IMW 2021 | Isatuximab short-duration fixed-volume infusion plus VRd for transplant-ineligible myeloma

In this abstract, we are presenting the updated results on the combination of isatuximab, bortezomib, lenalidomide, and dexamethasone for newly diagnosed patients with multiple myeloma that are not eligible for transplantation, or at least that they do not have an immediate intent for autologous stem cell transplantation.

So, we know that quadruplet therapy is now the standard of care for transplant-eligible patients but now we are starting to see or to test if these quadruplets are also feasible for elderly patients. And this is what we are doing here with this combination with an anti-CD38 monoclonal antibody, isatuximab with VRd. So, these patients were initially treated with this isa-VRd in a useful schema. And this was the Part E-A of the study was a weight-based infusion of isatuximab, so the conventional infusion of isatuximab.

What we are now here reporting, is Part B of the study, which is 46 patients that received a fixed-volume infusion of isatuximab. So it’s a different method of preparing an infusion of isatuximab. So, in total, as we said, 73 patients were included in the trial with this combination, but we are now focusing on the 46 with a fixed-volume infusion.

What can we say about this fixed-volume infusion? First, is that if we reduce the infusion duration, so from the, if we compare Part A with the conventional method with Part B with a fixed-volume infusion, we can see from the second and the subsequent infusions, we decrease almost one hour the duration of the infusion. That was two hours for the second infusion and one hour and 20 minutes for the subsequent infusion. So, we clearly shortened the duration of infusion.

The second point was the safety. We can say that this isa-VRd is quite safe. It’s well tolerated with for patients with non-transplant eligible patients with multiple myeloma. The rate of treatment/infusion-related adverse events, treatment-emergent adverse events, was quite low, and we can focus on the grade three and four so non- there are not frequent non-hematologic toxicity. And also, there was quite well-tolerated in terms of hematological toxicity.

So, convenience of short duration of infusion, safe, and finally, of course, we can, we have to speak about the efficacy of the combination. And we can say that this isa-Vrd, this quadruplet, resulted in 90 – almost all patient responded – 98% of the patients responded with 53% of them, that was the primary end point, achieved complete response. Also, we had the opportunity to check the MRD and we see that 50% of the patients more than 50% achieved MRD-negative. So, the rate of the immunophenotypic CR was 42% for these patients.

Only one now, one additional comment that is about the infusion-related reactions. And with them, we were able to decrease also with these fixed-volume infusion and the infusion-related reactions from 52% -most of them, or the majority of them in their first infusion in Part A with the conventional administration – with decrease from, there was, from this, 52 to 22% with a fixed-volume infusion. I have to say that I think with this quadruplet, with this new method of infusion of isatuximab, we have a combination which is convenient for patients, it’s safe for them, and also I think quite effective.