Differentiating Bispecific Administration Between Institutions for Multiple Myeloma

A panel of experts discussed their institutions’ practices for administering
bispecific antibodies, BCMA or GPRC5D, to patients with multiple myeloma.

During a Satellite Sessions program that was hosted by CancerNetwork®, a panel of experts in hematologic cancers discussed their institutions’ practices for administering bispecific antibodies, specifically B-cell maturation antigen (BCMA) or GPRC5D, to patients with multiple myeloma. Factors such as chimeric antigen receptor (CAR) T-cell eligibility, distance, age, and agent availability were all considered relevant and worthy of consideration when assessing potential treatment options.

The panel was led by Thomas G. Martin, MD, associate director of the myeloma program at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, director of the Unrelated Donor Transplantation Programs for Adults at UCSF, and research director of hematologic malignancies. He was joined by Alfred Chung, MD, a hematologist-oncologist at UCSF; Katrina Anne Fischer, MD, MBA, an oncologist at Pacific Cancer Care in Monterey, California; Robert W. Weber, MD, a medical oncologist at Sutter Health in San Francisco, California; Samantha Shenoy, MSN, NP, a nurse practitioner at UCSF; Aditi Choudhry, MD, a medical oncologist at John Muir Health in Walnut Creek, California; Gigi Chen, MD, a hematologist at John Muir Health in Walnut Creek, California; Derek A. Wong, MD, an associate clinical professor and medical director of the MS in Genetic Counseling Program, Pediatrics, at UCLA David Geffen School of Medicine; and Ram K. Chillar, MD, a hematologist-oncologist in California.

Candidates for Bispecific Antibodies

Martin / Who are the candidates we should be [administering bispecifics in an outpatient setting]?

Chung / It depends on [whether] they’re eligible for CAR T because there are data that were presented here that [show], after a prior T-cell redirection therapy, the duration of responses is much shorter. If a patient is CAR T–eligible and we have a plan for that, I would do that first. If they’re not going to be eligible for social reasons or health reasons, a lot of patients can tolerate the bispecific antibodies. The cytokine release syndrome [CRS] is generally manageable. Then, as long as we’re careful with the intravenous immunoglobulin prophylaxis and infection monitoring, BCMA bispecifics can be done. With talquetamab-tgvs [Talvey], the toxicity profile is different… I usually go for BCMA first for targeting and then GPRC5D. That’s my practice.

Martin / How about [you], Katrina? Are there patients [who] you refer to [UCSF] and say, “That guy is going to need a bispecific” or somebody [who] you don’t refer, and say, “I’m not going to send that guy [to UCSF]?”

Fischer / We comanage a lot of our patients with multiple myeloma because they’ve seen you [at UCSF and are] ready for transplant, and they’ve been doing maintenance therapy for us. I did recently have somebody on the [GPRC5D], and I referred him up for CAR T. This wasn’t on my radar too much because we’re not giving it, and we haven’t given any bispecific antibodies in Monterey other than with this one patient. It was a big deal to get it all started in our clinic, and our hospital is not willing to do the ramp-up [dosing]. [Jeffrey L. Wolf, MD] had said—the patient’s [older]—and he said, “Let’s do the GPRC5D first because if I want to do [something] BCMA targeted later, I haven’t targeted that yet.”

Weber / No, I refer everybody [to UCSF], and we’re so close that they don’t stay [inpatient].

Choosing the Right Bispecific Antibody

Martin / Sam, do you use BCMA or GPRC5D first?

Shenoy / Like Alfred said, if you can do ciltacabtagene autoleucel [Carvykti], you should do that first, but if you can’t do CAR T, I don’t think it matters if you do BCMA vs GPRC5D first. If you’re talking about bispecific to bispecific, and we’ve done that before, [I prefer] GPRC5D first and then BCMA. I don’t feel like it matters.

Martin / How about you, Gigi and Aditi? What’s your choice at John Muir?

Choudhry / We have both bispecifics available. I don’t have a lot of experience [with them]. I have one patient on teclistamab-cqyv [Tecvayli] right now, but that was [started] before talquetamab got approved. He’s been on it for amyloidosis for the past 3 years now in a complete response.

Now, if I have a patient, I’d probably use talquetamab because it’s GPRC5D. If they need CAR T later, then [I would administer it] because I don’t want to give them a BCMA-directed bispecific. I just haven’t had a patient. One of my partners has—it was 3 weeks ago—I was there for the ramp-up dose. It went just fine, but he’s not my patient, so I don’t know how he’s doing. We can give both.

