EHA 2023 | MagnetisMM-3 extended follow up results: elranatamab monotherapy in R/R multiple myeloma

So during this EHA 2023, we presented the updated results, with longer follow-up, of the MagnetisMM-3 Phase II open-label, international, prospective trial in relapsed/refractory multiple myeloma. And this is a trial testing the use of a bispecific antibody, namely elranatamab, which is directed against BCMA and CD3.

So, the cohort included 123 patients who received a median of five prior lines of therapies. 25% of the patients were high-risk cytogenetics and more than 30% had extramedullary disease – so a very high-risk population. All of them were exposed to immense proteasome inhibitors with also anti-CD38 monoclonal antibodies, and almost the majority, 95%+, were refractory to the last line of therapy. And today, with a follow-up of around 15 months we can see more than 60% response. And the most important piece of information is about 35% more than CR, which is clearly unprecedented when it comes to such a heavily pretreated, highly advanced multiple myeloma population. And such deep response illustrates the power of immune therapy and how bispecific antibodies can allow us to harness this immune-mediated anti-tumor anti-myeloma effect. And actually, this is translating into a very nice progression-free survival – the median PFS is not yet reached, and actually when you look to those patients who are in CR, actually it is around 90%, almost 89%+ PFS at 15 months, which is again quite amazing in such population.

And you can achieve all of these excellent results, I would say, with very good safety profile because the setup step-up dosage of elranatamab allows to reduce the incidence of severe cytokine release syndrome, neurotoxicity, and the rate of infectious complications remains moderate –  majority of Covid 19 actually infections, which we hope will not be a big matter of concern in the near future. But also, one important piece of information is that those patients, 50+ patients, who were able to respond but also to go beyond six months and actually, where the protocol allowed, to switch into a twice-monthly administration, so every 15 days, actually here, 80% of these patients are going to maintain the response rate, which is quite, very good. And also you can see a clear tendency towards decreasing incidence of opportunistic infections.

So to make a long story short, in summary, this long follow-up of the MagnetisMM-3, the first cohort of 123 patients, clearly demonstrates the efficacy with a deep response – 35% CR, PFS unprecedented, excellent safety profile and, most importantly, you can decrease the frequency of administration into every 15 days. And this is providing the foundation, I would say, to continue the development of elranatamab, which is likely to become a backbone of the future, different treatments of multiple myeloma. And this is part of the bigger picture about the advent of immune therapies in multiple myeloma, whether cellular therapies like CAR-T cells, and there are some exciting data there, but also the different bispecific antibodies, whether against BCMA, whether against GPRC5D or FCRH5 – but even bispecific antibodies against CD38, because we usually always speak about anti-CD38 monoclonal antibodies, but now there are other bispecific antibodies developed against CD38.

So overall it is an exciting era for immune therapy in multiple myeloma and I believe this is going to contribute towards further increasing the survival of many patients. So probably a lot of these patients, thanks to the different available options now are likely to live long and well.