First-Line Treatment Options and Subsequent Risks Facing Multiple Myeloma Patients


Saad Usmani, MD, discusses what first-line options are available for patients with multiple myeloma while highlighting the difficulties in defining high-risk characteristics associated with multiple myeloma.

Saad Usmani, MD: The way we approach taking treatments for patients with myeloma is by looking at patient-related factor and disease-related factors, and then obviously patient preference plays a role.

Performance status, comorbidities, and patient age are important factors. Comorbidities are also important: hypertension, corneal renal artery disease, diabetes, and other end-organ damage, such as renal insufficiency or for neuropathy. Significant cardiac diseasesare going to be important issues. Patients’ level of activity is going to be important. And from a disease perspective you must see if the patient has any high-risk features, because that influences the choice of treatments.

For a transplant-ineligible patient with revised ISS [insulin sliding scale] stage II disease without any high-risk features, the options would be to go for a VRd [bortezomib,lenalidomide, dexamethasone]–light approach or DRd [daratumumab, lenalidomide, dexamethasone] approach.

For this patient, my preference would be for DRd [daratumumab, lenalidomide, dexamethasone], given that she already has neuropathy. We are seeing phenomenal ongoing results with the MAIA clinical trial, which was a randomized phase 3 study that had looked at DRd [daratumumab, lenalidomide, dexamethasone] vs Rd [lenalidomide, dexamethasone] combination for patients such as this.

Defining high risk in multiple myeloma is a challenge because you must consider disease burden as well as disease biology. There are some certain phenotypes or circulating plasma cells at the time of diagnosis or high-burden disease with venal insufficiency, which can impact survival outcomes. whereas there are other specific karyotype and FISH [fluorescence in situ hybridization] abnormalities, like chromosome 1q21 abnormalities, both gain amplification. Having 3 copies is called gain and having 4 or more copies of 1q21 is called amplification. Then having deletion 17p and translocation 1416 or 1420 are high-risk features.

We also consider translocation 4;14 outside the United States as a high-risk feature. But in the United States, because of the incorporation of proteasome inhibitors, the majority of translocation 4;14 patients do better than expected for a high-risk patient in the year 2020.

Transcript edited for clarity.

Case: A 75-Year-Old Woman With Multiple Myeloma

Initial Presentation

  • An active 75-year-old woman presented with new onset back pain and a 10-month history of fatigue, mild sensory neuropathy
  • PMH: hypercholesterolemia, diabetes, and atrial fibrillation; all medically controlled
  • PE: bony tenderness appreciated on the hips and lower back

Clinical Workup

  • Labs: Hb 10.2 g/dL, calcium 11.1 mg/dL, LDH 186 U/L, creatinine 1.3 mg/dL, albumin 3.7 g/dL, beta-2 microgloblulin 3.6 mcg/mL, potassium 1100 g/dL, M-protein 2.6 g/dL, lambda free light chains 4.1 mg/dL
  • Hepatitis B and C negative
  • X-ray showed L4 vertebral compression fracture
  • Skeletal survey showed multiple lytic lesions in femur
  • Bone marrow shows 40% clonal plasma cells IgG k with hyperdiploidy FISH
  • Diagnosis: R-ISS stage II MM
  • ECOG 1


  • Patient is ineligible for ASCT due to comorbidities
  • Initiated treatment with daratumumab + lenalidomide + dexamethasone
Related Videos
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Jamie Koprivnikar, MD, and Hana Safah, MD, experts on MDS
Related Content