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
Treatment
- Patient is ineligible for ASCT due to comorbidities
- Initiated treatment with daratumumab + lenalidomide + dexamethasone
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