Episode 58: The ENDURANCE (E1A11) Myeloma Trial in NEJM

Hot off the press, the ENDURANCE trial was JUST published in NEJM. This trial explored whether patients with newly diagnosed myeloma benefit from long-term maintenance lenalidomide versus 2-years only. Dr. Vincent Rajkumar, senior author on the paper, shares the findings and context. Please subscribe, share, and join the conversation. 

Transcript

SPEAKER_00 0:00

Overall survival was identical between the limited duration versus the continuous therapy. Our conclusion is that limited duration maintenance provides the same overall survival, similar PFS, with less toxicity in the treatment of newly diagnosed myeloma. Myeloma is a disease where we have shown time and again more may not be always better.

SPEAKER_01 0:20

It answers a very important clinically relevant question. Proved once and for all that this is not needed. It's reassurance for patients and for digital physicians. So sit back and enjoy the show. Vincent Rajkumar, you're back on the show Healthcare on Filtered Express. First of all, congratulations on yet another excellent paper in the New England Journal of Medicine. I appreciate you coming on and sharing with us the what this what the results of this paper are. And giving the Healthcare on Filtered Express kind of an exclusive, you know, we're we're airing this right away. So let us know about tell us about this paper.

SPEAKER_00 1:15

Thank you so much, Shadi, for having me. Uh this is a randomized control trial led by E.Cog Akron. Uh it randomized over 500 patients with standard risk myeloma not undergoing stem cell transplant to the standard of care, which is lenodamide maintenance until progression, versus a limited duration, two years fixed duration maintenance. Um my colleague at Mayoclinic, Dr. Shahji Kumar, was the PI of this, is the PI of this trial. Uh the primary endpoint was overall survival. So what we found was that um overall survival was identical between the limited duration versus the continuous therapy. PFS was also not significantly different. Grade 3, 4 adverse events were higher as expected with the continuous arm, and so was there there was also a slightly higher risk of second primary malignancies in the indefinite arm. So our conclusion is that limited duration maintenance um provides the same overall survival, similar PFS with less toxicity in the treatment of newly diagnosed myeloma. And uh I think this is surprising.

SPEAKER_01 2:25

It's surprising, no, because we always thought if you continue the therapy indefinitely, you get at least better PFS.

SPEAKER_00 2:33

Well, you know, myeloma is a disease where we have shown time and again more may not be always better. We did that with dexamethasone years ago, and now we are showing that with lenaldomide, and in between there were many other things that came, including bothesimib once a week and lower doses of uh other drugs.

SPEAKER_01 2:49

You know, I love the idea of this trial because I do think it answers a very important, clinically relevant question, right? I mean, this is not a novel therapy, it's a therapy that's been used forever. I mean, this is I I put this in the carrier of a very pragmatic trial. This is a the these are patients seen in the community, many of them were receiving linodomide forever as maintenance, and now you proved once and for all that this is not needed. It's reassurance for patients and for the treating physicians.

SPEAKER_00 3:20

Yes, and I think it goes back to the fundamental idea that for drug approval, many, many drugs are usually approved with a study design of indefinite treatment until progression for the experimental drug versus um observation or a standard of care. Um, once the drug is approved, these types of trials are needed to determine whether you need indefinite duration or can shorter durations, whether it's response adapted or MRD-directed or uh fixed duration are sufficient.

SPEAKER_01 3:53

And the dexamethasone example that you gave is an excellent example of something that's really transformed how we do uh myeloma. You know, there are cost implications to this as well, right? If you are using lanilidamide forever for these patients, the um the amount of dollars being spent on health for in the healthcare system are just astronomical, looking at how much the cost of lanilidamide. Uh, do you want to comment on that a little bit?

SPEAKER_00 4:19

Well, uh consistently lanilidamide is in the top three to five drugs that Medicare spends money on. Um and and that's for a cancer which is only 1% of all cancers. So I expect that there will be cost savings.

SPEAKER_01 4:34

Yeah, no question. Well, I mean, congratulations on the paper. Anything else you would like us to share with viewers and listeners? I'm very excited about this, and um, you know, this will uh we bring this right away as it as the embargo is being lifted.

SPEAKER_00 4:49

I heard that there might be an editorial, so if there is one, I hope they say nice things about our paper. It all depends who writes the editorial.

SPEAKER_01 4:57

So Dr. Vincent Rajkuma, what what what's the mnemonic of this uh of the actual um uh uh trial? Did it have an actual uh name?

SPEAKER_00 5:07

I forgot to say that. It's called the Endurance Trial.

SPEAKER_01 5:10

The Endurance Trial published in the New Jersey Messenger. Congratulations to you and all of the co authors. And thank you for coming on Healthcare Unfiltered Express. Thank you. Thank you for listening to this edition of the Healthcare Unfiltered Express. Until next time, take care.