Updates in Use of Proteasome Inhibitors for Relapsed/Refractory Multiple Myeloma - Episode 2

Multiple Myeloma: Real-World Data With Proteasome Inhibitors


Shared insight on how real-world experience and data with proteasome inhibitors in multiple myeloma compare to what was seen in clinical trials.


Paul G. Richardson, MD: In terms of making sense of the data around ixazomib use, I wanted to emphasize how we found that when we translate from phase 3 information to clinical practice, how certain drugs have performed. In that context, when we look at the various classes of drugs we’ve used, when we look at proteasome inhibitors, it’s very interesting to see that in terms of oral proteasome inhibitors, there’s been a high degree of reproducibility from what we’ve seen in carefully controlled phase 3 trials into real-world practice. I just wondered, Cristina, what your impressions are of this, because this has become an important aspect of what we do.

Cristina Gasparetto, MD: I’ve been thinking a lot about these slides and the message. I think about the evolution of myeloma over the last 20 years and the introduction of many drugs. We’re becoming more sophisticated in understanding the biology of the disease and following patients, but there is a dichotomy here with how we treat a patient aggressively in academia, versus what’s going on in the real world. Are patients able to sustain therapy for a prolonged period? Are they able to stand the toxicity of some of the strategies that we’re proposing? This is opening a huge conversation. We’re impacting the survival of patients with myeloma, but not necessarily all patients. We still have a fair amount of patients with myeloma treated where we are improving the outcome, but not necessarily the survival of all patients. I want to hear your thoughts about this work since you’re actually part of it.

Paul G. Richardson, MD: Cristina, you’re touching on an absolutely critical point. That critical point is that, in the context of clinical trials, there are highly selected patients who have outstanding performance status and reflect a patient population who do not necessarily prove to be representative of what goes on in real-world practice. In academic centers, where for example, the achievement of maximal high quality response, the holy grail of MRD [minimal residual disease] negative status, which I have many cautions about, particularly in the relapsed/refractory setting. In the upfront setting, there are some different considerations, but in relapsed/refractory disease, a disease control that’s associated with high quality of life and minimal toxicity by virtue of effective therapy, is a win. That doesn’t necessarily involve driving for maximal response.

What you see here in this particular table, for example, illustrates a bit of that by showing you that, as you can see with an oral proteasome inhibitor combined with an immunomodulatory agent, you can see progression-free survival [PFS] information or time to next therapy, which is a very important parameter of clinical benefit, actually, and somewhat underappreciated. You can see that in the clinical trials, we were looking at 18 to 21 months, and then when you look at real-world reports, there’s a very high degree of reproducibility. Conversely, some of the more potent drugs that we use, and just by way of example let’s pick carfilzomib, an amazing drug as you so nicely framed. In clinical trials, we’re looking at 15 to 22 months of clinical benefit, be it PFS or time to next therapy, which is outstanding. If you look then at real-world reports, those numbers change. That reflects this whole issue of tolerability, and this whole issue of the convenience of oral bioavailability, which obviously ixazomib exemplifies. That theme is brought out in this table because lenalidomide as an oral therapy performs very well in the same context, fully recognizing that, nonetheless, you need the punch of certain proteasome inhibitors in certain places. Carfilzomib nicely does just that.

Transcript edited for clarity.