Transplant-Ineligible Multiple Myeloma

Keith Stewart, MBChB: Noopur, tell us about the MAIA trial. What about using a regimen that doesn’t contain a proteasome inhibitor? What’s your thinking about that?

Nooper Raje, MD: The MAIA trial is the best data that we’ve seen. And it’s 1 of the largest trials in the newly diagnosed space. This is for transplant-ineligible patient population. There are slight differences between this and the ENDURANCE trial. The ENDURANCE trial was supposed to be a transplant-deferred patient population. Having said that, a lot of patients on the ENDURANCE trial ended up getting a transplant. It’s hard to compare this with the MAIA study. The MAIA study was clearly a patient population that all of us see in our practice. These were above the age of 65 years old or not transplant eligible, for whatever reason. And it was close to 1500 patients, so 1 of the largest trials for multiple myeloma in the newly diagnosed space.

The other interesting thing about the MAIA study was it was the first time where they did sort of dose-modify both the dexamethasone and the lenalidomide based on patients’ creatinine clearance, which is something we have to deal with in the real world. They included patients who had slightly softer creatine clearances, which typically has not been done previously in a lot of clinical trials. For all those reasons, the MAIA trial is a practice-changing trial. In the transplant-ineligible patient population, the combination of Rd [lenalidomide, dexamethasone] with daratumumab is a reasonable and a good option for our patients who are transplant ineligible.

Keith Stewart, MBChB: If I’m hearing you right, it’s the VRd [bortezomib, lenalidomide, dexamethasone] for younger patients and dara-Rd [daratumumab, lenalidomide, dexamethasone] for less fit or elderly patients? Is that correct?

Nooper Raje, MD: That’s right. But also, for the younger, high-risk patient population, I would consider KRd [carfilzomib, lenalidomide, dexamethasone].

Keith Stewart, MBChB: Carfilzomib, lenalidomide, dex [dexamethasone] for high-risk, young; bortezomib, lenalidomide, dex [dexamethasone] for most people; and for the frail, daratumumab, lenalidomide, dex dexamethasone. Does anybody disagree with that algorithm?

Peter Voorhees, MD: I wouldn’t necessarily restrict dara-len-dex [daratumumab, lenalidomide, dexamethasone] to frail patients. I think older patients with standard-risk cytogenetic profiles are good candidates for that approach.

Natalie S. Callander, MD: I would agree with that. For the very frail, I still consider a doublet at times, particularly if they can’t get to clinic very often, Rd [lenalidomide, dexamethasone] still has some pretty good responses in that population in particular—as Noopur said about dosing for creatinine clearance.

Keith Stewart, MBChB: Rd being lenalidomide-dexamethasone.

Natalie S. Callander, MD: Right.

Nooper Raje, MD: The only thing for the MAIA patient population is that high-risk patients don’t seem to do that well with the monoclonal antibody and Rd [lenalidomide, dexamethasone]. There’s room for RVd [lenalidomide, bortezomib, dexamethasone] light, so bortezomib is given in a weekly schedule for patients who are older and have high-risk cytogenetics.

Keith Stewart, MBChB: Fair enough. We have to move on for time here. What about our patients with renal failure? How does that change the equation, Peter?

Peter Voorhees, MD: These patients in acute renal failure are oftentimes in the hospital when they’re first diagnosed. You have rapid access to cyclophosphamide-bortezomib-dexamethasone in that situation. You don’t have to worry about renal modifications with that particular regimen. Starting with CyBorD [cyclophosphamide, bortezomib, dexamethasone] in that particular patient population is very appropriate.

But what we tend to do more and more now, since we do have comparisons to, say, CyBorD [cyclophosphamide, bortezomib, dexamethasone] versus VTd [bortezomib, thalidomide, dexamethasone], and now we have KCd [carfilzomib, cyclophosphamide, dexamethasone] versus KRd [carfilzomib, lenalidomide, dexamethasone]. And we do see improved depth of response with the IMiD [immunomodulatory imide drug]–proteasome inhibitor [PI] triplets. What we’re typically doing with cycle 2 and beyond is we’re converting to IMiD-PI-dex [dexamethasone] and just modifying the len [lenalidomide] dose, depending on where their renal function ultimately stabilizes.

Keith Stewart, MBChB: Would you use daratumumab there? Because that’s off the shelf and ready to go, you can give it in renal failure?

Peter Voorhees, MD: In the inpatient setting, it’s a bit more problematic. But on the outpatient setting, that would be a consideration.

Transcript edited for clarity.