Teclistamab-Based Induction Regimens Deepen Responses in Newly Diagnosed Multiple Myeloma

The addition of teclistamab-cqyv (Tecvayli) to standard daratumumab (Darzalex)–based induction regimens generated high post-induction minimal residual disease (MRD) negativity rates and was deemed well tolerated in patients with transplant-eligible, newly diagnosed multiple myeloma, according to Marc S. Raab, MD.

“This study indicates that T-cell engagers like bispecific antibodies will have a role in early-line treatment, in front-line treatment, and in combination with standard-of-care [SOC] drugs, and [that these agents] can lead to deep, unprecedented responses like an MRD negativity rate of 100% in tested patients,” Raab said in an interview with OncLive® during the 22nd Annual International Myeloma Society (IMS) Meeting and Exposition.

In the interview, Raab discussed the rationale for adding a bispecific antibody to SOC daratumumab-based induction regimens for the treatment of patients with newly diagnosed multiple myeloma; updated MRD negativity and safety data with teclistamab plus daratumumab and lenalidomide (Revlimid) and teclistamab plus daratumumab, lenalidomide, and bortezomib (Velcade) in this population from the phase 2 MajesTEC-5 trial (NCT05695508); and the importance of infection prophylaxis when administering these types of regimens.

Raab is a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital, CCU Molecular Hematology/Oncology, German Cancer Research Center in Germany.

OncLive: What was the rationale for conducting the MajesTEC-5 study?

Raab: Daratumumab plus bortezomib, lenalidomide, and dexamethasone [Dara-VRd] is the SOC quadruplet induction [regimen for patients with newly diagnosed, transplant-eligible multiple myeloma] and can achieve high response rates and long durations of response. However, there’s still room for improvement, because, for example, in the phase 3 PERSEUS study [(NCT03710603) of Dara-VRd in transplant-eligible patients with newly diagnosed multiple myeloma], even after transplant and consolidation, the MRD negativity rate was [75.2%].1 The rationale for [MajesTEC-5] was to assess in a phase 2 fashion the safety and efficacy of adding a bispecific antibody—teclistamab—to SOC daratumumab, lenalidomide, and/or bortezomib.2

What were the characteristics of the patients enrolled in MajesTEC-5?

The patient characteristics in our study were as you would expect for a transplant-eligible patient population. [Patients were] relatively young, with a median age of [58.0] years. [A total of 44.9%] of the patients had high tumor load, [defined as] a bone marrow infiltration rate of [at least] 60%. [Additionally,] high-risk markers were present in [20.4%] of patients.

What was the design of MajesTEC-5?

This was a multicohort study where we tested different combinations and schedules. [Arm A received] teclistamab given weekly in combination with lenalidomide and daratumumab. We limited dexamethasone to the first 2 cycles. Then we added a cohort where we gave teclistamab in the same combination, but only monthly. We also had a cohort where we added to that monthly teclistamab schedule weekly bortezomib to resemble the PERSEUS Dara-VRd regimen.

What efficacy findings from MajesTEC-5 were presented at IMS 2025?

We presented the update of the preliminary data we [had shared] at the 2024 ASH Annual Meeting from all 3 cohorts [composed of] 49 patients. All the patients have now completed the 6 cycles of induction. The response rates deepened over time and reached almost 100% across all cohorts. The first cohort had a 100% complete response [(CR) or better] rate. The second cohort had a 95% CR [or better] rate. The third [cohort had a CR or better rate that was a] bit lower, at 73.7%; however, in approximately 4 of these patients, very good partial response at the end of induction converted to a CR after transplant. [These were] high and deep response rates.

Importantly, the already-promising MRD negativity rates we saw at ASH 2024 have now [translated to] an impressive [dataset]. All patients with available samples had MRD negativity that was reached as early as after cycle 3 and confirmed after cycle 6, at [a sensitivity of] 10–5 by flow cytometry. [MRD negativity was also tested] with next-generation sequencing [NGS] at [a sensitivity of] 10–6. [In total], 46 out of 49 patients had samples available for the NGS 10–6 testing, and all those samples were negative for MRD. [Testing yielded an] MRD negativity rate for the tested patient of 100%. Overall, 98.0% of the patients [were MRD negative by the end of induction].

What updated safety findings were seen in MajesTEC-5?

The safety, overall, was manageable. However, we need to keep an eye on infection rates, as always, when you use BCMA-directed bispecific antibodies, especially in combinations. We initially had a grade 3/4 infection rate of 34.7% that we presented at ASH 2024.3

Now, [that rate is 36.7%].2,3 That means that with longer follow-up, only 1 additional grade 3/4 infection was reported in 1 additional patient. We had no grade 5 infections, and no patients discontinued the study because of infections. However, still, infection prophylaxis is a key point if you combine a BCMA-targeting bispecific antibody with SOC drugs. Giving IVIG prophylactically, PCP prophylaxis, anti-Zoster prophylaxis, and antiviral prophylaxis is key to keeping those rates as low as possible.

What are the potential next steps and clinical implications of the updated MajesTEC-5 study results?

This is a phase 2 study, so it probably has no immediate effect on the routine care you provide to your patients. However, it opens a clear avenue [for future research]. Phase 3 trials are planned or already underway for this newly diagnosed setting, [investigating] highly effective T-cell engagers in a setting where the T cells are treatment naive. Because when the patient is newly diagnosed, [therapy is] probably most effective and most active in this stage.

References

1. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. New Engl J Med. 2023;390(4):301-313. doi:10.1056/NEJMoa2312054
2. Raab MS, Weinhold M, Kortüm KM, et al. Post-induction outcomes and updated minimal residual disease analysis from GMMG-HD10/DSMM-XX (MajesTEC-5): a study of teclistamab-based induction regimens in newly diagnosed multiple myeloma (NDMM). Presented at: 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract OA-13.
3. Tecvayli - MajesTEC-5 (MMY2003) study - Tecvayli-based regimens. Johnson & Johnson. Updated October 8, 2025. Accessed October 13, 2025. https://www.jnjmedicalconnect.com/products/tecvayli/medical-content/tecvayli-majestec5-mmy2003-study-tecvaylibased-regimens#bibRef0b6cf90f931a34b3dad4d44a0a0921537