Video
Patient Scenario 2: A 57-Year-Old With Heavily Pretreated MM
Moving on to the second clinical scenario of multiple myeloma, Luciano Costa, MD, details his care of a heavily pretreated patient.
Transcript:
Luciano Costa, MD: If it’s OK, I can proceed with bringing up the second case. This is a patient I have known for a number of years now. The patient is a 57-year-old Black veteran who presented 10 years prior to this decision point, with bone pain and bone lesions. At the time he was diagnosed with IgA [immunoglobulin A] myeloma, ISS [International Staging System] stage II, and had hyperdiploidy by FISH [fluorescence in situ hybridization]. I will not bother you with all his prior therapies, but before he met me, he had received 7 prior lines that include essentially all the 3 proteasome inhibitors: lenalidomide, pomalidomide, daratumumab. He had received 2 autologous transplants and had received a prior allogeneic transplant. His most recent line of therapy had been combination chemotherapy. It got to the point where his disease was active and none of the conventional agents were working, and he received what we call modified hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. He had a very brief partial response that was followed shortly after with his progression.
When I met the patient, he had progressive disease, and he had worsening hip pain, but he still had a good performance status. He had an ECOG score of 1, he had measurable paraprotein, and had great cardiac, renal, hepatic function. His bone marrow had 20% plasma cells. Similarly to Dr Rossi’s case, over the years, his myeloma had acquired a deletion of chromosome 17p, on top of the background of hyperdiploidy. I show his PET [positron emission tomography] scan because it’s quite interesting when you see what happened. He had several areas of extramedullary disease, had a big lesion in the liver that is shown there, had a lesion in the peritoneum that is not shown, and he had a lesion on the hip that was an extension yet adjacent to the bone, but clearly with a big element of soft tissue that was palpable on the physical exam. The patient was found to be eligible for a trial with a CD3/GPRC5D bispecific antibody. During therapy, he developed grade 1 CRS [cytokine release syndrome] during the step-up dosing, but there was no more CRS beyond the intended target dose. He did not have any infectious complication, but had transient grade 3 neutropenia that responded promptly with growth factor. After 2 cycles, he had a partial response. The assessment included a repeating PET scan. I have shown here those 2 areas that I showed initially, and you can see a very distinct difference in responses.
Essentially, the peritoneal lesion that I’m not showing here shrank. The liver lesion is about the same, slightly smaller. But the hip lesion, the lesion adjacent to the bone, had completely resolved, which I find quite interesting. We know for a fact that as myeloma evolves, you have different subclones, and it has been elegantly demonstrated that the disease biology can be quite different in one area versus another. This case exemplifies that very well. Somehow the disease that was on his pelvis was very responsive, but not the disease that was in the liver or in the peritoneum. The patient did well and continued therapy, but he then had disease progression during cycle 6. At that point, he had a complete resolution of all the toxicities from prior treatment. He still had a good performance status and good organ function. He was a very ambitious, trusting man who wanted to do what it takes to be well and to stick around for his family.
He agreed to participate in a phase 1 trial of an experimental anti-BCMA [B‑cell maturation antigen] CAR [chimeric antigen receptor] T-cell treatment. He successfully collected cells. We decided not to use bridging therapy. There was hardly anything that would be wise to use in somebody with such a refractory disease, but he tolerated lymphodepletion very well and tolerated infusion. He developed grade 1 CRS post-CAR T that was treated with tocilizumab. He did not have any neurological toxicity. He again had some grade 3 neutropenia and thrombocytopenia that was transient and did not require any intervention. At the end of the first month, the patient had a partial response. Toward the end of month 3, he had disappearance of the paraprotein. We couldn’t call him complete response [CR] yet because he still had abnormalities on a PET scan, but as you can see on the pain on the right, those abnormalities gradually became smaller and smaller and completely disappeared by month 9. Currently, the patient is in stringent CR 12 months after CAR T therapy, with an ECOG score of 0 and no ongoing toxicities.
Transcript edited for clarity.
