Multiple Myeloma Treatment Amidst COVID-19

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Sagar Lonial, MD, FACP, focuses on the treatment of multiple myeloma during the COVID-19 pandemic, discussing the standard of care with anti-CD38 monoclonal antibodies and daratumumab.

Sagar Lonial, MD, FACP: One of the challenges we have all struggled with in the last year has been how COVID-19 [coronavirus disease 2019] infections have impacted the treatment of myeloma. It has been a bit like a pendulum. Early on, we swung way in favor of sort of minimizing therapy, reducing dose intensity, minimizing any visits to the infusion center. While I think that was an appropriate approach, given that we had a lot of unknowns with COVID-19 and myeloma early on, I am not sure that ultimately benefitted our patients.

What we are seeing now with longer follow-up—as well as follow-up from some of our colleagues in New York who were impacted pretty significantly, but in many ways continued therapy—is that the biggest risk factor for poor outcome, if you are a patient with myeloma with COVID-19, is significant disease burden. So, it is important to do whatever you can to try and reduce disease burden. If that means treating with dose-intense therapy, then that is OK, because there is nothing more immunosuppressive to a patient with myeloma than lots of myeloma.

Another thing that we have identified is trying to potentially whittle off some of the doses of dexamethasone. For example, perhaps only going with 40 mg a week in the first dose or 2 and then trying to reduce the dexamethasone. In many situations, we have tried to reduce the frequency of daratumumab infusions from every week or every other week to once a month. Again, I would keep an eye on efficacy. If you are early in treatment and there is a lot of myeloma burden in the body, I do not know if reducing the frequency of daratumumab is the right answer, until you get good disease control. Once you have good disease control, then trying to minimize the impact of immunosuppressive therapies makes good sense. Until that occurs, I would suggest continuing intensive therapy to the best of your ability to try and get good disease control.

I think it is clear that the CD38 antibodies are a pretty significant and important therapeutic option for patients with myeloma at all different stages. They have now become part of the standard of care for myeloma in the newly diagnosed setting, in the early relapsed setting, and are often used in the refractory/relapsed settings as well. I do not know that the COVID-19 pandemic really changes the role of CD38, except that it is one way to quickly get responses and reduce disease burden. We know that reducing disease burden allows normal immune function to return, and that ultimately helps our patients in the short term and long term.

In summary, daratumumab really does offer significant benefit. I would not necessarily attenuate the dose unless patients have good disease control. Also, do not be afraid to use daratumumab in the context of COVID-19. Again, I think the best defense we can have for our patients is a good healthy immune system, and getting rid of myeloma is the first step to getting there.

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

Treatment

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