Managing Dose Reductions With Bispecific Therapies in Myeloma

Dose modification is a critical consideration in multiple myeloma treatment, as adjusting therapy intensity can help balance efficacy with tolerability for patients. An in-person Case-Based Roundtable meeting in Philadelphia, Pennsylvania led by Alfred L. Garfall, MD, director of autologous hematopoietic stem cell transplantation, section chief of myeloma, hematology-oncology, and associate professor of medicine (hematology-oncology) at the Hospital of the University of Pennsylvania, touched on the subject of dose modification for talquetamab (Talvey). He highlighted findings from the MonumenTAL-1 study (NCT03399799)and shared insights on long-term dosing strategies.

This article is part 2 of a 2-part series from a Case-Based Roundtable event.

Targeted Oncology: What was the result of the analysis done for the MonumenTAL-1 dose modification?

Alfred L. Garfall, MD: For a good portion of the study, patients did dose reduction in response to adverse events. Then there was another smaller portion of the study where there was prospective dose reduction with lower-intensity doses. The dose reductions occurred at a median of 3.2 months after starting the drugs.¹ I always find these data a little bit confusing to get through. [Among] patients in the weekly, biweekly, and the prior T-cell redirection cohorts, responders with dose reduction still had very impressive median duration of response. It was 19.8 months into the weekly group, [not estimable in the biweekly group], and 24.2 months in the primary T-cell redirection [group], so [there was] no sense that dose reduction was leading to unacceptable duration of response. These are still very clinically meaningful durations of response for this population. Along the same lines, the patients after dose reduction still maintain their response in the vast majority of cases.

What is your usual dosing schedule long term for talquetamab?

We basically get everybody down to every-4-week dosing after a couple months. Once it's clear they're responding—responses happen quickly, they're deep initially—and then we get them down to every-4-week dosing. Almost everybody has some reason for that. At that point, what you're trying to do is find a strategy to keep the patients on the drug as long as possible if they're responding.

If the patient is losing response, do you increase the dose?

I don't think so. We've done much more of that with teclistamab [Tecvayli] than talquetamab, and we've never really had a patient respond to re-intensification. We've had patients respond to it who were off it for a very long time. A couple patients were off for maybe 18 months, they had progression, and they were re-initiated [later]. You can make the case that a lot of the dosing here is over-dosing the antibody therapies that would go away in a month. So stretching the dosing out to every 2 months, if they have progression through every-4- or every-2-week dosing, I don't think re-intensifying—I've never seen that help.

Have you used an anti-CD38 antibody as combination therapy with a bispecific therapy in this multiple myeloma population?

That's definitely off label. I have never combined these drugs with other drugs. I have some colleagues, and there definitely would be a reimbursement problem, like adding in an infusion medication. I have had some colleagues who have added in pomalidomide [Pomalyst] with the bispecific antibody in a patient who's progressing, and those combinations have been studied; at least they're reasonably safe, and they've seen some responses, but to be honest with you, they might be responses to the immunomodulatory drug. A lot of these patients have been on these drugs for so long that when they're progressing, it's been many months or years since they have seen any of the conventional myeloma agents. They may just respond to those agents at that point because it's been a while since they got them.

When you restart a patient after a treatment break, do you use step-up dosing again, or you put them on the maintenance dose they were on?

It depends on the length of the break. There's guidance in the label for these drugs for this.² I know more for teclistamab than talquetamab, but within a few months, you can go back and continue the dosing you were on. But beyond that, you should [use step-up dosing]. What I would encourage folks to do in practice with teclistamab is look at the European Medicines Agency label, which has adopted a more evidence-based, recently-developed set of data based on the duration since the last dose.³ For many patients who can get by with either just continuing the same dose or repeating the second step-up dose. For someone who has been off for a long time, you have to go back to the first step-up dose. The European Medicines Agency guidance gives you specific guidelines. The FDA adopted it, and we adopted into our center.

DISCLOSURES: Garfall previously disclosed research funding (to institution) from Novartis, Johnson & Johnson, CRISPR Therapeutics, Tmunity, Consulting fees from Johnson & Johnson, Regeneron, BMS, Abbvie, Smart Immune, Novartis and IDMC/DSMB membership at Johnson & Johnson.

REFERENCES:

1. Chari A, Oriol A, Krishnan A, et al. Efficacy and safety of less frequent/lower intensity dosing of talquetamab in patients with relapsed/refractory multiple myeloma: results from the phase 1/2 MonumenTAL-1 study. Blood. 2023;142(suppl 1):1010. doi:10.1182/blood-2023-181228

2. Talvey prescribing information. FDA. Accessed July 8, 2025. chrome- https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf

3. Tecvayli. European Medicines Agency. Accessed July 8, 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/tecvayli