Managing CRS and Infections Associated With Talquetamab in Myeloma

Naresh Bumma, MD

Assistant Professor

Division of Hematology

Ohio State University Comprehensive Cancer Center

Columbus, OH

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

CASE SUMMARY

• Rich is a 72-year-old man diagnosed 6 years ago with multiple myeloma, 60% plasma cells, translocation 14;20.
• Medical history: respiratory infections (2 episodes of pneumonia, and multiple episodes of bronchitis over prior 10 years)
• Received 5 prior line of therapy, most recently B-cell maturation antigen (BCMA)–directed CAR (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 (Talvey) was initiated via step-up dosing (800 mcg/kg every 2 weeks)

Targeted Oncology^TM: Can you discuss early toxicities seen with talquetamab in relapsed/refractory multiple myeloma in the MonumenTAL-1 trial (NCT03399799)?

Naresh Bumma, MD: The big one everybody talks about is cytokine release syndrome [CRS]. Overall, the CRS rate, looking at grade 1 was 57%, grade 2 was 17%, and grade 3 was 1.5%. [In the first step-up dose, CRS was 29% and 44% for the second step-up dose for both dosing schedules]. In the every-2-week dose arm, there was a third step-up dose. There was a 33% CRS there. In the weekly arm, it was 30% at the first treatment dose. And then after that, it went down to single-digit numbers, but not 0. The [effects] of CRS are in the beginning, so that's something to watch out for.¹

When do you send the patient back to the community setting after step-up dosing?

[I do so] whenever the community is willing to take them back. It depends on the comfort level of the other person too...do you have the support, do you feel comfortable? It's a team sport, so you want to be respectful of your team partner. If your team partner can't handle this right now, we keep them longer. If they [say] send them over, I'm ready, I send them over. For me, it's very much a case-by-case discussion.

There are 3 stakeholders in this discussion. I'm probably the least important, the patient is probably the most important, and then I think my partner in the community is probably the second most important, because different people have different level of resources and support from the institution, and if they're not able to—it could be that your nurse is not comfortable, if you have 2 infusion nurses and both of them are saying no, what are you going to do about it? So I let them decide when they feel comfortable.

CASE UPDATE

• During admission, Rich experiences grade 1 CRS after the second step-up dose.
• He also reports altered taste and dry mouth during step-up dosing.
• By end of first month of treatment, Rich has achieved stringent complete response, but is experiencing:
  • Oral: complete loss of taste and dry mouth
  • Skin: dry skin, skin exfoliation on hands and feet
  • Nails: ridging and peeling

What are the key adverse events (AEs) associated with talquetamab, and what are the rates for the AEs Rich experienced?

CRS incidences were 77% [for all grades], and grade 3 or higher was 1.5%. You can predict when it's going to happen. The time to onset is 26 to 28 hours. Most of them resolve; only 0.3% of patients on this study required discontinuation because of CRS. Median duration was 14.5 to 20.4 hours. ICANS [immune effector cell-associated neurotoxicity syndrome] was less common. Incidents were 7.7% [all grade], grade 3/4, 1.8%. Time of onset was a little bit longer [than CRS], so it can be anywhere between 24 to 115 hours. Most of them resolved, and only 0.9% of patients discontinued because of ICANS. It can last between 7.4 to 48.5 hours, so you can have a longer duration.²

Infections were seen in about two-thirds of patients. About 20% of them had grade 3 or 4. Time of onset was anywhere between 96 to 148 hours, but 89% of infections were resolved. About 1% discontinued because of that, and it can last from 11.5 to 12 days duration. The infections can be significant…. The most common were viral infections, but there were also newer infections. So the usual bacterial, pneumonia, upper respiratory, or pneumocystis jirovecii pneumonia infection. There was also cases of cytomegalovirus and Epstein–Barr virus infection. Not on the talquetamab study, but on other T-cell redirected studies, there have been cases of progressive multifocal leukoencephalopathy with John Cunningham virus activation.

For antiviral [medications], everybody's on prophylaxis of your choice, and then I do very aggressive intravenous immunoglobulin repletion for patients who have hypogammaglobulinemia. If they don't have infection, I do 300 to 400 mg/kg. But sometimes I have patients who have normal IgG [immunoglobulin G] levels, but they still have a lot of recurrent infections. So in those cases, I push for IVIG, even if the IgG level is normal.

What were some other notable AEs in MonumenTAL-1?

Weight decrease occurred in 40% [any grade], and grade 3 or 4 at 3.2%. Median time of onset was 87 to 91 days. It was resolved in about 40%. Only 0.9% discontinued.

The big ones are these oral AEs, dysphagia, dysgeusia, and dry mouth. About 24% of patients had dysphagia [any grade], and less than 1% grade 3 or 4. No one discontinued because of dysphagia. Dysgeusia basically means any case abnormality. One thing I like to point out about this is that they'll say they're all grade 1 or 2. There's no grade 3 or 4 dysgeusia; it doesn't exist. The worst you can get is grade 1 or 2. Only 0.6% of patients discontinued because of dysgeusia. Dysgeusia means any abnormal taste, if they don't taste anything, it tastes bad, it tastes horrible, etc. You have the whole gamut of it. For dry mouth, 36% of patients had any grade]. Grade 3 or 4 was 0%. Nobody discontinued because of that.

Rash occurred in 34.8% [any grade and] 3.5% grade 3 or more. Most of them resolved. Median duration was 15 to 28 days, and nobody stopped because of that. There are some non-rash skin toxicities, like skin sloughing, almost like hand-foot syndrome. Any-grade incidence was about 65.2%, and 0.3% grade 3 or more. Most of them resolved. Only 0.9% of patients discontinued, and median duration was 32 to 39 days.

Overall, how did these toxicities affect dose reductions and discontinuations?

Very few patients stopped treatment because of [AEs]. You can make the argument that they don't want the disease to come back. If you're in a complete response, [they could] stop, but most of the patients did not stop. Dose reductions [due to AEs] were done in 15% in the weekly group, 10% in the every-2-week group, and 12% in the prior T-cell receptor group. Discontinuation due to AEs was 5%, 10%, and 5%, [respectively], so not a whole lot.

DISCLOSURES: Naresh Bumma, MD, previously reported consulting or advisory roles with Janssen and Sanofi.

REFERENCES:

1. Talvey (talquetamab-tgvs) Prescribing Information. Accessed May 21, 2025. https://tinyurl.com/5n6ebc5x

2. Chari A, Krishnan A, Rasche L, et al. Clinical management of patients with relapsed/refractory multiple myeloma treated with talquetamab. Clin Lymphoma Myeloma Leuk. 2024;24(10):665-693.e14. doi:10.1016/j.clml.2024.05.003