Considerations for Treatment Selection After Fourth-Line Therapy in TCR MM


Dr Adrianna Rossi reviews considerations for treatment selection in the triple-class refractory setting in patients with multiple myeloma.

Adriana Rossi, MD: In a patient who is triple-class refractory, their standard of care options are certainly limited. It’s important at every junction, once myeloma relapses, to take into consideration the patient. What comorbidities do they have? Was is their access to the clinic, their schedule, ability to sit in a chair, ability to tolerate oral medications? Also, it’s important to identify the relapse, so certainly, always having a bone marrow biopsy to identify potentially new cytogenetic changes, as was the case in this patient. And use disease characteristics, which could then influence drug selection. In addition to that, we have now their history. So, what drugs have they been exposed to? How well did they respond to them, but also, how well did they tolerate them? Knowing that this patient has renal compromise at this time makes a rapid response highly desirable. We don’t know her comorbidities, but those should play into it, and the prior toxicities.

We know which agents she’s had and the response she was able to get, but were any of those limited due to toxicity? Was she able to stay on continuous therapy for all of those lines? Were they interrupted? Were there relapses while she was off drug? These are all important considerations. Having a drug that has nonoverlapping toxicity to her previous medications, I think is important. Having a schedule that she can keep to, again, even if it is not the first plan, whatever the schedule is established to be. And again, always considering clinical trials. I think the ability to expand that menu of options is really valuable, especially in this population.

Transcript edited for clarity.

Case: A 75-Year-Old Woman with Triple-Class Refractory Multiple Myeloma

Initial Presentation

  • A 75-year-old woman diagnosed with multiple myeloma 5 years ago returns to the clinic with complaints of extreme fatigue, increased muscle weakness and new bone pain in her right hip, right forearm and low back. She reports that she is currently taking antibiotics for a bacterial infection, her third in the last 12 months.
  • Treatment history:
    • Initially treated with DRd; CR lasting 20 months
    • Switched to VRd, stable disease lasting 16 months
    • Subsequently switched to KPd, achieved a PR lasting 12 months
    • Started selinexor; follow up at 9 months showed M protein increase by 0.5 g/dl; patient continued to feel well 
  • Currently, 3 months after her last visit, she returns to the clinic for follow-up
  • PE: new bony tenderness appreciated on right hip, pelvis forearm and lumbar spine; bruising and mild bleeding of the gums

Clinical Workup

  • Labs: Hb 6.2 g/dL, calcium 8.4 mg/dL, LDH 160 U/L, creatinine 2.1 mg/dL, albumin 2.7 g/dL, b2 microgloblulin 4.9 mcg/mL, serum M-protein 4.2 g/dL, lambda free light chains 4.1 mg/dL
  • HBV negative
  • Skeletal survey and MRI revealed lytic bone lesions in the left hip, pelvis and L2 vertebrae and lytic lesions as well as a hairline fracture in the distal radius of the right arm
  • Bone marrow shows 62% plasma cells IgG k
  • FISH: t(11;14) at diagnosis; new del(17p)
  • Diagnosis: R-ISS stage II MM
  • ECOG 1


  • Initiated treatment with belantamab mafodotin

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