The GMMG-HD7 trial is a randomised trial, phase III trial, involving over 60 sites throughout Germany.
The trial has two randomisations: in the first randomisation we compare induction treatment with six
three-week cycles of lenalidomide, bortezomib and dexamethasone, referred to as RVd, compared to
RVd plus isatuximab. The primary endpoint of this part of the study is the rate of minimal residual
disease negativity by next generation flow cytometry at a sensitivity of 10 -5 . Thereafter, patients
receive standard intensification and high dose melphalan, 200mg/m 2 , and autologous stem cell
transplantation.
Next, they get randomised, again in a 1:1 ratio, either to receive lenalidomide maintenance or
lenalidomide plus isatuximab. The endpoint of the second part of the study will be progression free
survival from second randomisation.
What were the key findings?
We just presented and analysed the first part of the study which aimed at the comparison of MRD
negativity by NGF at the end of induction therapy, comparing isa-RVd versus RVd alone. The key
finding of the study is that the MRD rates were significantly higher with the use of isa-RVd versus RVd
alone. The MRD rates were 50.2% versus 35.6% with an odds ratio of 1.82, highly significantly
favouring isa-RVd.
As a secondary endpoint we looked at the outcomes of complete response rates which did not differ
yet, likely due to the long half-life time of the M-protein. As other endpoints we looked at the rates of
very good partial response or better after induction therapy and these were also highly significantly
increased with the use of isa-RVd versus RVd alone. The rates of vgPR or better were 77% versus
61% in isa-RVd versus RVd alone.
What did you see in terms of safety?
The safety profile in the study was very good. With the addition of isatuximab to RVd we did not
observe any new safety signals. The overall rate of treatment emergent adverse events was similar
between the two induction therapy regimens, as was the rate of severe adverse events. Beyond that,
we observed a higher rate of neutropenia with the use of isa-RVd versus RVd but this did not
translate into a higher rate of severe infections during induction therapy. Also, more patients in the
isa-RVd versus RVd arm completed the full six cycles of induction therapy.
What impact do you think these results could have?
These results are very important to the community since they confirm that isatuximab RVd has the
potential to further increase the rates of MRD negativity in this very early treatment phase and
probably also beyond. So in 2023 we will look at the post-transplant outcome data and also at the
progression free survival data and there we hope to see the data maturing.
What is the overall take away?
Together with the CASSIOPEIA trial and the GRIFFIN trial, the GMMG-HD7 trial supports the
rationale that CD38 monoclonal antibodies will be the new standard of care, together with an IMiD
and a proteasome inhibitor for transplant eligible patients with newly diagnosed multiple myeloma in
the induction therapy. Of course, we are looking forward, since the GMMG-HD7 trial is ongoing, to
see the results – whether the addition of isatuximab to lenalidomide during maintenance yields
additional benefit for the patients.
