Recent Advances in the Treatment of Relapsed/Refractory Multiple Myeloma - Episode 1
Expert hematologist/oncologists review the case of a 69-year-old man with multiple myeloma who had a biochemical relapse and share their approaches to treatment.
Nina Shah, MD: Hello, and welcome to this OncLive® Peer Exchange® titled “Recent Advances in the Treatment of Relapsed/Refractory Multiple Myeloma.” My name is Nina Shah, and I’m a professor of clinical medicine at the University of California San Francisco. I’m joined by a panel of experts in multiple myeloma, all of whom are wonderful doctors and people, and I’d like to welcome my esteemed fellow panelists and ask them to introduce themselves. I’ll start with Dr Katja Weisel.
Katja Weisel, MD: Hi, my name is Katja Weisel. I’m the deputy director of the hematology and oncology and bone marrow transplant department at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.
Nina Shah, MD: Great. Ola?
Ola Landgren, MD, PhD: Hi, I’m Ola Landgren. I’m a professor of medicine and the chief of the myeloma program and the experimental therapeutics program at Sylvester Comprehensive Cancer Center at University of Miami in Florida. Thank you for having me.
Nina Shah, MD: Great. Sagar?
Sagar Lonial, MD, FACP: I’m Sagar Lonial, the chair of hematology and oncology in the department of hematology and medical oncology at Winship Cancer Institute of Emory University in Atlanta, Georgia.
Nina Shah, MD: And Joshua.
Joshua Richter, MD: I’m Josh Richter, an associate professor of medicine at Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and the director of the myeloma program at the Blavatnik Chelsea–Family Medical Center at Mount Sinai in lovely New York, New York. Thank you for having me.
Nina Shah, MD: Great. It’s great to see all you guys. I’m happy we’re able to do part of ASH [American Society of Hematology Annual Meeting] in person. Welcome, and thank you for joining me. We’re going to discuss a number of recent updates in the treatment of multiple myeloma that were presented at key conferences over this past year. We’re going to take the discussion and talk about the data in the context of guidelines, the treatment landscape, and its effect on clinical practice.
Let’s get started on our first topic, which is improving outcomes in multiple myeloma at first relapse. We’re going to start with a case. This is a 69-year-old man who was diagnosed with multiple myeloma in October 2016. At that time, he had lambda subtype multiple myeloma and presented with ISS [International Staging System] stage III disease, but it was a Revised–ISS stage II. His serum free light chain of lambda was 9587 mg/L, and he had 9% plasma cells in the peripheral blood. His cytogenetics showed an addition of 1q and translocation of 11;14. The PET [positron emission tomography] CT had no extramedullary disease, but he did have some positive uptake in the ribs and a collapse of T7. His past medical history is notable for diabetes and hypertension. He’s a retired teacher, generally an active guy, and he loves walking and gardening.
Starting in October 2016, he received VRd [bortezomib, lenalidomide, dexamethasone] for 6 cycles and achieved a stringent CR [complete response]. He went on to consolidation therapy with high-dose chemotherapy with melphalan 200 mg/m2 and autologous stem cell transplant, and then went on to maintenance therapy with lenalidomide starting in October 2017. He generally tolerated this well, but he did have residual grade 2 peripheral neuropathy from prior VRd [bortezomib, lenalidomide, dexamethasone].
In January 2020, in a follow-up visit, his immunofixation tested positive, and then the lambda free light chains started to increase even though he was asymptomatic. At that time, he was considered to have a biochemical relapse and was started on treatment to avoid a clinical relapse. His physician decided to start him on daratumumab-carfilzomib-dexamethasone, also known as dara-Kd, with the carfilzomib at a dose of 70 mg/m2 weekly. At the time, the patient was doing well, with an ECOG performance status of 2. He visits the clinic weekly, has tolerated the treatment, and is active.
