A New Wave of Progress in The Treatment of Multiple Myeloma: Translating Evidence to Clinical Practice - Episode 8

RRMM: Treatment Options in Early Relapse and in Triple-Class Refractory MM

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Ajai Chari, MD provides an overview of treatment options in patients with multiple myeloma at first relapse and those with triple-refractory disease


Ajai Chari, MD: We now want to talk about relapsed myeloma and incorporating bispecific antibodies into the treatment. I think there’s tremendous excitement in myeloma about T-cell redirections. But just to set the stage a little bit about who these patients are, and before they’re coming to these bispecifics, we have a plethora of randomized phase 3s, all in high-impact New England/Lancet [medical journal] types of papers. And we have Rd [lenalidomide, dexamethasone] backbones. The problem with these is that most patients, as we said, are not going to be Len [lenalidomide] refractory. If we toss those out, we have a plethora of Vd [bortezomib, dexamethasone] backbone studies. These are great, but look at the progression-free survival [PFS] of the Vd control arm in pink; it’s 7 to 11 months. It’s hard to give twice-weekly bortezomib. Whether you intend to do fixed duration, like in the CASTOR [NCT02136134], or treatment to progression, patients don’t tolerate it and it’s not a great backbone on which to build. I think many of us have moved past that. Of course, the BELLINI study (NCT02755597) was really important for 11, 14, and had an unprecedented hazard ratio and PFS of 0.1 and an overall survival [OS] benefit, but not necessarily for all patients. Then we have the next generation Kd [carfilzomib, dexamethasone]-backbone studies, with really cool data for CANDOR (NCT03158688), IKEMA (NCT03275285) and K side dex [dexamethasone]. Now we’re seeing that the Kd-backbone is much better, 15 to 19 months, and on top of that, the addition of a CD38 is giving you a hazard ratio of around 0.6, which is really hard to do. Most importantly, we know that becoming Len refractory actually has shown an inferior prognosis. And we know from CANDOR already that Len refractory patients had a PFS of 28.1 months, which is not different from the overall population. Great backbone; PomDex [pomalidomide plus dexamethasone][is] obviously another option as well. These are slightly different. They’re usually a little more heavily treated and more Len refractory in the Kd studies that we saw. They’re only about a third of patients here, so much higher. The problem here is PomDex as a doublet [therapy] fares relatively poorly; 4 to 7 months. And then the addition of a third agent gives you better results. I think people have been very impressed with the Len refractory Kd, CD38 Kd-backbones. But once you’ve had all of those drugs, if you’re triple-class refractory or penta-drug refractory, bortezomib, carfilzomib, Len, Pom [pomalidomide] and CD38, then what do you do? You have a few choices; 96-hour infusion regimen, salvage transplant, celly, belantamab, melflufen of course came off the market, Iberdomide, with some encouraging data. But what you see here is that the response rate is about 20% to 30%, PFS, 3 to 4 months. And that’s what we were expecting historically.

Transcript edited for clarity.