Chen / We usually first refer to [UCSF] for a CAR T evaluation to see if they’re a CAR T candidate. A lot of it is a discussion to decide on which [bispecific] to go with—the BCMA vs the GPRC5D. Recently, I was on service last week, and we started somebody with talquetamab. That was quite an exciting ramp-up.... We do it on day 1 and day 4, and it sounds like [at UCSF you] do it on day 1 and day 3. [That’s a] faster ramp-up than what we did. There was CRS, and there was a concern for [immune effector cell–associated neurotoxicity syndrome (ICANS)], but I think it was all manageable. I don’t think anybody who rolls in can get it. At least for the ICANS, you have to have them be able to write things and see their handwriting. You have to be able to go through all those tests.

Martin / That’s a good point. Some of our patients didn’t do so well on the ICANS before they got the [medicine]. Derek, how about your practice?

Wong /I refer them all to you.... The first question is, do they get the CAR T? Mainly, we have not done it yet because our hospital is [El Camino Health], and it’s not part of [Sutter Health]. We can’t get it, so it’s been hard to start.

Considering Age When Administering Bispecifics

Martin / For older patients [who] you look at and say, “OK, that guy can’t get a CAR [T-cell therapy],” what do you think about a bispecific [antibody]? Are you thinking that [with] bispecific antibodies, we can accept [patients who are] a little bit less fit?

Wong / I’m looking for the right opportunity to start. Sooner or later, we’re going to have to start giving [bispecific antibodies to them].

Weber / My patient population is very old, and I never thought of it as something they would be eligible for. I thought, “How will they live long enough to get through 4 lines?”

Martin / Well, that is the attrition of multiple myeloma, which is the craziest thing. So, 100% of patients can get line 1 [of treatment], in general. Then, when you get to line 2, we’re down to 60% of patients—the [other] 40% either have died, gotten some bad toxicity, or just quit. You lose that many. [In the] third line of therapy, you lose another 20%, and [in the] fourth line of therapy, you lose another 20%. That’s why we’re trying to move [bispecific antibodies further].

Weber / By that time, you have a battle-tested patient.

Martin / Correct. If they can make [it through] that many lines [of therapy], they can get [bispecific antibodies].

Chen / Is there an age cutoff for CAR T? Anytime I want to give a bispecific antibody, the patient gets taken for CAR T.

Martin / For CAR T, there is not an age cutoff. Over age 85, it starts to get challenging… Under 80, [there is] no problem. Over 80, [it’s] tough. They have to want it.

Discussing Sequencing and Safety

Wong / With the quadruplet therapy [option] now in the first line, and I know it’s relatively new, it’s hard to get to the fourth line. What do you use in the second and third lines when you’ve used all triple-class [therapies]?

Martin / The real answer to your question is based on [the phase 2 GRIFFIN trial (NCT02874742)] because GRIFFIN started way before all this stuff. GRIFFIN was the first [quadruplet therapy] that we used. I think [at UCSF] we put 9 or 10 patients on GRIFFIN. They’re all still in remission. That was [around] 7 years ago.

[The question is], what are we going to use when they come out of remission? The majority of those patients, they’re off treatment. I’ve taken them off as of years 3, 4, or 5, and they’ve been off therapy for 2 or 3 years. Honestly, when they relapse, anything’s possible. Whatever’s available at that point in time, to tell you the truth, because they’re not going to be refractory to anything.... We’re going to be able to use whatever the best thing is at that point in time.

Chillar / Likewise, I have these patients from the Bay Area who are shifting to the Carson Valley [location], and sometimes it becomes an issue. Most of them are in [their] 80s. I’m strictly advising them that it is available there. The one we tried [this] with, this gentleman is 93 [years old] already. He says, “What are my options now? I’ve run out of everything.” I said, “This is a possibility, but you may not have the ability to withstand some of the [adverse] effects. [You] might be done with the CRS, even though we are getting better at handling it.” I’m troubled in that narrow channel.

Martin / In the real world, we have all these toxicities: skin, nails, and dysgeusia. Sam, how do we manage those?

Shenoy / The biggest thing…is setting expectations from the very beginning. Giving [the patient] a handout [helps]; it gives them tips about how to manage the [adverse] effects. [It’s] so important to give patients those tools so they go in feeling like they can do something about some of the [adverse] effects that they’re going to experience.

For dysgeusia, which is the most bothersome symptom, dose reduction, which once they’ve achieved a [partial response], usually by cycle 3 or 4, it’s safe to go from dosing every 2 weeks to monthly. That is probably one of the best things you can do.... Honestly, the best thing you can do is dose reduction when they’ve achieved a partial response. After that, just [give them] the best supportive care that you can.

Reference

Voorhees PM, Sborov DW, Laubach J, et al. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol. 2023;10(10):e825-e837. doi:10.1016/S2352-3026(23)00217-X