Recent Data on Other Regimens for Newly Diagnosed Multiple Myeloma

An overview of recent data from the SKylaRK and GMMG-HD7 trials evaluating non-daratumumab-based regimens for patients with transplant-preferred 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


Natalie Callander, MD: We’re very happy to see more trials come out with the approach using anti-CD38 antibodies. The GMMG-HD7 trial led by Hartmut Goldschmidt from Germany looked at a very large number of newly diagnosed patients. Around 660 patients were randomized to receive isatuximab with VRd [bortezomib, lenalidomide, dexamethasone] or VRd [bortezomib, lenalidomide, dexamethasone] alone. They did their treatment in a bit of a novel way. They did 3 blocks of 6-week treatment cycles and then went on to autologous stem cell transplantation. Then they go on to maintenance using isatuximab in that group.

What they presented were MRD [minimal residual disease] and PFS [progression-free survival] data, and they ended up showing that for probably any phase 3 trial out there, they have the highest rate of MRD negativity after induction—around 50.1%, which is quite high. This is analyzed after those three 6-week blocks of therapy, so that’s quite impressive. Their overall response rate is high. PFS data were also presented. We’re waiting for much longer and more mature data to come out, but as a start, that incorporation of isatuximab looks quite good.

SKylaRk is a much smaller study, a 50-patient phase 2 study led by Elizabeth O’Donnell. It looked at the combination of isatuximab with carfilzomib, lenalidomide, and dexamethasone, specifically in patients who are transplant eligible. It showed a response rate of 4 cycles in this particular combination, transplant induction, and a maintenance phase. Their overall response rate, I believe, is 100%. Their VGPR [very good partial response] or better rate is close to 90%. They’re doing quite well. Obviously, that’s a small study, but it’s very important. It’s going to show us that this quadruplet regimen is well tolerated.

Transcript edited for clarity.

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