The Role of Maintenance Daratumumab in Transplant-Eligible Multiple Myeloma

Brea C. Lipe, MD

Clinical Director, Multiple Myeloma Program

Associate Professor, Department of Medicine

Wilmot Cancer Institute

University of Rochester Medical Center

Rochester, NY

CASE SUMMARY:

• A 54-year-old woman presented to her physician with the following laboratory results:
• Hemoglobin: 7.0 g/dL
• β2-Microglobulin: 6 mg/dl
• Albumin: 3.2 g/dL.​
• Calcium: 11.3 mg/dL
• Lactate dehydrogenase: 200 U/L
• Creatinine clearance: 45 mL/min​
• Bone marrow: 22% clonal plasma cells​
• Serum κ free light chain : 24 mg/dL​
• Serum monoclonal protein: 5 g/dL​

She had no cytogenetic abnormalities based on fluorescence in situ hybridization and karyotyping. Her EGOG performance score was 1. A PET-CT scans showed multiple bone lesions in vertebrae​. She wasdiagnosed with IgG-κ multiple myeloma, revised International Staging System II,​ and was identified as being transplant eligible.

Dara-VRd (Daratumumab [Darzalex], bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone) induction therapy was initiated​. She achieved very good partial response (VGPR) post induction therapy​. She underwent stem cell mobilization and 2 months later underwent autologous hematopoietic stem cell transplant (ASCT)​. Post-ASCT response was a VGPR​.

DISCUSSION QUESTIONS:

• How do you manage adverse events (AEs) for patients receiving induction therapy? Does it differ for triplet versus quadruplet therapy? ​
• What are the available treatment options for patients with transplant-eligible multiple myeloma in the consolidation and maintenance setting?​
• Does your choice of induction therapy impact your choice of consolidation and maintenance therapy in patients with transplant-eligible multiple myeloma?​
• What is your approach toward maintenance therapy for patients who receive a quadruplet regimen?​

BREA C. LIPE, MD: If you’re using a quadruplet up front, how do you work the maintenance in? Do you continue the daratumumab? Do you stop the daratumumab?

MARC BRAUNSTEIN, MD: I tend to continue the daratumumab. There was a randomized study looking at [maintenance] daratumumab versus lenalidomide plus daratumumab [DRAMMATIC; NCT04071457], but I tend to follow the GRIFFIN study [NCT02874742].¹ You could argue that giving lenalidomide alone will avoid [the patient becoming] refractory to daratumumab on progression. But if you compare it with the MAIA study [NCT02252172] of daratumumab, lenalidomide, and dexamethasone, which has shown a survival benefit with adding daratumumab, I think you’re more likely to get a benefit of continuing it as maintenance.^2,3

LIPE: There are some PFS2 [time to second disease progression] data.⁴ One of the things I point out to my patients is the options for relapse treatment are much different today than they were 10 years ago. So, even when patients are relapsing, if the addition of something like daratumumab gets me so much further down before they relapse, then my treatment options will be even greater.

BHUVANA RAMKUMAR, MD: I’ve used the quadruplet regimens, and I’ve been comfortable using the daratumumab maintenance but only in 1 patient in the last year or so, and she had vision issues. Every time I give daratumumab, she’ll say she has blurry vision for a few days. I’ve asked other experts, too. I don’t know if anybody else has any experience with vision issues with daratumumab. We had to stop it during the maintenance time, and the vision got better when we stopped, so that was the only case. But, otherwise, they usually do OK and I continue.

LIPE: Were you giving the dexamethasone with the daratumumab still in the maintenance setting?

RAMKUMAR: No, in the maintenance setting I tapered off and stopped the dexamethasone. Do you think that could help?

LIPE: I have patients who get the vision changes from the dexamethasone related to fluid status. Even with lenalidomide, I have some patients who over time [have vision issues]; and I always find it hard to know their vision is getting worse but they’re also now 5 years older. I have had patients complain of vision problems, but I find it difficult; is it the lenalidomide; is it the daratumumab? If you stopped the daratumumab and it got better, it’s pretty clear.

RAMKUMAR: At first, I didn’t believe what she was saying. I took her off the dexamethasone, but it still didn’t get better. Then…I stopped [the daratumumab] and it got better.

LIPE: Yes. So, for physicians who aren’t using daratumumab up front, are you using lenalidomide maintenance for everybody, for certain patients, or do you ever consider a different maintenance option? If you start with the quadruplet, do you do the daratumumab/lenalidomide maintenance for everybody or is it only certain patients?

IGOR GENKIN, MD: In this case I would probably use both for maintenance. However, I haven’t used daratumumab much for maintenance. I’ve been using more lenalidomide because that’s what we had in the past. If I have to use quadruplet at the beginning, then perhaps I will consider doublet [maintenance] as well.

LIPE: The National Comprehensive Cancer Network [NCCN] guidelines [prefer lenalidomide as maintenance, but also recommend ixazomib (Ninlaro) and bortezomib].⁵ But I find that I don’t need to use these as much for maintenance, so I haven’t had a problem. If I couch it as ongoing therapy and not maintenance, then I can pretty much do it. I have found that I can do whatever I want to do in the maintenance setting. I just don’t call it maintenance; I call it ongoing therapy for residual disease.

RAMKUMAR: Why wasn’t [daratumumab] included in the NCCN guidelines? Are they waiting for more data or more time? Because everybody is using it [now], right? It’s good to have it, so we don’t have to say it is ongoing [therapy]. Because sometimes we have to explain and change our note.

LIPE: I think there’s a heightened awareness and concern about financial toxicity when we’re continuing these drugs longer. I’m not on the NCCN guidelines panel, but I have heard that that weighs in and that might sway what’s on this maintenance setting. I found it strange that they include ixazomib but not a daratumumab-based combination.

_References:

_{1. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288}

_{2. 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}

_{3. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596. doi:10.1016/S1470-2045(21)00466-6}

_{4. Kumar SK, Tacon T, Usmani SZ, et al. Updated analysis of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM): the phase 3 Maia study. Blood. 2029;136(suppl_1):24-26. doi:10.1182/blood-2020-134847}

_{5. NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2023. Accessed October 5, 2022. https://bit.ly/2T0mDYS}