Patient Profile 3: A 58-Year-Old with IgG Kappa Multiple Myeloma

Video

Experts present the case of a 58-year-old patient with IgG kappa multiple myeloma and offer their initial impressions.

Transcript:

Ola Landgren, MD, PhD: With that, it’s time to move on to the next case. Here we have a relapsed/refractory patient: a [male aged 58 years who received a diagnosis of] IgG kappa multiple myeloma. He initially presented with a left hip fracture and underwent blood testing…bone marrow biopsy…all the different types of testing. The bone marrow biopsy revealed hyperdiploid disease by the FISH [fluorescence in situ hybridization] and cytogenetics. The initial therapy for this individual was…the RVd regimen [lenalidomide (Revlimid), bortezomib (Velcade), dexamethasone]. At the time of diagnosis, the patient did not have high-risk disease [and] had a good response to therapy, and therefore the patient opted to harvest and hold the stem cells.

This patient did not want to go straight to transplant. Instead, the patient wanted to do lenalidomide, and that’s what this patient received. The patient lasted about 4 years on lenalidomide maintenance. Unfortunately, after that, there was a biochemical relapse. Then the patient was started on a combination of daratumumab with bortezomib and dexamethasone. This lasted for about 3.5 years. Again, there was a relapse. The patient was started on a combination of carfilzomib, lenalidomide, and dexamethasone. After about 8 cycles of therapy, the treatment was reduced to lenalidomide-dexamethasone for feasibility.

This is illustrating many things we have already talked about. One thing is that you can step down the intensity for feasibility. It also illustrates something that we maybe have not talked about directly but between the lines: that you can consider using drugs and reusing drugs later, in later lines. But if you have a break, maybe with some other drugs in between…then you can consider going back to similar drugs and you can use them in other combinations, such as this case. After about 2 years there was, again, a relapse and, then the patient was started on carfilzomib but now in combination with pomalidomide and dexamethasone. Unfortunately, this did not last forever. It lasted for about 2 years. There are obviously many different options. I think the NCCN [National Comprehensive Cancer Network] guideline has about 40 different combinations…and the number keeps rising. So, what will you do next, Ben?

Benjamin Diamond, MD: At this point, we have a patient [who] is penta-refractory; in other words, all the standard therapies they’ve received, they have relapsed on. We have the option now to move on to some of our more novel agents. I would urge, at least at this point, that if the patients have available to them the option that they be referred at least to consider a clinical trial, because this is the time. But if that is not available, then we have some great options in the form of CAR [chimeric antigen receptor] T-cell therapy and bispecific antibodies—most recently approved was teclistamab.

Ola Landgren, MD, PhD: That’s a great segue into what happened to this patient. This patient was started on teclistamab. That’s now available commercially here in the United States and increasingly so around the world. The patient was receiving step-up dosing in the hospital initially with 3 doses and had a grade 1 cytokine release syndrome [CRS] after the first step-up dose. This was appropriately managed in the hospital. After the first 3 step-up doses, the patient started cycle 1 outpatient once a week. After only 1 cycle of outpatient treatment, this patient is penta-refractory, has failed 3 prior lines of therapy, and now achieves a VGPR [very good partial response] with only 1 cycle of therapy. And after 3 cycles of therapy, the patient’s blood is free from protein and has a serological complete response [CR]. He is tested with a bone marrow biopsy, tested MRD [minimal residual disease] negative, 10–6 with the bone marrow biopsy. The patient now continues on teclistamab treatment single agent.

What is your thinking here, Dickran? How would you continue management with this patient? Would you keep on giving it once a week? Would you pay attention to certain things? What was your global thinking here?

Dickran Kazandjian, MD: My first thinking was, this is great for the patient. Relapsing after the 5 prior lines of therapy as mentioned, to have a CR at that line of therapy is highly impressive. I think these new immunotherapies are really setting a new precedence. But other than that, the devil is in the details. I think after a few cycles, 3 cycles, there are things, as you alluded to, that we must be careful about. I think one of the major issues is the potential [adverse] effects of infections. I think when you monitor these patients, it’s important to continuously monitor complete blood counts. See where the patient’s lymphocytes and neutrophils are, but also serum immunoglobulins to see what the IgG levels are, for example. And one must have a very short threshold to start intravenous immunoglobulins for immunosuppression that’s caused by these medications.

In terms of treatment, right now it is FDA approved, and this patient received therapy as part of the standard of care. So, of course, there is some artwork that you can always do with approved therapies. But to use it on label, you would have to continue giving it weekly. But how? I don’t know for sure. I suspect there will be a modification on the US label as we get more data. And probably there will be what we call a maintenance-like phase in these bispecific antibodies. Not so different than what we do for daratumumab, for example. But, as of today, we don’t have that.

Ola Landgren, MD, PhD: Yes, we cannot really recommend anything…

Dickran Kazandjian, MD: No, I don’t recommend it.

Ola Landgren, MD, PhD: …different from the USPI [United States Prescribing Information]. But it’s very likely that we will see longer intervals. I think until we have the data, it is a concern that could be brought up. We don’t know [whether] a patient would reexperience CRS if we wait too long. For now, I think we need to stick to the USPI, the label that the FDA has approved. But we will see what the new data show us; the trials will continue to deliver.

Dickran Kazandjian, MD: Yes, I agree.

Transcript edited for clarity.

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