ASH 2023 | Dual-targeting of Slamf-7 and CD38 with elotuzumab and isatuximab in multiple myeloma

So as we navigate this revolution of immunotherapy in multiple myeloma, the theme of dual-targeting has really come to the surface. And this has been explored with bispecific T-cell engagers targeting both BCMA and GPRC5D. But we have to remember that we have a prior generation of immunotherapy with naked monoclonal antibodies that target CD38 or Slamf-7 that up to this point had not been combined on a single regimen. The trials that led to the clinical data that supports the use of those antibodies, they usually did not include patients who had received the other antibody previously, and no trial has been done that combined both. So we have now data, for example, for elotuzumab, pomalidomide and dexamethasone. We have data for isatuximab, pomalidomide and dexamethasone. And this approach was why not combine both. You can have an additive effect by dual targeting. But there’s also a very intricate and robust hypothesis of how the use of the anti-Slamf-7 antibody might potentiate the anti-CD38 antibody and vice versa.

So my colleague from the Medical College of Wisconsin, Doctor Dhakal, started within our COMET consortium this multi-institutional trial that had a dose finding, a safety leading, of the combination of both monoclonal antibodies with pomalidomide and dexamethasone on patients with two or more prior lines of therapy and prior lenalidomide refractory. So that’s a very hard population to treat. And this trial is ongoing. And what he reported at this meeting was the safety leading. And the good news is the regimen is well-tolerated and no safety events. And the responses were 80%, which is very high, particularly if you consider a subset of those patients who had received prior CD38 monoclonal antibody because that was allowed on the protocol, and those who are anti-CD38 antibody not previously exposed, the response rate was 100%. So I think this is very thought provoking, and we look forward to continue to accrue to this trial and see this data mature, to see if that is really an avenue for combination of monoclonal antibodies in combination with pomalidomide.