This brings up some points for discussion. This is a patient who’s doing pretty well and had a biochemical progression in a few years on lenalidomide maintenance therapy. Let’s go around the room. How would you have treated this person in your practice? I’m going to start with Josh.
Joshua Richter, MD: There’s a lot of debate in early relapse. We have a lot of options. For people who haven’t received a CD38 antibody up front, first relapse is the time to bring it in. The data have recently shown that CD38 Kyprolis regimens appear to be better than CD38 IMiD [immunomodulatory imide drug]. That being said, the wonderful thing about a CD38 IMiD is that at some point you’re getting a once-a-month subcutaneous shot and you remain on pills. I would have had a discussion with the patient about DKd [daratumumab, carfilzomib, dexamethasone], but daratumumab-pomalidomide-dexamethasone is also a great regimen that’s tolerated well, with some pretty good data from the APOLLO and AQUILA studies.
Nina Shah, MD: Yes, that’s a very common opinion. Ola, what about you? How would you have treated this patient?
Ola Landgren, MD, PhD: Josh covered all the important points. Kyprolis-daratumumab works really well, has deep responses, and seems to be very durable. It gives the patients a break from IMiD therapy. The downside is that once you’re a little further out, as Josh already pointed out, the long-term feasibility with an infusional and an injectable drug isn’t as attractive as a pill and an injectable. I have the same conversation with my patients. I ask, “What do you prefer?” If you pick carfilzomib-daratumumab, it’s unfortunately going to stop working at some point, and then you’re going to be back on an IMiD again. Or if you pick the IMiD track now, you may go to this approach.
One little thing I also want to bring up is, in your case, you use weekly 70 mg/m2. That isn’t how the CANDOR trial was done. But that’s along the same lines as the feasibility, to use the drug once a week with carfilzomib instead of twice a week. That’s what I always do. I use it once a week at 56 mg/m2. We probably do these things a little differently, but let’s see what the others think.
Nina Shah, MD: Sagar, what would you have done in this case?
Sagar Lonial, MD, FACP: I take issue with Josh’s presumption that the PI [proteasome inhibitor] CD38 is the optimal approach. They’re both similar. The reason that IMiDs look like they have a shorter PFS [progression-free survival] is it’s at least 1 line later in those randomized trials than the carfilzomib trial. Ola’s point about once-a-week dosing 56 mg/m2 is what most people do, but that’s half the dose of carfilzomib. Are you going to get CANDOR-like outcomes if you use it once a week at 56 mg/m2? That’s equivalent to 20/27 mg/m2, and we all know 20/27 mg/m2 is pretty low-dose carfilzomib. Those are caveats.
One different wrinkle I bring up that hasn’t been brought up so far is that this is an 11;14 patient. To me, this is the optimal time to use venetoclax. I agree with Josh that daratumumab should be part of this salvage. There’s a great trial of venetoclax, daratumumab, and dexamethasone vs bortezomib with daratumumab and dexamethasone. That’s the trial we’d put him on. But earlier use of venetoclax would be what we favor.
Nina Shah, MD: I’m glad you brought up that point, because that’s a subtle detail that might have been forgotten when you get down to 4 years of having this malignancy. Katja, what about you?
Katja Weisel, MD: I fully agree. However, I have to bring a bit of European perspective on that. I wouldn’t have any chance to use venetoclax, although I’d love to have it. Daratumumab-pomalidomide-dexamethasone was recently approved for us to give from second line on. Previously, we had to have 1 line in between. I’m sure most of my colleagues would have also chosen the anti-CD38 carfilzomib approach. However, we also already have the second anti-CD38 antibody approved, isatuximab, in the same regimen, isa-Kd [isatuximab, carfilzomib, dexamethasone], so we don’t know which we should give. There’s no evidence for giving 1 first or the other or doing a switch. To make the picture complete, I wanted to add that point up.
Nina Shah, MD: That’s a really good point: it’s not just daratumumab available as a CD38 antibody but also isatuximab in combination with carfilzomib.
Transcript Edited for Clarity