Improving Management of Relapsed/Refractory Multiple Myeloma - Episode 10

Targeted Treatment Options in Multiple Myeloma


Thomas Martin, MD: Is there anything else that has your interest in the relapse setting?

Yvonne Efebera, MD:The toxicities of isatuximab (ISA) were really manageable. I agree with the NCCN (National Comprehensive Cancer Network) guideline, so we put isatuximab as category 1 because it was a larger study, well conducted, and did not have much toxicity either, apart from the pulmonary. No prophylactic regimen was given on that study. I know they had about 20% to 28% of pneumonia and bronchitis and upper respiratory infection. Do you give prophylactic treatment? That’s something that could be considered when we give patients this treatment. Otherwise, it was well tolerated.

The other drug, you know, targeted therapy, is chimeric antigen receptor T cells (CAR T). That’s the area of great research and discussion. In terms of relapse, I think that’s where we are heading to. Yesterday, the FDA gave unanimous approval to proceed for discussion regarding FDA approval for the antibody-drug conjugate (ADC), belantamab, as a single agent. That’s great.

The study that was published was a single agent, but the DREAMM-2 study looked at belantamab with bortezomib/dexamethasone, or belantamab with lenalidomide/dexamethasone. At ASCO (American Society of Clinical Oncology annual meeting), belantamab/Velcade/DEX (dexamethasone) was presented with 59 patients. On that, the overall response rate was 78% with a very good partial response (VGPR) of more than 50%. Clinical benefit—when you’ve had multiple relapses, you always look at stable or minimal response (MR) clinical benefit—was 83% for the dose of 2.5 mg/kg. It’s well tolerated and given every 3 weeks. The eye problems we saw in the DREAMM-2 study are not a big issue at all. It’s manageable by them seeing an ophthalmologist first or during, and some patients just use eye drops. I’m excited about belantamab.

Of course, the CARTITUDE and karMMa studies showed a 97% response or higher. The cytopenias in that were very high, 97%, so we are really scratching the surface of the CAR T. In CARTITUDE … to gratitude, right, patients who are having 3 or more prior lines. These are patients who have had up to 18 prior lines of therapy seeing some clinical benefit in those studies. The quality of life was also assessed, which was better with the studies.

Last, but not least, was the bispecifics antibody, teclistamab, that was also presented at ASCO. There were 66 patients, and it showed up to a 78% response at the highest dose of 270 mcg/kg. The cytokine release syndrome and newer toxicities are usually things that need to be discussed and managed with the patient. I’m curious to hear your thoughts about these new drugs.

Thomas Martin, MD: You beautifully described those 3 classes, the ADC the CARs, and the bispecifics that are now targeting B-cell maturation antigens (BCMA). There are going to be other targets and similar types of novel immunotherapies. We haven’t had a big problem with the ocular toxicity with belantamab mafodotin. We have a good relationship with our ophthalmologist. It hasn’t been problematic in terms of dosing. I’m very curious because they have a randomized trial where they are going to go head-to-head against a variety of different agents, including daratumumab (DARA)—belantamab/bortezomib (VEL)/DEX versus DARA/VEL/DEX. It will be interesting to see that. Then there’s lenalidomide, bortezomib, and dexamethasone (RVd) versus belantamab/RVd. I’m curious to see the results of that one, too. I do think we’ll have to figure out the dosing.

In terms of the CARs, we’re all excited, but at the end of the day, it’s not lymphoma where the CARs last for a tremendously long time, maybe forever.

Yvonne Efebera, MD: I agree.

Thomas Martin, MD: At some point, in myeloma, it seems like everybody is going to relapse, so I think the take-home point, in terms of the CARs for me, is that it’s not going to be; we’re hoping for a one-time dose of CARs, and then they don’t need any therapy. We have to figure out what maintenance to give afterwards, and also, if and when they relapse, what to give them as salvage therapy. I gave the review of teclistamab at ASCO virtual, and I was really impressed by the data. We have 3 bispecific T-cell engagers that have shown more than 50% for response rates. We have AMG 420, we have the BMS (Bristol Myers Squibb) CC-93269, and then we have teclistamab.

With the BMS therapeutic, and also with teclistamab, some of these patients are out more than a year in continuous remission, and they’re looking durable and continue to get therapy. There’s a little bit less cytokine release syndrome (CRS) with CARs; 80% or more have CRS, with a bi at 50% to 60% and less neurotoxicity. It could be that a monthly dose of a bispecific might be the best therapeutic out there. Single agent, no steroid… For me it’s amazing, and then at the end of the day, can’t we all get along? Maybe we use them all together. Maybe they get an ADC as front-line therapy and then a CAR as consolidation instead of a transplant, with a bi as maintenance after that.

Yvonne Efebera, MD: In fact, 1 of the things that the BMT CTN (Blood and Marrow Transplant Clinical Trials Network) is looking at is how do we incorporate CAR T? Just like in the lymphomas, there was a randomized trial looking at CAR T versus autologous transplant. That study was completed, and we’ll see what the results are. Can we incorporate CAR T in high risk as a consolidation after autologous transplant, or a patient post-autologous on maintenance and haven’t reached either partial response (PR) or less? Can they benefit from an addition of CAR T? It will be interesting to see. My only thing with the CAR T, even with the lymphoma, is the cytopenias. These patients can have cytopenias for up to 6 months and need transfusion. Again, it’s still early in the game. I’m sure they will be making changes in the constructs and making them better, less cytotoxic. It’s exciting that we have so many avenues and different things to look at for myeloma patients, improving their survival.

Transcript edited for clarity.