Treatment Options After Fourth-Line Therapy in TCR MM


Dr Adriana Rossi reviews the therapeutic options for patients with triple-class refractory multiple myeloma in terms of mechanism of action and safety profile.

Adriana Rossi, MD: Patients like this who’ve progressed on 4 prior lines of therapy have very limited options. Certainly consideration for a clinical trial would be advised. If they have access to either an academic center or otherwise are able to participate in clinical trials, that is always a good option. But especially given her age, and we don’t know about her comorbidities, I think the option of belantamab was a very good one, not only because this is exactly the population that we’ve studied, but it is a very tolerable and very effective therapy for this patient population.

Belantamab mafodotin is an antibody-drug conjugate that targets BCMA. It carries a toxic payload known as MAF, which is known to cause ocular toxicity. I think it’s the first antibody-drug conjugate, or ADC, that we have available in myeloma. It’s also the first BCMA-targeted therapy. Both of these make it a very exciting option. It does come with the unique ocular toxicity, which has gotten quite a bit of attention. But interestingly, I have a number of patients who have tolerated it. About half of patients will go on to develop ocular toxicity, but the vast majority will improve with dose delays or dose reductions. Just as in the clinical trials, my experience has also been that maybe the dosing was a little optimistic. And if we dose it less frequently or at a reduced dose, we can get patients to stay on therapy for much longer. The schedule, which is once every 3 weeks, is something patients really appreciate.

The current treatment the patient is on, selinexor, is another recent addition to our armamentarium. In this case, it is an XPO inhibitor, which is a nuclear transport. So, it’s a protein that the cells use to get rid of tumor suppressors and growth factors. And by inhibiting them, these accumulate in the nucleus and lead to cell death. The drug is oral, which I think is one of the big selling points, especially in this past year, with reducing visits to the office. It was a good time to have it added to our menu of options, but it does come with significant toxicity itself, namely central nausea. So, patients usually require a number of antiemetics. There again, I think approval on the studies started with maybe an optimistic dosing of twice a week. As we’ve moved through different studies and different combinations, I think we’ve learned that once-a-week dosing makes it much more tolerable, and dose reducing as necessary. Again, not all patients will be able to tolerate the full dose as approved.

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

Related Videos
Yi-Bin Chen, MD, an expert on GVHD
Yi-Bin Chen, MD, an expert on GVHD
A panel of 3 experts on GVHD
Related Content