63-year-old patient with relapsed-refractory multiple myeloma (R/R)

Case: 63-year-old male with R/R Multiple Myeloma

Clinical presentation:

Patient AG is a 63-year-old male.

  • HMP: Diabetes, Hypertension
  • SMH: Does not smoke or drink alcohol
  • In October 2018, AG was admitted to the clinic with hypercalcemia (Ca 13.7) and anemia (Hb 10.6) after a pathological fracture of his right hip.

Clinical Evaluation and Diagnosis:

  • Calcium: 11.7 mg/dL
  • M protein, 2.1 g/dL
  • Hemoglobin: 11.2 g/dL
  • high LDH
  • Albumin, 2.7 g/dL
  • SCr, 1.3 mg/dL
  • Bone marrow biopsy confirms 25% clonal plasma cells, FISH del(17p)
  • PET-CT confirms osteolytic bone lesions in both hips; SF diagnosed with IgG kappa multiple myeloma

Disease relapse and treatments:

  • AG was started on VRd (bortezomib, lenalidomide, and low-dose dexamethasone) at the frontline
  • He subsequently relapsed and progressed on 3 lines of therapy including belantamab mafodotin
  • He was then enrolled in a clinical trial and started on treatment with the bispecific antibody, talquetamab following four previous lines of therapy.
  • Talquetamab was started at a dose of 0.4 mg/kg weekly SC

Peter Voorhees, MD: Hello, my name is Peter Voorhees. I am the Chief of the Division of Plasma Cell Disorders at the Levine Cancer Institute in Charlotte, North Carolina. Welcome to Targeted Oncology™ Case-based peer perspectivesand today we’re going to discuss a 63-year-old patient with relapsed and refractory multiple myeloma.

The patient has a medical history of type 2 diabetes mellitus and hypertension. They don’t smoke or drink. In October 2018, this patient was admitted to the clinic with hypercalcemia and anemia after a pathological fracture of the right hip. As for the investigation, the calcium level was 11.7 mg/dL, the M protein was 2.1 g/dL and the hemoglobin was 11.2 g/dL. The patient had an elevated LDH [lactate dehydrogenase] diagnosis. Albumin was 2.7 g/dL and beta 2 microglobulin was 6.8 mg/L. A bone marrow biopsy demonstrated 25% clonal plasma cells and a FISH multiple myeloma [fluorescence in situ hybridization] panel revealed the presence of a 17p deletion.

A PET [positron emission tomography]-Tomography was performed. Demonstrated osteolytic bone lesions in both hips. Ultimately, this patient was diagnosed with Revised-ISS [International Staging System] stage III, IgG kappa multiple myeloma. The patient started induction therapy with bortezomib, lenalidomide and dexamethasone as part of the initial treatment.

This patient had multiple relapses and progressed on 3 lines of therapy including belantamab mafodotin, the BCMA-targeted antibody-drug conjugate. The patient was then started on treatment with the bispecific antibody talquetamab following 4 previous lines of therapy. Treatment was started at a dose of 0.4 mg/kg, weekly, subcutaneously.

The most important question is: What is the prognosis for this patient after relapse after belantamab mafodotin? The truth is, we still don’t fully understand. We know that patients with what we call triple class refractory multiple myeloma do not have a good prognosis, and specifically this is referring to patients who have a disease that has become resistant to at least 1 of the proteasome inhibitors, at least 1 of the immunomodulatory drugs and at least 1 of the CD38 monoclonal antibodies. We know that in this specific group of patients the median overall survival is less than 1 year. This is a patient who crossed over to a targeted BCMA therapy, specifically belantamab mafodotin, and progressed beyond that, so this is the quadruple class refractory patient population. Presumably, the prognosis will be even worse than for those with triple-class refractory disease, and clearly there is an unmet need here.

This patient was started on talquetamab, presumably in the context of a clinical trial, and this is a decision I 100% agree with. There are emerging data on the use of other BCMA-targeted therapies after relapse from a prior BCMA-targeted therapy, so we know that there is bispecific BCMA-targeted antibody activity following a BCMA-targeted antibody-drug conjugate such as belantamab mafodotin. We also know that there is BCMA driven CAR activity [chimeric antigen receptor] T-cell therapy after belantamab mafodotin. However, the results we are seeing with bispecifics and CAR T cell therapy in patients previously exposed to BCMA-targeted therapy are not as robust as those who have not received prior BCMA-targeted therapy. So I think going against another target in this specific situation is very appropriate, and talquetamab binds to a new cell surface marker on multiple myeloma cells called GPRC5D.

When I am evaluating patients for worsening of their disease, I usually use the International Myeloma Working Group’s Uniform Response Criteria. And there are different types of disease progression. There is what we call biochemical progression, which is simply a worsening of markers, whether the patient is measurable by M [monoclonal]- determination of peaks in protein electrophoresis or whether they are more adequately monitored, say, for example, serum free light chain test.

Then there is what we call clinical relapse, which is the emergence of new symptoms and clinical signs indicative of worsening disease, and this could be worsening anemia directly attributable to advancing multiple myeloma as opposed to other causes. It could be the development of a new bone lesion or a new extramedullary plasmacytoma. It could be progression from existing bone lesions or existing plasmacytomas, the emergence of new renal failure directly attributable to progression of multiple myeloma, or new hypercalcemia as a result of the progressive bone disease of advanced multiple myeloma.

Distinguishing between biochemical progression and clinical relapse is important because a patient with clinical relapse has active signs of disease and needs new therapy immediately. A patient with a biochemical progression, especially if it’s a slow biochemical progression, has a little more latitude when it comes to treatment options. And a patient in biochemical progression may be a better candidate for CAR T cell therapy when you can’t get definitive therapy right away, whereas someone with a clinical relapse would likely be better treated with an off-the-shelf product like a bispecific antibody.

Edited transcript for clarity.

63-year-old patient with relapsed-refractory multiple myeloma (R/R)

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