Impact of Quadruplet Therapy on Patients with High-Risk NDMM

Video

Natalie Callander, MD, details findings from her study, evaluating the impact of quadruplet therapy on newly diagnosed patients with high-risk multiple myeloma.

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: I was very happy to be the head of a group composed of GRIFFIN and MASTER investigators. We pooled our data to see the impact of these quadruplet regimens on the outcome of patients with high-risk cytogenetics. We found out that in both studies there were somewhat more high-risk patients in the MASTER trial because it was amended to enrich for those patients. In both studies, the high-risk patients—those who had 2 or more high-risk cytogenetic abnormalities—were benefiting but at a lower rate.

Initially, their MRD [minimal residual disease]–negativity rate was fine, but we got there. Over time, they had a deterioration. With a several-year follow-up, we were seeing that only 60% of patients in both studies were remaining MRD negative. Both were consistent in 2 different approaches with these quadruplet regimens, but they signal that we need to do more for patients with 2 or more cytogenic abnormalities, either in the induction part or more likely in the maintenance phase—perhaps the addition of longer therapy or more or novel drugs in that area.

Transcript edited for clarity.

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