Comfort With Dose Reduction of Myeloma Bispecific Depends on Response

The bispecific T-cell engager talquetamab (Talvey) has some distinct adverse events (AEs) compared with drugs of the same class that target B-cell maturation antigen (BCMA) in multiple myeloma, with fewer hematological AEs and more oral, skin, and nail toxicity. During a live Case-Based Roundtable event in Minneapolis, Minnesota, Shaji Kumar, MD, professor of medicine and research chair in the division of hematology at the Mayo Clinic in Rochester, Minnesota, discussed a patient case and reviewed the supportive care for these AEs. He also evaluated dose modification strategies, noting that physicians can be more confident in this approach when the disease is clearly responding to treatment.

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

CASE SUMMARY

• A 72-year-old man was diagnosed 6 years ago with multiple myeloma, 60% plasma cells, and translocation 14;20.
• Medical history: respiratory infections (2 episodes of pneumonia and multiple episodes of bronchitis over prior 10 years)
• The patient received 4 prior lines of therapy, most recently BCMA-directed chimeric antigen receptor T-cell infusion.
• He now presented with progressive disease (increased free light chain, creatinine 2.3 mg/dL)
• ECOG performance status: 2
• Talquetamab was initiated via step-up dosing (0.8 mg/kg every 2 weeks).

Targeted Oncology: What are the most notable adverse events with talquetamab?

Shaji Kumar, MD: The main things are kind of unique to the GPRC5D targeted therapy: the skin-nail related toxicity, everything epidermal in nature, and sometimes the oral toxicity can be quite significant.¹ Sometimes you don't realize how much it's affecting the patient. Sometimes you see the patient has dropped 10 to 15 pounds.

What types of high-grade infections were reported in patients receiving talquetamab?

It's a mix of things, bacterial, viral. Fungal [infections] are very uncommon, and [for] the bacterial, most of them tend to be pulmonary or upper respiratory transmissions.

CASE UPDATE

• During admission, he experienced grade 1 cytokine release syndrome (CRS) after the second step-up dose.
• He also reported altered taste and dry mouth during step-up dosing.
• By end of the first month of treatment, the patient achieved stringent complete response (sCR), but is experiencing the following AEs:
• Oral: complete loss of taste and dry mouth
• Skin: dry skin, skin exfoliation on hands and feet
• Nails: ridging and peeling

What supportive care can be given for these toxicities?

For some of the dermatological and skin adverse events, [supportive care includes] moisturizing cream, using some of the nail hardeners; people have been using some vitamin E oil, steroids can be tried as well.² I don't think for any given patient there's something that always works. You have to do a little bit of trial and error to see what helps. With the oral ones, it mostly [needs] some steroids [and] there's nystatin oral rinses.

I think the 1 thing that we should always try in these patients is schedule modification and coming back down on the dose. We feel very comfortable doing this in somebody who is already responding to therapy, [that is if] somebody is already in a complete response after cycle 1 or cycle 2. You can either go down to 0.4 mg/kg every 2 weeks or go down to 0.8 mg/kg every 4 weeks. Either way, there is a schedule or dose in order to reduce the intensity of therapy. In this patient, those measures were taken.

Now, when you look at the infection, which is the second biggest thing with all these bispecifics, the overall infection rates are a little bit less with talquetamab than what we see with the B-cell maturation antigen bispecifics, because the target is a little bit different.The B-cell depletion isn't that profound with the talquetamab. Still, you're seeing a 20% to 30% [rate of] grade 3/4 infections, whereas with the teclistamab [Tecvayli], that was closer to about 50% in those patients, a little bit higher.^3,4 There is zoster reactivation, but you can also get cytomegalovirus [CMV] viremia….

CASE UPDATE

• The patient remains in an sCR on monthly dosing. His taste changes are intermittent and at grade 1 or lower.
• Skin exfoliation resolved during cycle 2.
• Nail changes continue.

What data support reduced dose intensity of talquetamab?

There are not a lot of prospective data in terms of the appropriate or the best way to dose intensify these patients. [The analysis] is from the clinical trial where different patients had different approaches to how they dose de-intensified.⁵ You can either go from 0.8 mg/kg to 0.4 mg/kg for every 2 weeks or stay at the 0.8 mg/kg but go to every 4 weeks. Obviously, when you look at the survival outcomes, it's a little bit hard to interpret, because patients who underwent those dose modifications are often the ones who responded already, so obviously we already know, the people who respond well are going to have better progression-free survival. This analysis doesn't really help much, except to say that we are probably not losing a lot of ground by dose de-intensifying once they get a response.

This shows that with the prospective dose modification, you're not losing much in terms of the efficacy of the drug [Table⁵]. I think that's a key message with most of these. But at the same time, you're able to modify or decrease the toxicity with dose.

I don't think we'll ever have a prospective trial, but I think we'll get a lot of data from all these large databases like the [Cancer] Immunotherapy Consortium with the real-world data that hopefully will give us a better sense of what is the right dose. But the bottom line is, I think once people are in a deep response, we certainly don't need to maintain the dose intensity. We can certainly back off. It’s partly driven by the response and partly driven by the toxicities.

Is dose de-escalation an option for patients at risk of repeated infection?

The skin and the oral [toxicity] is probably what is mostly driving the dose modifications; the infection is not quite as much. I think if you [give prophylaxis] and intravenous immunoglobulin, certainly it reduces the risk of infections. Generally, what I've been doing is, if somebody gets one infection, maybe not quite trigger the dose modification right away. If they get skin toxicity [that is] very mild, and it responds to the supportive care measures, maybe not reduce the intensity. But if it's severe, then we definitely hold the drug and start at lower intensity afterwards. If they get repeated infections, [do] the same thing, back off on that. Again, how fast you back off depends on—if somebody's in complete response, I feel more comfortable backing off and compared with somebody who is only in a partial response, for example.

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_{DISCLOSURES:Kumar previously reported receiving research support from AbbVie, Adaptive, Celgene, Johnson & Johnson, KITE, MedImmune/Astra Zeneca, and Takeda, and has been an advisory committee member for AbbVie, Adaptive, Celgene Johnson & Johnson, KITE, MedImmune/Astra Zeneca, Merck, Novartis, Oncopeptides, Roche, Sanofi, and Takeda}

REFERENCES

1. Rasche L, Schinke C, Touzeau C, et al. Efficacy and safety from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: Analyses at an extended median follow-up. J Clin Oncol. 2025;43(suppl 16):7528. doi:10.1200/JCO.2025.43.16_suppl.7528

2. Talvey. Prescribing information. Janssen Pharmaceutical Companies; 2023. Accessed March 16, 2026. https://tinyurl.com/ym3jfs6f 

3. Schinke C, Rodriguez-Otero P, van de Donk NWCJ, et al. Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1. Blood Adv. 2025;9(22):5752-5762. doi:10.1182/bloodadvances.2025016613

4. Nooka AK, Rodriguez C, Mateos MV, et al. Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study. Cancer. 2024;130(6):886-900. doi:10.1002/cncr.35107

5. 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