A complex case study in multiple myeloma management, exploring treatment sequencing options for a patient with a long history of disease and multiple lines of therapy.
Sagar Lonial, MD, FACP: Well, I think we’ve set the stage now for the next discussion topic, which is sequencing, the million-dollar question. So, Dr Costa, do you want to start us off with a case to whet our appetite?
Luciano Costa, MD: So, I have this patient in our practice, she has been there longer than I have. She [received a diagnosis aged 51 years]…in 2010. At that point, she had an ISS2 multiple myeloma with some bone disease, had a very small M spike, 0.7. But the most measurable parameter was free kappa light chain. And of course, the urine, Bence-Jones proteinuria. She had bone marrow…[with] quite a bit of infiltration, 50%. It had a monosomy 14. It was the only cytogenetic abnormality. And the patient was very healthy, working full time.
…[S]he received therapy with RVd [lenalidomide, bortezomib, and dexamethasone] for 4 cycles, obtained a PR [partial response], had a transplant with the melphalan 200 [mg/m2]. But [she] did not proceed with maintenance therapy. I think it was patient’s choice and, maybe 13 years ago, was not as much of a fixture as it is nowadays. And this patient did quite well, I think by our accounts particularly considering she didn’t receive maintenance therapy. I met her in 2015. She had some resurgence of the paraprotein, 0.3, which is not a lot, but it’s a lot for somebody whose initial diagnosis was 0.7 with a lot of bone disease. So, we respect that. And a kappa light chain of 354. And then she received therapy again with RVD, had only a minimal response.
We changed to KCd [carfilzomib, cyclophosphamide, and dexamethasone], obtained a PR after 3 cycles. And then we did the second transplant, considering that she was a young patient and still had cells in storage and had a very long remission after the first transplant. And then we continued carfilzomib post therapy, because that was the agent that had a good response to prior to transplant. And she tolerated it quite well, continued to work. She was actually a school librarian.
In 2019, she again has biochemical progression. At that point she, we have monoclonal antibodies on the market. She had not yet been exposed. She was coming out of a proteasome inhibitor-based therapy. So, we did what I think was the most intuitive thing, is we treated her with daratumumab, pomalidomide, and dexamethasone. And she did quite well, achieved a VGPR [very good partial response].
And she remained on the therapy until 2021, when she again had elevation. At this point, her myeloma completely gave up making heavy chains, just a light chain with new findings on the bone. Interesting enough, since the initial diagnosis, this patient never had diffuse marrow infiltration. Again, every time she does a marrow, which has been on a few clinical trials, or has done a few, it’s a totally clean marrow. You can see this macro-focal pattern of disease.
So, in 2021, now she has triple-class exposed, triple-class refractory myeloma, the patient who is still doing very well. She collects cells for CAR T [chimeric antigen receptor T cells]. It’s something that sometimes we get wrong but knowing the patient for years and feeling the pace of the disease, you can tell who is a good idea to skip bridging who is not. And she seemed like a good idea to skip bridge [therapy]. And she did well without any bridging therapy and received a BCMA [B-cell maturation antigen]-directed CAR T, had really no problems. I think her disease was mean and stubborn but was not big. So she had a few areas of disease, probably didn’t drive a lot of the toxicity.
And she obtained a quick and deep response with a stringent CR [complete response]. So, the patient did well. At this point, she was retired, enjoying [her] grandkids, and loved to not have to come see us very often, didn’t have any problems with infection. But now, 23 months later, this patient has leg pain again, which is a place where her disease tends to come back. And if you look at her PET scan, you see a very clear uptake in the femur, actually bilateral, and it’s small on the pelvis, but a whole lot more. And again, with the elevation of free kappa light chain in the few hundreds range.
So, I think that’s the dilemma we have now. A patient like that, who has now had, if you count, 4 lines of therapy, they included a BCMA-directed therapy, but it has been 23 months, what should we do next?
Transcript is AI-generated and edited for readability.