Isatuximab shows benefit in transplant-ineligible patients with newly diagnosed multiple myeloma
Prof Thierry Facon - Chu De Lille, Lille, France
The abstract we are presenting at this meeting is a study called IMROZ. IMROZ is a new study, a new phase III international myeloma study, for newly diagnosed transplant ineligible patients with multiple myeloma. The purpose of the study was to assess the clinical benefit of adding isatuximab, which is an anti-CD38 monoclonal antibody, to the standard of care bortezomib, lenalidomide and dexamethasone, also referred as the VRd regimen, which is a very well-established standard of care in this disease.
The population is mainly a population of elderly people. We enrolled patients who are not transplant eligible based on comorbidities or age but we excluded patients over the age of 80 years. It’s important to say that in this population it remains an unmet medical need to a certain extent, especially for the more elderly. So the study had a PFS primary endpoint, so patients were randomly allocated to either isatuximab VRd or VRd alone, followed by continuous treatment with either isa-Rd, isatuximab, lenalidomide and dexamethasone, or lenalidomide and dexamethasone alone.
The primary endpoint of PFS was met. With a median follow-up of five years the median PFS was not reached in the isa-VRd arm and was 54 months, which is quite good, in the VRd arm. So the hazard ratio was 0.59 and the five-year PFS rate was 63% in the isa-VRd arm versus 45% in the VRd arm. So that’s a very strong benefit in terms of PFS. So the addition of isatuximab was able to delay progression in a very important fashion, both from a statistical and a medical point of view.
The isa-VRd arm has also a great benefit in terms of response. We achieved high quality responses in a substantial proportion of patients. For example, 75% of patients in the isatuximab arm achieved at least a complete response versus 64% in the VRd arm. Of course we looked at what we call minimal residual disease, so MRD, and MRD was much more frequent in the isatuximab arm. For example, the MRD negativity in complete responders was 55.5% in the isatuximab arm versus 41% in the VRd arm. And also in terms of what we call sustained MRD negativity, so MRD negativity for more than one year, the incidence was almost double in the isatuximab arm, moving from 24% in the VRd arm versus 47% in the isa-VRd arm.
So survival is still immature, the median follow-up is quite long at five years but the overall survival is still immature but we have a trend in favour of the isa-VRd arm with a hazard ratio of 0.77, representing a 22% reduction in the risk of death.
In terms of safety, nothing was unexpected. Basically the safety profile of the isa-VRd arm was in line with what we know from the safety of each drug. So this regimen was considered to be tolerable for these elderly patients.
At the end of the study our conclusion is to say that for transplant ineligible patients with an age less than 80 years, isatuximab in combination with VRd will become a new standard of care.
What could be the impact of this research?
This kind of quadruplet regimen is not only for the younger patients, the transplant eligible patients, but also for some transplant ineligible patients. So this will extend the use of quadruplet regimens, not for all myeloma patients but for the majority of multiple myeloma patients at the time of diagnosis.
