Optimal Treatment Sequencing: Trial Results

Dr. Usmani:

When speaking about anti-CD38 based combination triplets, we have several options in the early relapse, one to three prior lines of treatment. And, I want to get Amrita’s take on the data, especially in the context of the Candor and IKEMA studies for the Len-refractory patients because vast majority of our patients are on Len maintenance and they’ll be considered Len-refractory by the IMWG definition. So, what are your thoughts around some of the updates that were presented about these options in the early relapse setting?

Dr. Krishnan:

So, I think at that early Len-refractory setting, now you have sort of… Certainly, most of us will immediately use that anti-CD38 backbone. Usually, your question really is, is it going to be which anti-CD38 first, and then the partner is also important. So looking at, is it going to be pomalidomide or is it going to be carfilzomib-based? Again, as you said on the ICAP Korea data, the IKEMA data, PALA data. And, I bet you’ve sort of swayed me a little bit aside from some of our recent conversations, I tended to be more wedded to the anti-CD38 pomalidomide regimen as my next go-to and part based on patient preference to some degree of convenience. But, really, if you look at the IKEMA data in terms of the hazard ratios, it’s pretty striking and same with the Candor data.

And so, certainly patients in aggressive relapse, I have now been swayed to use that as my sort of next line of therapy. I admit still caution, at least when you look at Candor in terms of those patients over age 65 and higher incidents of infection, sepsis, but again, you talked me into that it’s manageable. And, so I’ve again been now a little less… and more willing to explore that even in older patients.

Dr. Usmani:

Yeah. I think the only caveat that I’d say is if someone… I agree with you, I think both pom and carfilzomib based anti-CD38 combinations would be reasonable choices. And, we can always individualize based on patient’s comorbidities. Someone who already has cardiac issues, maybe pom would be a better partner in that scenario. Or, if someone is having a symptomatic relapse, maybe a class switch carfilzomib may be a better, better option for them, especially if they have high risk features too. So, one can… It’s just that we have more options in that space. So, but I have a personal bias towards the PI-based combination in that setting with an anti-CD38, because the PFS we see in the Len-refractive patients is, it’s quite impressive compared to the other options.