Multiple Myeloma: Planning a Continuum of Care in 2020 - Episode 12

BELLINI Trial; Venetoclax-Vd in Multiple Myeloma

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Keith Stewart, MBChB: Let’s discuss venetoclax, which has taken us by storm in the last year or 2. Tom, you were an early adopter of venetoclax. Tell us about your experience. What do you think of the BELLINI clinical trial? Maybe you could describe what that is.

Thomas G. Martin, MD: Venetoclax is an inhibitor of BCL2. We started using it in relapsed/refractory before selinexor was approved. We could get it in some patients by compassionate use. We had about a 20% response rate with venetoclax plus dexamethasone with people who were triple-class refractory. But what was found by several investigators is that those patients who have the 11;14 translocation likely have overexpression of the BCL2 pathway. But those people are exquisitely sensitive to this BCL2 inhibitor, and they had a really nice response. A phase 2 was done, randomized bortezomib–BCL2 inhibitor–venetoclax and dexamethasone vs bortezomib and dexamethasone, showing a benefit in people with 1 to 3 prior lines of therapy, all comers. That instigated the BELLINI trial, which was a phase 3 randomized trial, in patients with 1 to 3 prior lines of therapy. And patients are randomized to the triplet vs the doublet of bortezomib and dexamethasone. What we found is that the triplet actually was more toxic. In fact, there was higher mortality. It was updated at ASCO [American Society of Clinical Oncology Annual Meeting] this year by Dr Shaji Kumar showing that that toxicity still persists, that there were more GI [gastrointestinal] toxicities, more infections, and there was some cardiac toxicity in the triplet vs the doublet. In that study was a subset of patients who had the 11;14 translocations. Those patients had exquisite responses. The overall response rate was well over 90%. After 2 or 3 years, these patients remained in remission PFS [progression-free survival]. That curve is an impressive curve in the 11;14s. It’s going to be a great drug for the patients who have the translocation at 11;14. But for everybody else right now, they’re probably not going to move forward in that direction.

Keith Stewart, MBChB: Thank you, Tom. Natalie, are you using it in clinical practice yet?

Natalie S. Callander, MD: We would have, we have had a lot of trouble getting payers to approve it, even with the presence of 11;14. That’s been the biggest hurdle. We’ve had a couple of patients who were treated through the VA [Veterans Affairs Medical Center], where they’ve had nice responses again. This is going to be a drug for the 11;14. Unfortunately, because of the BELLINI trial results, it’s put a damper on a lot of the research that we’d all like to see done. Hopefully, there’s going to be recognition that there are patients who benefit from this. But it’s put the brakes on a lot of things.

Keith Stewart, MBChB: Peter, last word to you before we move on to something different?

Peter Voorhees, MD: I agree that in 11;14-translocated, in BCL2-high patients, it’s a very active agent. We’ll see it eventually get approval there. I do want to give a quick shout-out to the daratumumab-venetoclax-dexamethasone data that presented at ASH [American Society of Hematology Congress] in December. The overall response rate was over 90%, and every single patient was either a VGPR [very good partial remission] or CR [complete response]. Granted, they were small numbers.

Keith Stewart, MBChB: Yes, I must say, I’ve used quite a lot of venetoclax, and these are very impressive results in the 11;14 population, as you’ve all said. Unlike Natalie, we seem to be able to get it quite easily, at least until a couple of months ago. I don’t know if that’s changed. For the folks watching, if you have an 11;14 translocated patient—first, test for it, because you won’t know unless you do the test. Second, a lot of the commercial labs aren’t running 11;14 testing. You have to be careful that they’re actually measuring it. And if you do find somebody with that, it’s a drug to consider as a single agent or in combination.

Transcript edited for clarity.