Overview of Treatments and Role of Stem Cell Transplantation for Patients With NDMM

EP: 1.Patient Profile: A 61-Year-Old Woman with Transplant-Preferred Newly Diagnosed Multiple Myeloma

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EP: 2.Overview of Treatments and Role of Stem Cell Transplantation for Patients With NDMM

EP: 3.GRIFFIN Trial: D-RVd in Transplant-Preferred Newly Diagnosed MM

EP: 4.Subgroup Analysis of MASTER Trial for Newly Diagnosed MM

EP: 5.Impact of Quadruplet Therapy on Patients with High-Risk NDMM

EP: 6.Recent Data on Other Regimens for Newly Diagnosed Multiple Myeloma

EP: 7.Unmet Needs and Advice for Community Oncologists Treating Patients With NDMM

Case: A 61-Year-Old Woman with Transplant-Preferred Newly Diagnosed Multiple Myeloma (NDMM)

• Patient ML is a 61 y/o woman.
  • PMH: Hypertension (well controlled on medication)
  • SMH: Does not smoke; drinks occasional glass of wine in social setting; Walks with friends 2-3 times weekly.

Clinical Presentation:

• In October 2022, ML visited her PCP for her annual checkup. She reported having persistent pain in her shoulders.

Clinical Workup and Diagnosis:

• Calcium 13.2 mg/dL
• LDH 600 U/L (> ULN)
• CrCl, 45 mL/min
• Hgb, 7.0 g/dL
• Beta-2-microglobulin, 6 mg/dL
• Bone marrow biopsy showed 24% monoclonal plasma cells.
• Serum monoclonal protein, 5 g/dL
• Serum kappa FLC, 200 mg/dL
• Del(17p) cytogenetic abnormalities were detected by FISH.
• PET-CT showed osteolytic lesions in the shoulders; no EMD.
• ECOG PS 1
• ML was diagnosed with ISS stage II/R-ISS stage III IgG-kappa myeloma; determined to be transplant-preferred.

Current Treatment:

• After discussions with her family and clinical team, ML was initiated on Daratumumab/bortezomib/lenalidomide/dexamethasone induction therapy (D-RVd).
• Post-induction therapy, ML achieve very good partial response (VGPR).
• Patient underwent stem cell mobilization and 3 months later underwent ASCT.
  • Post-ASCT response: VGPR

Transcript:

Natalie Callander, MD: If we’re looking here in the US [United States] at NCCN [National Comprehensive Cancer Network] guidelines, bortezomib, lenalidomide, and dexamethasone or carfilzomib, lenalidomide, and dexamethasone are really considered the top triplets. More people are turning to quadruplet regimens, such as that tested in the GRIFFIN trial (NCT02874742), meaning the combination of daratumumab, lenalidomide, dexamethasone, and bortezomib. But we’re also starting to see some data using isatuximab, primarily coming out of Europe, but there’s some here as well.

We talked a little bit about risk. I think many times people are using both carfilzomib and an anti-CD38 antibody if the patient is headed for a transplant with high-risk disease. One of the issues that come up that we try to counsel particularly with our referring physicians with these transplant-eligible patients is we know that anti-CD38 antibodies can have some impact on stem cell collection. So if we’re going to choose a quadruplet regimen like that, we pretty much want them to perhaps limit therapy to no more than 4 cycles before they’re sent to us for stem cell collection. That can be an issue. And many experts in the field will support the use of carfilzomib if the patient has no cardiovascular contraindications for high-risk or what they consider high-risk myeloma. So to use a carfilzomib-based regimen as part of induction.

I unabashedly support transplant. I have to say I’ve been doing this for a long time and one of the things [that’s important] for people who take care of a lot of transplant patients is there is that period of time when their quality of life is less than perhaps a patient going through a nontransplant regimen. But I think we know that certainly it’s been demonstrated even in the most recent DETERMINATION trial [NCT01208662] a PFS [progression-free survival] benefit of 2 years. And that’s a big deal for patients that you are not tied to a clinic. You are maybe on lenalidomide maintenance or another type of maintenance, but typically these treatments are given, at most monthly, but often patients are coming in every 3 months. I really think that has not been discussed enough, about really an improvement in quality of life for patients in that realm.

I definitely think there are some patients who probably shouldn’t consider a transplant. As we mentioned about fitness, I think if a patient is unfit, and that person could be 50 years old and unfit, maybe a transplant is not the best thing. But we do think that for patients, particularly those who now might be choosing to defer transplant, collecting those cells is still a very important idea. They may not be used necessarily for transplant, but more and more we know that patients who are going through cellular therapies, for example, CAR [chimeric antigen receptor] T-cell therapy, might want to use cells in the future for a cell boost, for example, if they’re having low count. I do think that many patients really still benefit from transplant. We certainly recommend it, and I think it’s going to take, in my mind, a lot more data to knock it off the pathway where it is included right now.

Transcript edited for clarity.