What’s New for Newly Diagnosed Multiple Myeloma | Rahul Banerjee, MD, FACP

My name is Rahul Banerjee.

I'm an assistant professor of medicine and a myeloma specialist at the Fred Hutchinson Cancer Center in Seattle, Washington.

And now I've been asked to talk about what's new and newly diagnosed multiple myeloma in 2025 and in particular at the at this particular American society hematology, ASH meeting in Orlando, Florida.

In short, nothing has changed immediately in this particular setting.

I think the standard that really has been established over the last year at sequential meetings and publications is the idea that the default for all patients with multiple myeloma should be consideration of a quad, a quadruplet, which means a CD38 binding antibody like daratumuma, isatuximab, a proteasome inhibitor like bortezomib, carfilzomib, an IMiD drug, typically lenalidomide and dexamethasone.

Five years ago we would have said, oh, you know, only the healthiest patients get a quadruplet or only the high risk patients get a quadruplet. And I would say everybody, even the patients over 80.

There was data presented earlier this year, published earlier this year, I should say, from the Norwegian group, the rest trial by Frida Askeland and Fredrik Schjesvold showing that even in patients over 80 whom you don't the concurrent quadruplets.

Ironically, if you get rid of the dexamethasone—and I love getting rid of dexamethasone—if you get rid of dexamethasone after two cycles and keep the other three drugs, many of those patients can tolerate a quaduplet quite well.

So again, that is the backdrop here. Pick a quad. Any quad for the vast majority of newly diagnosed patients.

The unanswered question is which quad. Dara-VRd, a daratumumab and bortezomib. Dara-KRd, the daratumumab and carfilzomib. Isa-VRd, isatuximab and bortezomib. Isa-KRd, isatuximab and carfilzomib. How do you choose? Let me know if you find out you're not just by now because we don't know at the current time.

What I will say is dara-VRd tends to be the default again. Daratumumab, bortezomib, lenalidomide and dexamethasone for our patients in the US, newly diagnosed myeloma.

Based on studies like the Griffin study and Perseus study, and now the Safia study, Isa-VRd is entirely reasonable for patients based on the Emerus and benefit studies. Many of these studies are out there.

What was interesting here at the 2025 ASh meeting is there has been a perennial debate between bortezomib and carfilzomib in multiple myeloma newly diagnosed myeloma.

Up until this meeting, in the relapse setting, carfilzomib—the brand name is Kyprolis—has outperformed bortezomib—brand name Velcade—and the Endurance trial.

In frontline myeloma, there was a big endurance trial, a co-operative group trial, meaning one by the doctor, not by the pharmaceutical companies, looking at KRd versus VRd. And there were really no difference between them in terms of outcomes.

However, most of the patients did not go on to transplant, and the carfilzomib in the use with 36mg per week twice per week, which I'll hazard a bet that none of you listening to this ever receive. Most patients nowadays receive 56mg once a week, or 70mg once a week, once a week.

Here there was a Polish led study, called a Cobra trial of KRd versus VRd and primarily transplant eligible patients. At face value, KRd blew VRd out of the water. Truly, like MRD negative rates were better. Efficacy was better. Safety was the same devil in the details that particular study.

Patients who are on carfilzomib on that arm stain on carfilzomib for about 1 to 2 years, basically going from once a week to once every other week. The bortezomib arm, the VRd arm only was on VRd for about six months, so it wasn't a fair comparison of K versus V. Bortezomib versus carfilzomib.

So basically, all the arguments that we tend to have in the myeloma field will continue both before and after the Corbra trial.

And again, I'll come back to what I said earlier. Pick a quad any quad.

So if you're an organizer with multiple myeloma, talk to your doctor about whether quad is right for you. And the vast majority of cases, it would be practically all tell patients.

And I tell other doctors this just because you start with a quad, does it mean you are legally required to maintain the quad at full intensity? Most of my patients drop them. Dexamethasone lenalidomide dose comes down due to side effects, etc., etc.

So starting with a quad isn't something that you have to stay on a quad for it to work. Most patients in the real world setting, their regimen they start looks very different from what they end with at the end of induction, but that's okay.

Starting with a quadruple, it gets you your best foot forward to knock the myeloma into remission to earliest and feel better sooner. Whether that is what's carfilzomib or bortezomib remains an unanswered question.

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