Suzanne Trudel, MD, on Multiple Myeloma: Results From the DREAMM-8 Study of Treatments After Relapse

We've made a lot of progress for the treatment of myeloma. A lot of this comes from using triplets and quadruplet therapies in newly diagnosed patients with myeloma. We're incorporating the three main classes of anti-myeloma treatments, including proteasome inhibitors, the immunomodulatory drugs, and the anti-CD38 monoclonal antibodies. However, almost uniformly patients relapse and now there's an unmet need in those relapse patients because either the majority of them will be exposed and many will be refractory to the three main classes of drugs we use to treat myeloma. So we really need to look for new treatments that explore new drugs that have novel mechanisms of action. And this is where DREAMM-8 fits in. It tries to address that gap for the patients in first relapse. So DREAMM-8 was a randomized phase three study of belantamab mafodotin, which is an antibody drug conjugate that targets BCMA in combination with pomalidomide and dexamethasone, and it compared it to pomalidomide plus bortezomib and dexamethasone, specifically in patients who have relapsed after their first line of therapy that included lenalidomide. So a total of 302 patients were accrued to the study. 155 got randomized to the study arm, which was the belantamab mafodotin plus pomalidomide and dexamethasone, or we call it BPD or Bela-Pd. 147 got randomized, the control arm of pomalidomide plus bortezomib and dexamethasone. And the primary endpoint of the study was progression-free survival, but then we had other key secondary endpoints including overall survival, duration of response and MRD negativity rate. At a medium follow-up of 21.8 months the study met its primary endpoint of progression-free survival with progression-free survival not reached in the patients who were on the Bela-Pd arm and 12.7 months for the patients who received PVD. A 12 month PFS was 71% versus 51% for Bela-Pd versus PVD. And this really represents a clinically meaningful and statistically significant reduction, the risk of death by 48%. And we see from the Kaplan-Meier plots that the curbs separate early and remained sustained in favor of the Bela-Pd combination. We then also performed a subgroup analysis, and we see that the PFS benefit for belamaf was consistent across all the pre-specified subgroups. So this combination appears to benefit patients who have high risk disease, those patients who have relapsed after lenalidomide and our lenalidomide refractory, those that also are refractory to anti-CD38 monoclonal antibodies. So in addition to the progression-free survival benefit in favor of the belamaf-Pd, all the other secondary endpoints were also favoring the bela-Pd combination. This includes the rate of complete response, the MRD negativity rate at 10 to the minus 5 progression free survival too. And although the overall survival data is immature at this point in time, again overall survival favored belamaf plus Pd with a hazard ratio of 0.77. Now, when we look at the safety profile, essentially the toxicities that we observed were consistent with what we expect for the individual drugs in the combination. The most common adverse events were ocular toxicities, which are well described for MMAF containing ADCs, which is what belamaf is, and it's important to note with protocol pre-specified dose modifications, including dose interruptions and dose reduction there was a low discontinuation rate from the belamaf arm at 9%. The majority of ocular events were reversible with these modifications. So just in summary, really this represents a new treatment option for patients who have relapsed after one prior line of therapy and are lenalidomide exposed where there really is a gap in treatment at the present time with our currently available options.