Medical Roundtable: New Multiple Myeloma Treatments
Even though these patients didn't stay on therapy for very long, their magnitude of benefit was much longer than for the other subsets of patients in Panorama-1. For the double refractory, or the double exposed subset of patients, the addition of panobinostat seems to be most beneficial. In our own experience, we have partnered panobinostat, not just with bortezomib, but actually with carfilzomib, and have found it to be much better tolerated in combination with carfilzomib.
In fact, Burdeja et al presented some of this data at ASCO this year, and showed that the gastrointestinal toxicity was almost nonexistent in the dose and schedule with which he used panobinostat in combination with carfilzomib.6 I think finding the right partner is really important as well. We have found that for some really high-risk relapses, relapse within a year, aggressive relapses with 17p deletion patients, panobinostat in combination with a PI seems to be a very active combination as well. We're using it right now for those really aggressive high-risk relapses. We may change the partner, but I think we're going to take a little more time to refine who is the best patient population for a histone deacetylase inhibitor in myeloma. I think you're right, it's not clear right now.
Dr. Kalaycio: I agree. I think this will be similar to our learning curve with bortezomib—when first introduced, we gave it intravenously resulting in neurotoxicity, so we learned how to give it subcutaneously to avoid toxicity. I suspect the same will happen with panobinostat and even some of the monoclonals that are soon to be forthcoming.
Dr. Lonial: Yes, I agree.
Dr. Kalaycio: I was impressed by the results of the ELOQUENT trial with elotuzumab in combination. Prior to that, I was unimpressed with elotuzumab as a single agent. I suspect it will get approved in combination, but I don't think that combination is necessarily what people would choose first in the relapse setting. I think it typically would be used with a PI. I'm curious where you think the results of the ELOQUENT trial at ASCO are going to translate into actual practice when it becomes approved?
Dr. Lonial: I think we learned a couple of things from that presentation. We did some of the early phase I work with elotuzumab in combination with an IMiD. The IMiD partnership with a monoclonal antibody is just so strong. I think we've enrolled over 50 patients with IMiDs and antibodies together in combination. The response rate and durability of response is really quite striking.
We have felt left out in myeloma in terms of the fact that we have not had an antibody. In fact, I'm not sure if you've heard my quote about this, but I call it oncologic irony. A disease that makes too much of an antibody doesn’t have an antibody to treat it.
Now we have elotuzumab. Elotuzumab partners very nicely with an IMiD, and not only improves PFS compared to the IMiD dexamethasone combination, but actually seems to prolong the duration of response—even if the depth of response is the same. Just to clarify that, if you take patients that got a partial response (PR) with len/dex, and then look at patients that got a PR with len/dex elotuzumab, the duration of that PR was longer with the antibodies than it was with len/dex alone. The same goes for very good PR or better. This, to me, is the ultimate definition of synergy.
In many trials, it doesn't matter what response level you get to. If you get to that response, whether you were in the control arm or the experimental arm, the PFS is the same. This is one of the first trials that show that the PFS can be dependent on the addition of the immune based treatment or the antibody.
I think that's really a powerful approach. I think it's going to get employed in combination with len/dex. If you think about patients progressing on lenalidomide as a single agent, often times we'll talk about adding in dexamethasone, and adding another agent to that. I think adding len/dex, and adding elotuzumab to that, might be a reasonable approach in the early relapsed myeloma setting as well.
There are lots of new mechanisms of action and drugs to use in the treatment of myeloma. ... I really like the results that it's showing in preliminary analysis.
Dr. Kalaycio: There are lots of new mechanisms of action and drugs to use in the treatment of myeloma. I think time is going to prevent us getting too much into daratumumab, but I really like the results that it's showing in preliminary analysis.
