, diarrhea, pneumonia, dyspnea, and cough
Serious AEs in the isatuximab combination: were pneumonia and upper respiratory tract infections.
The addition of Sarclisa to carfilzomib and dexamethasone reduced risk of disease progression or death by 45%.
The study reinforces the potential for isatuximab to become a standard of care in relapsed or refractory multiple myeloma.