Insights From: Kenneth C. Anderson, MD, Dana-Farber Cancer Institute and Harvard Medical School; Rafael Fonseca, MD, Mayo Clinic; Noopur S. Raje, MD, Massachusetts General Hospital Cancer Center
Kenneth C. Anderson, MD: This was the clinical trial in patients with relapsed/refractory [R/R] myeloma. There were 117 patients enrolled, and either received elotuzumab/pomalidomide/dexamethasone, versus pomalidomide/dexamethasone.
And so, these were patients who were already, or whose myeloma was already, refractory to bortezomib and lenalidomide. So they were often refractory to the first generation of the 2 agents. That’s important because this elotuzumab/pomalidomide/dexamethasone, when compared to pomalidomide/dexamethasone alone, really was remarkably better. The progression-free survival with elotuzumab/lenalidomide/pomalidomide/dexamethasone was 10.3 months versus 4.7 months for the pomalidomide/dexamethasone alone. And the complications or adverse events actually indicated that the addition of elotuzumab to the pomalidomide/dexamethasone did not really markedly increase the adverse profile. Importantly, the hazard ratio was 0.54, which means that there was a 46% decrease, or risk, of progressing to myeloma or death by virtue of adding elotuzumab to pomalidomide/dexamethasone.
So this particular clinical trial, in patients who, primarily in North America, would be refractory to lenalidomide and bortezomib treatment, now offers us an FDA-approved regimen for relapsed disease incorporating the novel monoclonal antibody elotuzumab. It offers us a wonderful, new opportunity to treat our patients.
Noopur S. Raje, MD: The ELOQUENT-3 trial was a trial comparing pomalidomide/dexamethasone with pomalidomide/dexamethasone with elotuzumab. Now this combination is very safe. It is very well tolerated. Elotuzumab, as a monoclonal antibody, is an extremely well tolerated drug. The benefit of adding elotuzumab to the backbone of pomalidomide/dexamethasone is actually incredible because it doubles the response rates and doubles the progression-free survival rate, which is incredible. I would not have expected to see that. So it’s a great combining partner, and it really does not impact the toxicity of the pomalidomide/dexamethasone combination.
Really, if you look at the data from ELOQUENT-3, looking at pomalidomide/dexamethasone versus pomalidomide/dexamethasone/elotuzumab, and if you didn’t know which arm was which, you were not going to be able to see a big difference in terms of toxicity. So I think with elotuzumab, most of us would agree there’s no toxicity issue. The issue is, how durable are the responses that you see with the addition of elotuzumab given that elotuzumab, as a single agent, doesn’t have a whole lot of activity in myeloma.
The ELOQUENT-3 trial, again, included all kinds. And in fact, I think the nice thing about the ELOQUENT-3 trial is it’s one of those trials where they had a lot of patients who were Revlimid [lenalidomide] exposed, or were Revlimid-refractory. And again, it begs to that same question that we were discussing earlier on. If you had an IMiD [immunomodulatory drug] before, could you have an IMiD again? And the answer to that, based on the ELOQUENT-3 trial as well as the OPTIMISMM trial, which is pomalidomide/dexamethasone with bortezomib, is that you can use a pomalidomide-based or pomalidomide-containing regimen, even if you’re refractory to lenalidomide.
The addition of elotuzumab was beneficial in all subgroups, including in high-risk genetics as well as all ages. And that largely speaks to all ages, specifically, because it does not compound toxicity, which is really an important part of adding elotuzumab to the pomalidomide/dexamethasone backbone.
We tend to use pomalidomide a lot earlier. Most of my patients will see pomalidomide at their first or second relapse. We are not using it for really refractory patients, and that’s largely because in the upfront setting we’re using combinations. The majority of them are on a lenalidomide-containing regimen, so their next regimen is pomalidomide. What I use for the partner with pomalidomide depends on the kind of relapse and the kind of toxicity profile from their previous treatment. If they have neuropathy, I’m not going to use bortezomib. I would use elotuzumab in that setting. If they don’t want to come in for once-a-week treatment with carfilzomib, again I would pick elotuzumab in that setting. But I tend to use a pomalidomide-based regimen for a first or second relapse. And depending on the kind of relapse, I would be really comfortable using elotuzumab in that combination.