The GMMG-CONCEPT trial is an investigator initiated trial investigating the quadruplet treatment up front with the monoclonal anti-CD38 antibody isatuximab in combination with carfilzomib, lenalidomide and dexamethasone. So the Isa-KRd regimen for high risk patients, both transplant eligible and transplant ineligible, with newly diagnosed myeloma. The high risk definition is based on the FISH analysis with a deletion 17p or t(4,14) or t(14,16) and all patients have to have ISS stage 2 and 3. We also include patients with more than three copies of 1q21.
So patients receive an extended six cycle induction treatment. Those patients transplant eligible undergo high dose melphalan and autologous stem cell transplantation and this is followed then by a four cycle consolidation and a three drug maintenance. Here we reported about the safety run-in phase as the quadruplet regimen was for the first time applicated in this trial. So we had a safety run-in with the first ten patients who were all in arm A so we reported about the results here.
Were there any adverse events or toxicities?
So overall we saw that the regimen is very well tolerated. We have an unsurprisingly slight hematologic toxicity. We saw overall one fever in neutropenia from the non-hematologic toxicities. We had three grade 3 or 4 in the ten patients – one diarrhoea, one cardiac event and one bleeding event, however this was due to a congenital aneurysm so it was not study drug related.
In light of these results, how do you think this could impact clinical practice?
This is one trial also in the context of now other trials running introducing quadruplet regimens in front line treatment of multiple myeloma. We are seeing this strategy as the future strategy of treating myeloma patients as those treatments are extremely well tolerated. Especially when you use carfilzomib as the proteasome inhibitor, like we do, you do not have the peripheral neuropathy any more as a very severe toxicity our myeloma patients are often hampered by and the monoclonal antibodies are very well tolerated with the lenalidomide as the immune modulator. We have a lot of experience in myeloma treatment so this is really the future.
What are the next steps?
The trial includes in total 153 patients and, as of now, we have included 112. So we are making progress in recruitment so we’ll hopefully close the recruitment in the second quarter of 2020. We will now analyse the first roughly 50 patients for an interim analysis about the induction treatment phase and we hopefully will present those data in next year’s conventions.