Peter Voorhees, MD, presents a case of a 63-year-old man with R/R multiple myeloma, shares his initial impressions, and discusses the assessment of clinical relapse in patients with R/R multiple myeloma.
Case: A 63-Year-Old Man with R/R Multiple Myeloma
Clinical Presentation:
Patient AG is a 63 y/o man.
Clinical Workup and Diagnosis:
Disease Relapse and Treatments:
Peter Voorhees, MD: Hello, my name is Peter Voorhees. I am the chief of the Plasma Cell Disorders Division at Levine Cancer Institute in Charlotte, North Carolina. Welcome to Targeted Oncology™ Case-Based Peer Perspectives, and today we’re going to be discussing a 63-year-old patient with relapsed and refractory multiple myeloma.
The patient has a past medical history of type 2 diabetes mellitus and hypertension. They do not smoke or drink. In October of 2018, this patient was admitted from the clinic with hypercalcemia and anemia after a right pathologic hip fracture. As far as work-up is concerned, the calcium level was 11.7 mg/dL, the M protein was 2.1 g/dL, and hemoglobin 11.2 g/dL. The patient had an elevated LDH [lactate dehydrogenase] diagnosis. The albumin was 2.7 g/dL, and the beta 2 microglobulin was 6.8 mg/L. A bone marrow biopsy demonstrated 25% clonal plasma cells, and a multiple myeloma FISH [fluorescence in situ hybridization] panel revealed the presence of a deletion 17p.
A PET [positron emission tomography]-CT scan was performed. It 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 was initiated on bortezomib, lenalidomide, and dexamethasone induction therapy as part of frontline treatment.
This patient relapsed multiple times 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 prior lines of therapy. The treatment was started at a dose of 0.4 mg/kg, every week, subcutaneously.
The most important question is: What is this patient’s prognosis following relapse after belantamab mafodotin? The truth is we don’t fully understand yet. We know that patients with what we call triple-class refractory multiple myeloma do not have a good prognosis, and specifically, this refers 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 in that particular group of patients that the median overall survival is less than 1 year. This is a patient who has then gone on to a BCMA-targeted therapy, specifically belantamab mafodotin, and has progressed beyond that, so this is the quadruple-class refractory patient population. Presumably, the prognosis is going to be even worse than for those with triple-class refractory disease, and clearly, there’s an unmet need here.
This patient was started on talquetamab, presumably in the context of a clinical trial, and this is a decision with which I agree 100%. There are emerging data on the use of other BCMA-directed therapies, after relapse from a prior BCMA-targeted therapy, so we do know there is activity of the BCMA-targeted bispecific antibodies after a BCMA-directed antibody-drug conjugate such as belantamab mafodotin. We also know that there is activity of BCMA-directed CAR [chimeric antigen receptor] T-cell therapy after belantamab mafodotin. However, the results that we’re seeing with both 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 particular situation is very appropriate, and talquetamab binds a novel cell surface marker on multiple myeloma cells called GPRC5D.
When I’m assessing patients for worsening of their disease, I typically use the International Myeloma Working Group Uniform Response Criteria. And there are different types of disease progression. There is what we call biochemical progression, which is simply a worsening of the markers, whether the patient is measurable by M [monoclonal]-spike determination on protein electrophoresis, or whether they’re more appropriately monitored by, say for example, serum free light chain testing.
Then there’s what we call clinical relapse, which is emergence of new clinical symptoms and signs indicative of worsening disease, and this may be worsening anemia that’s directly attributable to the advancement of the multiple myeloma as opposed to other causes. It may be the development of a new bone lesion or a new extramedullary plasmacytoma. It may be the progression of existing bone lesions or existing plasmacytomas, the emergence of new renal failure directly attributable to the progression of the multiple myeloma, or new hypercalcemia as a result of progressive bone disease from advancing multiple myeloma.
The distinction between biochemical progression vs clinical relapse is important because a patient with clinical relapse has active signs of disease and needs new therapy right away. A patient with a biochemical progression, particularly if it’s a slowly moving biochemical progression, has a bit more latitude as far as treatment options are concerned. And a patient in biochemical progression may be a better candidate for CAR T-cell therapy when you can’t get your hands on definitive therapy immediately, whereas someone with a clinical relapse would probably be better afforded treatment with an off the shelf product such as a bispecific antibody.
Transcript edited for clarity.
Care Teams Ease Inpatient/Outpatient Transitions in Multiple Myeloma
December 5th 2024Patients with multiple myeloma face a complex, decades-long treatment journey involving care coordination, insurance challenges, and multiple providers, highlighting the need for comprehensive care plans to ensure optimal outcomes.
Read More
FDA Accepts BLA for Belantamab Mafodotin Combinations in R/R Multiple Myeloma
November 25th 2024The FDA has accepted the BLA for belantamab mafodotin in combination with bortezomib and dexamethasone, or pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma, as supported by DREAMM-7 and DREAMM-8 data.
Read More
Real-World RRMM Data Explore Dose Deescalation and Outpatient Use of Teclistamab
November 18th 2024During a Case-Based Roundtable® event, Hana Safah, MD, examined several real-world studies of dose frequency and outpatient administration of teclistamab in patients with multiple myeloma in the first article of a 2-part series.
Read More