COMy 2021 | Novel agents for the management of R/R myeloma

Novel agents in myeloma is something very, very interesting and it’s very up-to-date currently. We know that after one or two prior lines of therapy, myeloma patients have already been exposed or even are refractory to the main class of agents we have available, PI, IMiDs and anti-CD therapy with monoclonal antibodies. So we need now more agents, other mechanisms of action to rescue these patients now, after two, three prior lines of therapy.

What are for me the most important one, the most interesting ones. There are some of them approved, and I think here we can focus on selinexor, the export inhibitor, with activity, with around a 30% response rate in heavily pretreated patients, penta-refractory patients, even activity in patients with extramedullary disease. So this is the first one. In fact, it has already been approved by the FDA and we also have it in Europe now.

So the first point or a first mechanism important for multiple myeloma. The second one, I would mention is melflufen. Melflufen is this PDC, peptide-drug conjugate, we have spoken a lot about it, and this is like a clever melphalan, in which melphalan achieves high concentrations inside the tumor cells, and quite specifically inside of the tumor cells. This also has already been approved by the FDA, but recently, in some weeks ago, by the FDA, in combination with dexamethasone, for relapsed/refractory myeloma patients, and now it’s been also combined with daratumumab or with bortezomib and we have good data, with daratumumab based on the ANCHOR study. In fact, the Phase III trial is currently being started.

These are the two ones, and I think these are the ones that have been approved along with the BCMA antibody-drug conjugate, the belantamab, which is the third one, also with activity and with activity in heavily pretreated patients with 30% responses, some of their responses very durable and with the concern of the keratopathy here. But I think could be managed with a dose reduction. So selinexor, melflufen, belantamab, the three ones, the novel ones that have been already approved. There are some other ones coming, which is the novel CELMoDs. CELMoDs are interesting, they are novel IMiDs. Here we have the iberdomide or the CC-92480, both of them with promising efficacy, even activity in extramedullary disease. So a good data for these agents.

And finally, we will see this is more for the future, other agents that could be interesting, and here we have, for instance, agents targeting some specific population of myeloma patients. We have venetoclax. We already know it very well for 11;14 translocation patients. We have the RAS/BRAF inhibitors for patients with abnormalities in these pathways. We have also evaluated MYK preclinically and it could be also interesting for these selected patient population. So I would say that the future is bright for multiple myeloma. We have several novel approvals, very recent approvals, and we would probably have more in the future in months or years.