I presented a subgroup analysis of the ICARIA study looking at the impact of the addition of isatuximab to pomalidomide dexamethasone in patients with high risk cytogenetic abnormalities, in particular 17p, (4,14) and (14,16) abnormalities. The bottom line of the study is that the benefit in the high risk patients was at least as good as the standard risk patients in terms of overall response and also progression free survival. Interestingly, in the patients with high risk cytogenetic abnormalities the response rate went from around 20% to around 50% and most of the difference is made up of improved depth of response in terms of VGPR rate which went from around 3% to around 30%. As I said earlier, the benefit is at least as significant in the high risk patients as the standard risk patients.
The toxicity profile was similar, so when you add a third agent into a combination you usually associate it with increased toxicities but the infusion reactions are much less than some of the other CD38 antibodies. There was a slight increase in the rate of infections and grade 3 events overall but this didn’t lead to any increase in the number of patients stopping drug. So overall it’s fairly similar in the two different populations.
The main message is, as I said earlier, the patients with high risk cytogenetic abnormalities benefit at least as much as the standard risk patients. Therefore in that area of need population, people with high risk cytogenetic abnormalities, they should be offered an agent like isatuximab if it’s available to try and improve in terms of achieving a response but also progression free survival.