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
Noopur S. Raje, MD: Relapse is a very common problem in myeloma. The majority of multiple myeloma patients, despite everything we have, will relapse. I think what’s happened over time is the timeframe has changed completely for both the transplant-eligible as well as transplant-ineligible patients. On an average, your first remission is anywhere between 4 and 5 years now. And that would be the first time that a patient will relapse with their disease. And then what we are seeing now is patients are relapsing multiply because even with your first relapse and your second relapse, there are pretty effective treatments available to our patients. And what we typically see in our practice now is patients having had 7 lines of treatment, 8 lines of treatment, and that’s good news.
A few years back, we did not have that many lines of treatment. We do now, and that’s part of the reason why our patients are living that much longer. We’ve certainly made a big dent in how long patients live, and they’re living a whole lot better and in the very refractory state. Right now, it’s usually after 3 or 4 lines of treatment, and on average, anywhere beyond 5 years of their treatment for their myeloma is where you find the truly refractory multiple myeloma patients.
Rafael Fonseca, MD: In addition to some of the clinical trials and the immunotherapies that are being tested, there are other option is for patients who have advanced disease. One of the most looked after set of clinical trials are those that involve pomalidomide combinations. So we have pomalidomide, of course, with its track record in combination with dexamethasone. But I think more and more we’re using it in combinations with other agents. We have the OPTIMISMM clinical trial where pomalidomide was combined with bortezomib with a very high rate of response. It’s a regimen we’ve used quite extensively in the clinic. In fact, just yesterday I saw a patient in the clinic who we used this regimen in 4 years ago. He’s in a CR [complete response]. He’s doing great. This is a person who had a number of other medical problems, with COPD [chronic obstructive pulmonary disease], and was sent to hospice. This patient came out of hospice. Two years later he’s doing well, with good disease control without therapy.
Pomalidomide can also be combined with elotuzumab. We saw a recent clinical trial that was published in the New England Journal of Medicine where they show a high level of activity. They talked of a response rate of close to 60%. This is also very exciting. Elotuzumab is a very well tolerated medication and is potentially another regimen we’re going to be using in this patient population. Pomalidomide has been combined, also, in other settings, such as in a small study with cyclophosphamide. This is an older regimen. We have combinations that include panobinostat. We haven’t used a lot of that because of some of the toxicity, but there’s some clinical trial data that show that it works in a different schedule and with some other combinations including with carfilzomib, so I think that’s another option for patients.
But our first stance, when we see someone who has advanced refractory multiple myeloma would be to do a very careful review of all the drugs they have received previously and then think about combinations we may be missing from those prior lines of therapy.
Noopur S. Raje, MD: Approval of drugs for multiple myeloma is incredibly important, because it opens up access to patients and it opens up availability of those drugs to patients. The most recent approval of pomalidomide with elotuzumab and dexamethasone is obviously a good thing for patients, where it can be used in combination. Having said that, although it’s defined as for refractory patients, as I’ve mentioned earlier on, it does not include patients who’ve seen daratumumab. In the real world, the data may not be exactly based on label, and that’s something we always have to think about in myeloma.
And I think this was true even when daratumumab got approved with the CASTOR and POLLUX studies. There’s a reason why a lot of these approvals happen in Europe and not in the United States, necessarily. That’s because of access to drugs and what is available in those situations. And so, that patient population is more reflective of that geography. I’m not saying that the drug combination cannot be used. It absolutely can be. But you have to temper the results of what you’re going to get if your patient has been exposed to a whole bunch of other drugs. And that’s why getting an approval is a good thing, but really putting that data in the context of your patient and what your patient has had is going to be able to provide you with a more realistic expectation on what the data are going to look like in that particular patient.