Reactions to Updated Isatuximab Data in Second-Line Multiple Myeloma

Suzanne Lentzsch, MD, PhD

Professor of Clinical Medicine

Director of the Multiple Myeloma and Amyloidosis Program

The College of Physicians and Surgeons of Columbia University

New York Presbyterian Hospital/Columbia University Medical Center

DISCUSSION QUESTION

• What are your thoughts on the updated progression-free survival (PFS) data with a median of 44 months follow-up in the IKEMA clinical trial (NCT03275285)? ​

ALEXANDER BARSOUK, MD: I think these are important data, with the consideration that nowadays almost everyone receives a CD38 therapy upfront. But there were no daratumumab [Darzalex]-refractory patients—so the question is, if somebody progressed on a frontline regimen including daratumumab, would you switch to isatuximab [Sarclisa]? But the point is well taken. For patients with a 1q21 [chromosome] gain, this seems to be very favorable.¹

YACOUB FAROUN, MD: The data is very appealing, with a 41-month median PFS across the board. But it was strange in this study that 41% of these patients have abnormality of chromosome 1.

SUZANNE LENTZSCH, MD, PHD: Yes, it was [41.9% in the isatuximab arm], almost half of the high-risk patients.It is not half of the patients; you have to think about the data. Twenty-five percent were high risk and half of them had a gain of 1q21.

GABOR VARADI, MD: Are there any data that daratumumab [followed by] isatuximab works?

LENTZSCH: I think it’s very difficult to decide whether to move directly from daratumumab to isatuximab. Does anyone has experience with this, if you use daratumumab, you have no response or relapse, then you switch to isatuximab?

VARADI: I don’t think there are any data for that.

FAROUN: There would be no data. But, again, these are 2 different agents, with 2 different targets. This is my limited experience, but patients who progress on daratumumab responded very well to isatuximab.

LENTZSCH: The target is the same. If patients are truly relapsing on the daratumumab and downregulate the target with CD38, I think it will be hard to achieve a response with isatuximab without a break. If the patient is on daratumumab, relapses, but maybe has a break without a CD38 monoclonal antibody for 6 months or a year, so that the antigen recovers and is expressed on the cell, I think then it would make sense to go with isatuximab. There are some smaller studies, investigator initiated, that show there might be a response but it was not striking. So I would probably favor a class switch, but I think what is interesting is the high number of patients responding with high-risk cytogenetics.

FAROUN: When you use triplet therapy, you change, for example, from an immunomodulatory drug [IMiD] to a proteasome inhibitor [PI], like carfilzomib [Kyprolis]. So is it carfilzomib that is driving the response rate or is it the isatuximab?

LENTZSCH: What would be be best would be a head-to-head comparison of isatuximab, carfilzomib, and dexamethasone versus daratumumab, pomalidomide [Pomalyst], and dexamethasone.

DISCUSSION QUESTIONS

• What is your reaction to the updated data from IKEMA besides PFS? How do you view the efficacy and safety of this regimen? ​
• How do these data compare to those of other standard triplet regimens used in this setting? ​
• Do you agree with this treatment approach?​

LENTZSCH: Do you have any other reaction to the IKEMA data? There was a pretty impressive PFS. How do you view the efficacy and the safety? How do you compare the data with isatuximab/carfilzomib/dexamethasone to the standard triplet regimens?

MEHER BURKI, MD: I think the data are pretty convincing. I personally have not used this regimen, but the data show doubling of PFS so that’s impressive.

ASHISH KHOT, MD: I think if a subcutaneous formulation comes out, it would help us as well. It’s so easy to give subcutaneous daratumumab with pomalidomide. That way the patients wouldn’t have to stay, and don’t have to come to the infusion center. It’s much easier.

LENTZSCH: I agree. That is a game changer, that patients need just 5 minutes infusion chair time, then 75 minutes [monitoring after an injection].

BURKI: I also feel if we get any data for giving it after progression on daratumumab, that would be another game changer, if anybody is ever going to do a trial to prove that.

LENTZSCH: If there would be a subcutaneous formulation, would you easily switch, especially if the price is good?

BARSOUK: Oh yes, absolutely. I think for daratumumab, historically, that was what made it a game changer because we went from 8, 10, sometimes 12 hour infusions…to 5 minutes and there were no problems. So that was a significant game changer. And same for isatuximab, if it comes with a comparable subcutaneous formulation, that would be a very good move, and if the price is right too.

LENTZSCH: That would also be fantastic for our patients.

FAROUN: Let’s say in the near future we’re going to have subcutaneous isatuximab formulation available for commercial use. Would we continue subcutaneous isatuximab with intravenous carfilzomib or do you switch to a different oral agent such as an IMiD or PI, like ixazomib [Ninlaro]?

LENTZSCH: That is a good question. In the end, that’s usually what I do. I start to discuss with the patient the regimen that I think is the best for the patient. For instance, in high-risk patients, I like to give carfilzomib rather than bortezomib [Velcade], and then we go down the road. Then we say, what is the background? Can somebody drive you? Are you living in Punxsutawney, Pennsylvania, and you can’t [regularly] come to Pittsburgh? Then I try to address the doable things. So a lot of things go into the treatment decision, but usually I start to discuss with the patient what I think would be best.

Reference

1. Moreau P, Dimopoulos MAC, Mikhael J et al. Updated progression-free survival and depth of response in IKEMA, a randomized phase 3 trial of isatuximab, carfilzomib and dexamethasone (Isa-Kd) vs Kd in relapsed multiple myeloma. Abstract presented at: 2022 European Society of Medical Oncology Virtual Plenary, May 19-20, 2022; Virtual. Abstract VP5-2022.