Supportive Care for Maintenance in Transplant-Ineligible Multiple Myeloma

Amandeep Godara, MBBS (Moderator)

Assistant Professor, Internal Medicine

Division of Hematology/Bone Marrow Transplant

University of Utah Huntsman Cancer Institute

Salt Lake City, UT

DISCUSSION QUESTIONS

• How do you decide between VRd (bortezomib [Velcade], lenalidomide [Revlimid], dexamethasone) and dara-Rd (daratumumab [Darzalex], lenalidomide, dexamethasone) for patients ineligible for transplant?
• How long do you continue treatment for?

AMANDEEP GODARA, MBBS: When we are talking about transplant-ineligible patients, a majority of the trials have looked at treatment that continues at least in some form until progression. In the clinical practice as well, patients are continuing some form of the treatment. Dose reductions once we have a good response are certainly reasonable. For patients who are having frequent interruptions because of neutropenia, dose reduction is beneficial. But, ultimately, as long as patients can continue some form of treatment, I think dara-Rd is a regimen that can work for several years in those patients. Recovery in somebody who is of an advanced stage takes its own time and these are regimens that can provide that period of time where patients can feel better [and], if they feel better immediately, can continue to feel better for a long time.

DISCUSSION QUESTIONS

• How do you determine which therapies to use in the maintenance setting?​
• For example, if you use dara-Rd, would you continue daratumumab and lenalidomide in the maintenance setting until disease progression as it was done in the MAIA trial (NCT02252172)?¹

GODARA: Do you base maintenance on the induction regimen you choose? Do you base it on patient convenience or other factors?

MUHAMMED TARAKJI, MD: I only use lenalidomide; I feel it’s convenient overall and it saves the patient office visits. I never use injection-based maintenance therapy. I always use something easy, well tolerated with minimal adverse events [AEs] and try to spare the patient the frequent visits to the office. I use lenalidomide unless there’s a contraindication or issue or progression on that.

GODARA: Even in those patients that you would treat with dara-Rd, do you generally stop the daratumumab after some time?

TARAKJI: I do, yes. I stop the dexamethasone, too. I just do the lenalidomide.

GODARA: How have patients fared, in your experience?

TARAKJI: I am even using lenalidomide alone [as induction] unless the patient is high risk. I have some [older patients] who are newly diagnosed. If they’re not high risk, I use dexamethasone and lenalidomide, and some patients can go years on that without any issues, without transplant, without anything. I usually use induction with the dexamethasone and after that I continue lenalidomide alone.

GODARA: Are you relying more on treatment holidays, so that patients have time to pick themselves up and feel better?

TARAKJI: If the patient is not asking for a holiday and they are not having AEs, I don’t necessarily put that in [if the patient is] tolerating well, meaning their blood counts are fine. I sometimes may reduce the dose. Rather than give them 25 mg, I can do 10 mg.

GODARA: When we are in a situation like this, it always helps to maybe start a bit lower there. For drug dosages, I build it up based on how patients tolerate and based on how the response is. If somebody responds to 10 mg of lenalidomide, we don’t need to go up on that dose further than that. I certainly believe in starting slow in these patients if you are in a precarious situation where you want a quick response because they are impending [risk].

Do you use supportive [management] strategies? Do you generally give intravenous immunoglobin to everybody?

TARAKJI: Unless somebody is having an infection or something, I don’t.

GODARA: I don’t feel like there’s any role for antimicrobial therapies just to prevent bacterial infections. We have a trial [ongoing].

TARAKJI: When I’m using bortezomib [Velcade] and lenalidomide, I use trimethoprim/sulfamethoxazole [Bactrim].

GODARA: Do you use Bactrim daily then?

TARAKJI: Three times a week—I use it Monday, Wednesday, and Friday. Usually, they get it in the protocol. I follow what’s on the protocol unless there’s an issue.

GODARA: Certain things are different in different practices. Sometimes I use fluroquinolones for the first few months based on the Lancet study that it improved the risk for neutropenic fevers in these patients.² But I think it’s so heterogeneous and mixed up. Some patients do so well, even better than some of our 50-year-old patients with multiple myeloma, in every respect. And there are some who from the beginning will be troubled by toxicities from their treatment. It’s such a difficult choice there beyond treatment, what kind of supportive measures [to use].

One thing I’d like to highlight is when we look at the GRIFFIN trial [NCT02874742] data, I think 10% of the patients had a blood clot in either one of the arms.³ Patients get blood clots quite frequently and they don’t necessarily have to be in the beginning of the treatment when the cancer is active, but they can have them later on as well. For any patient who can tolerate a direct oral anticoagulant, I think that goes a long way in terms of reducing the risk of having a deep vein thrombosis or a pulmonary embolism, and at least having one less problem on our hands when it comes to dealing with multiple myeloma.

_References:

_{1. Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249}

_{2. Drayson MT, Bowcock S, Planche T, et al. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol. 2019;20(12):1760-1772. doi:10.1016/S1470-2045(19)30506-6}

_{3. Sborov DW, Baljevic M, Reeves B, et al. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022;199(3):355-365. doi:10.1111/bjh.18432}