Isatuximab in combination with pomalidomide and dexamethasone shows promising efficacy in 2nd line RRMM

Prof Evangelos Terpos - University of Athens, School of Medicine, Athens, Greece

As we know, the combination of isatuximab, pomalidomide and dexamethasone has been licensed for the treatment of patients with relapsed/refractory multiple myeloma who have received at least two prior lines of therapy. So based on this background we wanted to see what would be the effect of this combination in patients who had received only one prior line of therapy, especially in those who had been exposed to lenalidomide and the majority of them are refractory to lenalidomide.

So we scheduled a study where isatuximab, pomalidomide and dexamethasone is given to patients who received one prior line of therapy and all of them had been exposed to lenalidomide. Also in this study we have a unique opportunity to have a randomisation after the achievement of very good partial response in the patients to have isatuximab at the standard dose of every 15 days versus isatuximab given monthly. I think this is also a very important part of the study as this is the only study that, let’s say, compares the twice monthly versus once monthly isatuximab doses.

What were the results of this study?

First of all, the study is going to include 108 patients in order to meet the statistical power. Now we present the first data in the first 30 patients who have been included in the study. We have seen with the combination of isatuximab, pomalidomide and dexamethasone a high response rate of around 75% and almost one third of these patients have achieved a VGPR only within 8 months of median follow-up. This is also the primary endpoint of the study – what is the overall response rate within 6 months of therapy.

These patients now are randomised, the VGPR patients, to receive isatuximab every month once per month or every 15 days. At the end of the study we are going to have very interesting results.

The safety is very good, we don’t see anything more than what we expected from the combination of isatuximab/pomalidomide/dexamethasone and it’s mainly due to pomalidomide like neutropenia, which is the most common adverse event of this study.

What is the impact and significance of these results?

First of all, what we have seen to date for patients who are refractory to lenalidomide or have been exposed to lenalidomide, which is the vast majority of patients at first line, isatuximab/pomalidomide/dexamethasone seems to be a very good combination for second-line therapy that offers a very good VGPR rate. We want also to check if we can have something like a maintenance phase with isatuximab, pomalidomide and dexamethasone, giving isatuximab every month in order to reduce the burden of the patients to come to the hospital twice per month.

Where does the study sit in the treatment landscape?

Patients who are eligible for transplant are receiving a quadruplet now combination with dara-VTd or dara-VRd followed by transplant and lenalidomide maintenance. So at the time of progression the majority of the patients are lenalidomide refractory. So I believe some years before the induction treatment included only VRd, for example, so all these patients now that they have started to progress they have limited options, I would say. Isatuximab/ pomalidomide/dexamethasone is a very good combination for these patients and we want to further explore its efficacy in patients who are lenalidomide exposed and especially refractory.

What is next for this study?

We want to, of course, finish recruitment of the study with 100 patients. We have some difficulties now because the study excludes patients who have been exposed to daratumumab or isatuximab in the first line but now we are going to amend the protocol and include patients who have received, for example, induction therapy with either daratumumab or isatuximab before transplant. If we have a washout period of an anti-CD38 monoclonal antibody of 12 months then these patients would be allowed to participate in the study. So this would be the first amendment.

The second would be after some very encouraging data that we have for isatuximab infusion rate of 30 minutes only, we are also going to amend our protocol and give the isatuximab in a 30-minute infusion in order to reduce also the time that the patient is at the hospital.

So with these two amendments I think that we are going to have very good results and our study will be more up-to-date with first-line treatment.

Is there anything else you’d like to add?

No, with this study we are going to have a good result for patients now who are receiving daratumumab-VTd or -VRd up front, for example, for four cycles or for six cycles and then they receive lenalidomide maintenance and we will provide what isatuximab/pomalidomide /dexamethasone can do in these patients in order to have an alternative to the other treatment options that the patients have, for example, isa-Kd or dara-Kd which is the most in use in this patient population regimens. Sometimes because of cardiac problems carfilzomib cannot be used. So that will give a good answer to the doctors and the patients in order to know if isatuximab/pomalidomide/dexamethasone can be used and how often to these patients.