Teclistamab Combos Are Encouraging in Frontline Myeloma

Findings from an updated analysis of the phase 2 MajesTEC-5 study (NCT05695508),¹ which is evaluating an investigational regimen of teclistamab-cqyv (Tecvayli) combined with daratumumab and hyaluronidase-fihj (Darzalex Faspro) for transplant-eligible patients with newly diagnosed multiple myeloma, demonstrated the regimen's profound clinical efficacy in this frontline setting.

After induction therapy, 100% of patients achieved an overall response, and importantly, 100% of evaluable patients achieved minimal residual disease (MRD) negativity. This suggests a deep and meaningful reduction in cancer cells.²

The treatment also demonstrated a manageable safety profile. Although cytokine release syndrome was observed in 65% of patients, all cases were grade 1 or 2. Notably, no patients experienced immune effector cell–associated neurotoxicity syndrome. The combination's success in achieving deep responses early in the treatment journey, along with its tolerability, underscores its potential as a highly effective, immune-based, steroid-sparing option for newly diagnosed patients.

In an interview with Targeted Oncology, Marc Raab, MD, professor of medicine and clinical director of the Heidelberg Myeloma Center Department of Medicine V, Heidelberg University Hospital in Germany, discussed these findings, which were presented at the 2025 International Myeloma Society (IMS) Annual Meeting.

Targeted Oncology: What is some background on the study?

Marc Raab, MD: The idea behind the study is that the bispecific [antibodies]—in this case, BCMA [B-cell maturation antigen]–targeting bispecifics—in myeloma are very effective in late-line therapies. Thinking about that, these patients and their T cells have already received a lot of therapy; the idea was to explore bispecific therapies in frontline settings, where patients and their T cells have not been exposed to any prior therapies. [We are] exploring combinations with standard-of-care therapies such as [daratumumab, or lenalidomide (Revlimid) and dexamethasone (LenDex)] or daratumumab, bortezomib [Velcade], and LenDex, [which are] standard in frontline therapy in myeloma, in combination with teclistamab, what we reported here, as well as in other arms in combination with talquetamab [Talvey] or with [teclistamab] and [talquetamab] together.

What were the findings presented at IMS 2025?

We presented a complete dataset, which comprised [teclistamab, daratumumab, and lenalidomide] and [teclistamab, daratumumab, and bortezomib], with 50 patients altogether and 49 evaluable patients. What we found is that the response rate was very, very high. Almost all patients achieved a CR [complete response] by the end of cycle 6. Even more impressive is that all tested patients, after 3 cycles, were MRD-negative 10^–5 and 10^–6 after 6 cycles. Overall, we had only 1 patient [for whom] we didn't have a sample to test MRD.

Of course, safety is always a concern in frontline patients. What we found here is that, overall, this was quite well tolerated with BCMA by specifics. We recommended IVIG [intravenous immunoglobulin] supplementation and antibiotic prophylaxis for the first 3 cycles, and PJP [Pneumocystis jirovecii pneumonia] prophylaxis, throughout the study. We found a grade 3 or higher infection rate of about 36%, which was mainly due to infections in the first 3 cycles, and no treatment discontinuations or grade 5 toxicities were reported.

What do you see as the next steps in this line of research?

Of course, longer follow-up [is needed] to see whether the these very early but very impressive response rates and MRD negativity rates translate into long-term treatment and disease-free survival. The big next step, to me, is whether this will, in the next trials, lead to limiting duration [of treatment], eg, 2 years of treatment then giving the patient back a treatment-free time interval.

REFERENCES:

1. GMMG-HD10 /​ DSMM-XX /​ 64007957MMY2003, MajesTEC-5 (HD10/DSMMXX). ClinicalTrials.gov. Updated October 23, 2024. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT05695508

2. Tecvayli plus Darzalex Faspro treatment demonstrates 100 percent overall response rate in transplant-eligible patients newly diagnosed with multiple myeloma. News release. Johnson & Johnson. September 29, 2025. Accessed October 13, 2025. https://tinyurl.com/mr6fct9r