Challenges and Unmet Needs in the Treatment of Multiple Myeloma

Sagar Lonial, MD, FACP, summarizes current challenges and his hopes for the future concerning the treatment of multiple myeloma.

Sagar Lonial, MD, FACP: As we begin to think about the future of myeloma therapy and where we are now, it is a bit of a puzzle. We have so many new drugs, new combinations. In phase 1 studies, we probably have 3 or 4 new bispecifics. The treatment landscape and management of myeloma is becoming more complicated.

What I look forward to in the future is combinations of immune targets, where we can really reduce the disease burden significantly. As we do that, we can begin to talk about getting away from the current model of continuous therapy and heading more toward the model of intensive therapy that induces MRD [minimal residual disease] negativity. And ultimately, we can begin to think about discontinuation of therapy. That’s not something we have been able to reliably do, because early time points of MRD negativity don’t always correlate with late time points of MRD negativity. Ultimately, it is sustained MRD negativity that really has the biggest impact on patient outcomes. So, I think we need to figure out how to understand all these things together.

More importantly, as this gets more confusing for myeloma experts, it is going to get more confusing for community doctors who deal with many different diseases at the same time. And so, one of the key recommendations I always make is to find that myeloma expert who you philosophically agree with and partner with him or her, in terms of how to best treat your patients. That does not mean that your patients have to be sent to a tertiary center for every visit or that all of their care has to be delivered there, but I think partnering with an expert at a myeloma center is very important. That can be done via telehealth; it can be done via phone calls. Many of us are happy to share patients with doctors who can care for their patients in their own environment but make sure they have access to the latest and greatest technologies, greatest access to clinical trials, and ultimately the most recent approaches to management of myeloma in every stage of their disease. If we make that partnership effective, we will have raised the level of care for myeloma around the country and can improve outcomes for our patients.

Transcript edited for clarity.

Case: A 78-Year-Old Man with Multiple Myeloma

Initial Presentation

  • An active 78-year-old man presents with a year history of progressive fatigue; he feels joint and muscle pain diffusely for about 2 months
  • PMH: suffered a myocardial infarction 4 years ago; LVEF 45%
  • PE: bony tenderness appreciated on the hips and lower back

Clinical Workup

  • Labs: Hb 10.9 g/dL, calcium 10.0 mg/dL, LDH 160 U/L, creatinine 2.1 mg/dL, albumin 3.3 g/dL, beta-2 microgloblulin 5.2 mcg/mL, M-protein 2.6 g/dL, lambda free light chains 4.1 mg/dL
  • Hepatitis B negative
  • Skeletal survey and MRI revealed lytic bone lesions in the left hip, pelvis and L2 vertebrae
  • Bone marrow shows 70% plasma cells IgG k restricted
  • FISH: normal
  • Diagnosis: R-ISS stage II MM
  • ECOG 0


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