Dose Modification and Premedications Aid in Tolerability of NDMM Therapy

Stephanie L. Elkins, MD

Division Director, School of Medicine

The University of Mississippi Medical Center

Jackson, MS

DISCUSSION QUESTIONS

• How do you manage adverse events (AE) for patients receiving induction therapy? ​
• Does your choice of induction therapy impact your choice of consolidation and maintenance therapy in patients with transplant-eligible multiple myeloma?

STEPHANIE L. ELKINS, MD: What do you do in induction therapy for AE management? Do you do anything different for triplet vs quadruplet therapy? What do you do in general, to preemptively manage your expected AE?

ETHAN TOLBERT, MD: We had a discussion recently, where everyone was in agreement that we're all doing bortezomib [Velcade] weekly to try to prevent neuropathy, as opposed to twice a week. That's one example.

ELKINS: Absolutely. Do you [give bortezomib] subcutaneously or intravenously?

TOLBERT: Subcutaneously. I will typically lower the dose of lenalidomide. I don't give anybody 25 mg….

ELKINS: What do you use?

TOLBERT: [I use] anywhere from 15 mg to 20 mg.

ELKINS: Do you intensify your dose based on [the patient’s] tolerance?

TOLBERT: No, I usually keep them with the same dose.

ELKINS: Does anybody else do that with their regimen?

LORENA A. DE IDIAQUEZ BAKULA, MD: I use the full dose, except for patients who have renal failure or who are over the age of 70. Otherwise, we just push through and sometimes you have to support them during the first cycle, but in general it's tolerated very well.

HARISH MADALA, MD: I usually start high and if they're tolerating well, continue it, and if they're not, then titrate down. I'm trying to maximize the dose they can tolerate. In addition to that, I'm starting to give more IVIG [intravenous immunoglobulin] of late to offset any infectious complications. That's the only additional change [to treatment that] I have made.

ELKINS: Do you do that just for the patients who have a low IgG [immunoglobulin G] level who are getting infections or you do it for everybody?

MADALA: I used to be in a group where I used less IVIG in the past, but of late, I'm using it in most of my patients irrespective of their immunoglobulin levels.

PETER JIANG, MD: Is there a theoretical risk of IVIG working against the daratumumab [Darzalex]?

ELKINS: No, I don't know of any. It's a good question. I don't know that I've ever seen any data that say that one way or the other.

JIANG: We use IVIG but quite often the insurance company declines because of the level of IgG. When we talk to [Winship Cancer Institute of] Emory University they say they don't care about the IgG level because these patients have less functional IG anyway, so they can give IVIG for most people, because they [are able to get it] approved from the insurance company. That's a challenge for the community practice, [however].

ELKINS: I don't routinely give IVIG. I supplement my patients who get infections, but I have seen some information lately talking about supplementing outside of the group that gets infected. I just haven't done it as of yet. I do start with 25 mg of lenalidomide and will titrate down if they have toxicity, but most of the time I can get 25 mg in. The only other AE management I do is that I put all my patients on acyclovir. I'm sure you probably do as well, just because of that HSV [herpes simplex virus] reactivation, but I don't do anything differently. Of course, everybody premedicates for daratumumab as [indicated in the package label].¹ That's the difference between triplet and quadruplet therapy to me, that you have to add that extra premedication in.

JIANG: The dosage of dexamethasone [is an issue], especially with patients with poorly controlled diabetes. Sometimes it's hard to control. What lower dosing do you give a patient?

ELKINS: I try to do at least 20 mg weekly. A lot of my patients don't like 40 mg. But I like to do 20 mg if I can. Every now and then I've got a patient whom I'll take all the way down to 8 mg. I figure a little bit is better than none. If they absolutely cannot tolerate even 20 mg, I usually just drop a 4 mg pill until I get to a dose that I think they can tolerate. I also sometimes split it and do 10 mg [twice weekly], or 20 mg [twice weekly], trying to not have that big dose all at once. Steroids are hard. We think that’s the easiest part of what we do, but they’re very difficult [to use in this patient population].

DE IDIAQUEZ BAKULA: I agree, I do the same. I only treat with a weekly dose. I never give more than 20 mg to an older patient. I’m very quick at dropping the dose in diabetic patients, especially if I cannot get their diabetes under control. Sometimes they don’t even tolerate metformin very well when they [receive] lenalidomide [Revlimid], so they have a lot of diarrhea. In some patients who already have significant neuropathy, I’m very careful with for how long I want them to have uncontrolled blood sugar, because otherwise I leave them with a problem and it’s going to stay around for a long time. There are patients in whom I simply stop the steroid, especially with triplet or quadruplet regimens. I find that, for the most part, we are achieving what we are aiming to achieve. Even for nontransplant candidates, I may do the same because I'm always keeping in mind the long-term picture.

ELKINS: I think you have to. The long-term picture for patients with multiple myeloma is a lot longer than it used to be.

CHANDAR BHIMANI, MD: We are not doing the consolidation at cycle 5 or 6. I don't know whether it's a European [approach]. Usually when we do the induction followed by transplant [there is] no consolidation and [we go] directly to the maintenance.

ELKINS: I have traditionally not done consolidation either. But the more recent studies all support an additional cycle or 2 after transplant. I'm beginning to do 2 cycles. I generally give whatever they got for induction for their consolidation and look at 2 cycles posttransplant and then transition to maintenance.

_References:

_{1. Darzalex. Prescribing information. Janssen Biotech, Inc; 2022. Accessed May 23, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761036s041lbl.pdf}