Expanding Bispecific Antibody Use in Community Oncology Practice

Jeffrey V. Matous, MD

Bispecific antibodies represent a transformative advancement in multiple myeloma treatment, offering another avenue of targeted therapy for patients with relapsed/refractory disease. Jeffrey V. Matous, MD, clinical professor of medicine at the University of Colorado Health Sciences Center and acting chair of the Myeloma Committee at Sarah Cannon Research Institute at HealthONE in Denver, Colorado, discussed real-world dosing strategies for teclistamab (Tecvayli) at an in-person Case-Based Roundtable meeting in Dallas, Texas. Matous emphasized schedule adjustments to balance efficacy with tolerability and advocated for broader adoption of bispecific antibodies in community oncology.

CASE SUMMARY

• A 74-year-old woman diagnosed 7 years ago with IgG-kappa multiple myeloma, 60% plasma cells, translocation 14;20
• Medical history: chronic kidney disease (stage IIIb), frequent urinary tract infections, anemia
• Received 4 prior lines of therapy; unable to receive B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy.
• She now presented with progressive disease reporting increased fatigue and persistent bone pain (increased free light chains)
• ECOG performance status: 2
• Repeat PET/CT: osteolytic lesions in L4-L5
• Repeat clinical workup at relapse showed:
  • Hemoglobin: 8.8 g/dL
  • White blood cell count: 3.5 x 10⁹/L
  • Platelets: 120 x 10⁹/L
  • Estimated glomerular filtration rate: 40
  • Blood urea nitrogen: 21 mg/dL
  • Creatinine: 2.6 mg/dL
  • Blood urea nitrogen: creatine ratio 8.1 (renal)
• Additional laboratory findings:
  • Fluorescence in situ hybridization: acquired gain/amplification 1q abnormality found
  • β₂-Microglobulin: 6.1 mg/dL
  • BCMA-positive plasma cells: 67%
  • Lactate dehydrogenase: 281 U/L
• She was initiated on teclistamab via step-up dosing at 1.5 mg/kg once-weekly dosing.

Targeted Oncology: What are some concerns you think about for this patient relapsed/refractory multiple myeloma when using teclistamab?

Jeffrey V. Matous, MD: All of us take into account frailty [and knowing] what your patient can handle...as well as logistics and convenience and what patients want to go through. That's the only reason we have ixazomib (Ninlaro) out right now; ixazomib has only lingered on all these years because it's an oral proteasome inhibitor. Otherwise, nobody would give it.

This patient received teclistamab, which is given with 3 step-up doses, where you increase it by 5-fold each dose.¹ That would be 0.06 to 0.3 to 1.5 mg/kg, which is the treatment dose. You do that over a period of several days. It doesn't have to be written in stone how you do this, but you want at least 48 hours to go between step-up doses. What we do in the real world [is not the same as] the FDA label for weekly dosing. After 6 months, if you have a really good response, you can go to every-other-week dosing, but I don't know anybody who does that. When I think about giving teclistamab, I think about a daratumumab [Darzalex] schedule. That's what we do in our practice, very similar to that where get your response, give it weekly, then start spacing your responses out.

We have patients who are on the MajesTEC-1 [NCT03145181; NCT04557098] and MajesTEC-2 [NCT04722146] studies who are now on quarterly dosing of teclistamab. So the [weekly] dosing is from the label, but this isn't what most of us do.

What do you think of physicians referring to academic centers instead of using teclistimab and other bispecific antibodies at their practice?

It's just like if daratumumab came out and someone said, “No, we're not going to use daratumumab. We don't like the intravenous infusion all day.” You have to use daratumumab. Now, daratumumab is being used in smoldering myeloma, the front line and relapsed setting, and as maintenance. The bispecific antibodies are going be the same way.

We've been telling our colleagues they have to get their feet wet with this. We appreciate getting the referrals, but if you're going to be treating your patients with modern therapies, you have to be able to do bispecifics, I think. Also, because bispecifics are going to be given in earlier lines. At the 2024 American Society of Hematology Annual Meeting, there were studies using bispecifics in combination in earlier lines of therapy, frontline to be specific.

What were the data in behind the approval for teclistamab in this myeloma population?

MajesTEC-1 is the trial that got teclistamab FDA approved and was published in The New England Journal of Medicine in 2022.² MajesTEC-1 was a trial that took patients who had at least 3 prior lines of therapy and had to be triple-class exposed to a prior proteasome inhibitor, immunomodulatory drug, and anti-CD38. They could not have had a prior BCMA-targeted therapy, but that would have been just CAR T cell back then. If patients were enrolled, they got to the step-up dose that I explained before, and they got weekly dosing until progression. But we didn't know how to use the bispecifics, and when you did weekly dosing until progression, what we saw was exorbitant adverse events, which resulted in us changing the schedule. Then patients were followed and MajesTEC-1 is still ongoing, asking a lot of different questions.

Disclosures: Matous previously reported serving on advisory committees for BeiGene and Janssen, and serving on a data monitoring board for BeiGene.

_References:

_{1. Tecvayli prescribing information. FDA. Accessed June 26, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf}

_{2. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478}