Introduction: Overview of Bispecific Antibody Therapy in Late-Line Multiple Myeloma

Watch Round 1 Here!

Beth Faiman: Hello, everyone. Welcome to our lunchtime symposium. The topic is optimizing bispecific antibody therapy in late-line multiple myeloma, expanding clinical use versus addressing toxicity concerns. Please enjoy your lovely meal. I hope it meets your meet your minimum requirement for a lunch in New York on a Saturday. I am joined today by esteemed colleagues, Donna Catamero, who you saw before, and Charise Gleason, who flew in from Emory Winship in Atlanta to be with us today. Thank you, Charise, for joining us. We want to make sure that you share your perspective. So we have the debate-style program here; so, here's the QR code. You can't get a free steak for lunch without participating in our polls. Another one? No, you can have mine. I'm a vegetarian. So please scan the QR code, and you can participate in a pre-debate poll. And I think there are a few, just a few polls later on. So again, I'm Beth Faiman. Oh, go back, back, back. I'm going to leave it on for another minute.

Look at all these people taking out their phones. That's awesome. Do you know, I go to these meetings and I don't want to say half the time I'm like, oh, other people will do it. I don't need to do it. I've been much better. Yeah, I might skew the results if I join in. We good? Good, good, good. Alright, I'm going to move on. There's me, I just have a few short slides to set the stage. And again, we're going to be talking pro, con, inpatient, and outpatient management of myeloma. When we're considering types of therapies for patients with relapsed myeloma, it's not different than leukemia or lymphoma or many of our other blood hematologic conditions. You're considering various factors such as the patient, the disease, and the treatment regimen. I love Jenny Goebbels' slide this morning about how it was like age, less than 60, over 60; we don't do that anymore. Fitness, we don't do that anymore. 

I think that this has evolved in the last few years. We consider their performance status. Patient preference is huge in all of our cancers, including myeloma and their comorbid conditions, because the concurrent medications can influence what the doses of the drugs we prescribe are, et cetera. The disease burden, if you have a rapidly progressive disease versus a slow increase in their monoclonal proteins, that's different. Then, the biology of the disease. We heard earlier this morning from Dr Williams about the next-generation sequencing, cytogenetics, and the importance of personalizing care in hematologic cancers, and cytogenetics, translocations, and deletions are all important in myeloma. Then we also consider the treatment. What is the risk of myelosuppression infections? Do they have preexisting neuropathy? Will we give them worsening neuropathy? And what is the overall risk of second cancers, or do they have a second cancer?

If so, they wouldn't be able to, in many cases, participate in a well-designed clinical trial because that secondary cancer would eliminate them or exclude them based on most of the schemas. The access in cost of care in standard therapy, relapsed/refractory, and then of course the regimen. In newly diagnosed myeloma, we use four drugs: the anti-CD38 monoclonal antibody, usually bortezomib, lenalidomide, and dexamethasone. Then, in relapse disease, it's a triplet that's generally preferred over doublet therapy. We have numerous different therapies available. We like to include one or more agents from another drug class as well. Then, we treat to maximum response; so, FDA approved in myeloma patients after three prior lines of therapy. So, their fourth line of therapy is bispecific antibodies. Bispecific antibodies were specifically designed to be given in the community where patients reside, but there are so many different factors to consider.

I know you probably can't see this small font, and that's okay. I'm just going to hit the key highlights here. When we're thinking about the different considerations of starting an outpatient bispecific program, we have to first have some experience in giving these drugs before we move them to an outpatient setting. These have severe toxicity, such as cytokine release syndrome, neurotoxicity, or ICANS, as well as infections. Patients, if they get it in the outpatient setting, will have to have access to an emergency setting or an ICU. What if you have one of those severe effects? How are you going to be managed? Then, all relevant health care providers need to be trained on a new process of giving these drugs outpatient, from the ER, to the outpatient, and to the inpatient setting. Patients need to be eligible to receive these drugs as an outpatient with a performance status, and make sure they don't have any high tumor burden.

Again, this is applicable to lymphoma and myeloma bispecifics as well. The treatment initiation is usually their step-up dosing, depending on the agent. In myeloma, we have teclistamab, elranatamab, and linvoseltamab, which are the BCA-directed bispecific antibodies, and talquetamab is GPRC5D. Premedication is super important. Then, post step-up dosing, you're going to monitor them for late effects of these drugs. Infection is specifically—and we'll go into more details— and, then again, adverse management. There are guidelines that exist for our patients, but they need to be monitored at least 48 hours after each step-up dose, inpatient or outpatient. So, how do we operationalize that? That's what we'll be discussing today. This is just a slide that highlights the different step-up dosing administration schedule for teclistamab, talquetamab, elranatamab, and linvoseltamab, the four FDA-approved agents.

Do you say after three prior lines or four prior lines? I think it's in fourth line. So everybody has it different. They have to have had three prior lines of therapy. The fourth line of therapy, just to be consistent and be on the same page. The verbiage changes, but in the fifth line, after four prior lines—I did say that, why did I fall asleep for a minute? It's been a long morning. Beth, know the indication. I do this for a living, by the way, too, but sometimes I forget. So teclistamab, talquetamab, elranatamab, and linvoseltamab all have different onset of CRS, so you can all give them various differencing, but this is an example of an inpatient dosing schedule. So days 1, 3, and 5, for example, are for the teclistamab. So, that means that after their premedication, you have to monitor them for 48 hours after that step-up dose number five.

They're in the hospital for like 7 days; same with talquetamab. In many institutions, if they're inpatient hospitalized. Elranatamab, based on the CRS, some protocols after days 1 and 3, you can discharge with a certain protocol to monitor for CRS. Then, linvoseltamab is totally different. This is IV; the other three are SubQ, and the worry is that at 11 hours, you can get your CRS. So, on day 1, you could theoretically give it outpatient, monitor for 23 hours, and discharge. Then come back on day 8, monitor for 23 hours, and then discharge. Then, day 15 is their step-up dose. So again, four different bispecific antibodies, four different types, timeframes with the CRS, ICANS, neurotoxicity, but infection remains. Grading is here very briefly. We're going to have a CAR T talk later on, and go into great detail as well. But you can't have a cytokine release syndrome.

Jenny had that cute little slide of how the cytokines are released with the bispecific in her leukemia talk. Grade one is fever; you can't have CRS without a fever, and then it escalates 2, 3, 4 as well. Then, for neurotoxicity, we do the ICE score, the Immune Effector Cell-Associated Scoring System; 10 is no impairment, 0 is unarousable, like they're a vegetable. Hopefully, you're going to get them before they're a 0. But it's a combination of things, such as handwriting, counting backwards from ten for a hundred, looking for seizure, motor findings, et cetera, for that neurotoxicity.