The phase III ICARIA-MM study demonstrated efficacy and safety of isatuximab (Isa) in combination with pomalidomide and dexamethasone (Pom/dex) in patients with relapsed/refractory multiple myeloma. At December’s American Society of Hematology (ASH) virtual meeting, a post-hoc analysis was presented that investigated the impact of patients’ baseline frailty on clinical outcomes and toxicity when receiving Isa-Pom/dex versus Pom/dex alone.
In this exclusive MedPage Today video, Bhagirathbhai Dholaria, MBBS, of Vanderbilt University Medical Center in Nashville, discusses the analysis.
Following is a transcript of his remarks:
I’m going to go over an interesting abstract discussed at the recent ASH medical exposition oncology meeting, virtual meeting for the first time. And the abstract is 1411, it’s a subgroup analysis of ICARIA phase III study, which the results were previously presented at this meeting.
In this study, the investigators randomized relapsed/refractory multiple myeloma patients between the two treatment arms: isatuximab, pomalidomide and dexamethasone versus pomalidomide and dexamethasone. So overall the study schema were very similar to the APOLLO study, which you all know and has now been published in The Lancet, which was daratumumab and pomalidomide and dexamethasone vs Pom/dex. So this is using another monoclonal anti-CD38 agent with Pom and dex. And in this abstract, the investigators asked the question, whether adding a third agent was tolerable in patients who had high comorbidity or were older, or more frail. So this is a subgroup analysis of the ICARIA study looking at the patients with higher comorbidities and frailty.
So what the investigators did is they calculated, is they divided the patient into three groups: fit, intermediate and frail — based on their age, their ECOG performance status, and the baseline Charlson Comorbidity Index. And, looking at the outcome of this study, especially in the frail patient — I would like to focus on them a little bit more because with the myeloma being a disease of older age, we tend to come across these patients more. So it’s always good to know that intensifying the therapy, if it’s tolerable, it is making any difference in outcome of these patients or not. So just focusing on a frail patient, which I don’t know, a quarter of the patients enrolled in this study? Addition of isatuximab, pomalidomide and dexamethasone led to a superior death rate response and better progression free survival. Although when you look at the Kaplan-Meier hazard ratio, the P value was not statistically significant for PFS and overall survival. The PFS benefits was only significant for patients who are just fit or intermediate, not the frail one.
But, kind of going deeper a little bit into the granular detail, the treatment seems to be very well tolerated, actually. Additional isatuximab did not lead to higher rate of discontinuations in the two treatment arms. In fact, when you look at the number of patients who actually discontinued treatment on the study, more patients in the Pom/dex arm actually discontinued the treatment because of either side effects or more because of progression of the disease. So, adding anti-CD38 agent even in a frail, older individual did not lead to higher discontinuation of the treatment because of the side effects. So it kind of translated into a longer duration on treatment.
Certainly looking at the individual side effects, they have a higher degree of neutropenia when isatuximab was added, which is not a surprise, as we saw that with daratumumab also. They were higher in the area of diarrhea and higher in infusion reaction, which we kind of suspect as isatuximab is an IV injection. And there were higher incidents of upper respiratory infections and bronchitis in the treatment arm with isatuximab, Pom/dex compared to Pom/dex. So certainly it’s not a completely benign intervention. And these patients to be monitored very closely for neutropenia and receive appropriate infection prophylaxis.
But in summary, this study results shows that in a subgroup analysis of Isa+Pom/dex versus Pom/dex phase III study, the addition of isatuximab leads to deeper responses. The treatment seems to be tolerated and it did lead to patients being on a treatment for longer duration compared to just Pom/dex. And additional isatuximab did not lead to higher rate of treatment discontinuation compared to just Pom/dex. Thank you.
Source: MedicalNewsToday.com
