Recent Clinical Data

Dr. Usmani:

Amrita, you actually presented data at recently concluded ASCO meeting as well. So, the commentary there is for CAT T-cells, you have to go to a [TCD 00:00:23] center. Their concerns about capacity at those centers, manufacturing slots, and such, whereas biospecifics can be good off the shelf option. So what are your thoughts on that? What is your take on the data? You presented these data so I’d love to give comments from you.

Dr. Krishnan:

Thank you, Saad. So, certainly I think the two that stand out to me the most from ASCO were Teclistamab, and you’re very familiar with that. Trials we’re both co-PIs on that study. And several things, certainly response rate in a heavily pretreated patient population and meeting at five prior lines of therapy to get response rates about 65% is pretty outstanding. As you said, within easily available off the shelf product.

Second thing, I think that stands out to me is the low rate of high grade CRS with really… Most patients getting grade one and grade two, because of the way we give these five specifics with the step up dosing patterns. So it suggests you may be able to do this in older patients, more frail patients as well.

And as you alluded to, patients who have aggressive quick relapse, you may not have time to them manufacture CAR T-cells versus having something ready.

And then there was another one was also presented at ASCO, another BCMA directed by specific that was in patients with a median of eight prior regimens, which is pretty amazing. I think what stood out to me about alratinab was about 20% of those patients had had other BCMA targeting therapies, including CAR T and antibody drug conjugates, and they were still able to see responses. I think that really is something new that we’re now also gives us great hope.

Dr. Usmani:

Thanks, Amrita. I echo your comments here. And then the one thing that I also want to emphasize is the responses we’re seeing in patients with high risk features, including high risk cytogenetics, extramedullary myeloma. It appears that the responses are comparable to the overall population as well. I think that with the small molecules and pathway-directed therapy is… Or plasma cell pathway-directed therapies in the past, we’ve always had this concern about activity and standard versus high risk. But We’re seeing comparable activity with CAR T’s and biospecifics for these more high risk patients.

What were the key takeaways from ASCO and EHA? There were combination datas with selinexor, iberdomide. Since you lead the Venetoclax combination trials, I’d love to get your comments on all three and maybe an opinion from Amrita after that.

Dr. Kumar:

Certainly, I think [widely 00:03:31] therapist have kind of taken the spotlight. There are clearly other mechanism-based approaches that would be of great value. The positioning selinexor is already approved. We know that that’s in combination with dexamethasone response rate, about 30%.

But I think given the way we use drugs in myeloma, I think the combination data is probably what is most relevant. And across the past couple of years, we have seen, including the recent data, that selinexor can be combined with both monoclonal antibodies, the next generation, particularly [confrencimab 00:04:07]. And then, and also with the image like [pormidobide 00:04:09] , and all of those three combinations appear to be quite effective. Obviously we don’t have randomized data in those settings, but if you were to use, selinexor which would be mostly in the setting of patients who have become refractory to those earlier classes, then we can certainly consider using one of these combinations based on the patient’s tolerability and how long ago they had seen one or more of these drug classes.

Now, with respect to the Venetoclax, I think the data is very strong with just dexamethasone combination or a single agent in the [glad 00:04:44] transfiguration of 14 patients. And we are seeing data with both confrencimab and [tratimobab 00:04:50]. Both of them appear to be quite effective. And again, this is not approved for use in myeloma, but they have been off-label use in patients with translocation level 14, and again, mostly combinations, but even just the dexamethasone tablets seems to be quite effective in that setting.

And then we have clearly the next generation [immidomoderate 00:05:19] drugs that imaged the iberdomide data that was presented again in the multiple different combinations is quite interesting. Obviously the combination with daratumumab and with [partisonate 00:05:34] both of them appear to be quite interesting.

I think what was striking was that the response rate was almost 50% of all these three combinations that were studied, but the hematological toxicity, particularly the neutropenia that was seen with intractable Webb combination was quite striking. And one wonders if that could be an impediment in the future to take this combination forward.

It may be a different story in the newly diagnosed setting once it gets there. But I think the key takeaway point with iberdomide is that it was active in patients who are refractory to [pomalidomide 00:06:10]. It’s a play opens up an additional option for these patients.

Dr. Usmani:

I think that’s a very important point, Shaji.