Applying MajesTEC-3 Findings to a Patient With Early Relapsed Myeloma

The FDA approval of teclistamab (Tecvayli) plus daratumumab (Darzalex) has begun to reshape the treatment paradigm for early relapse of multiple myeloma. During a Case-Based Roundtable event for oncologists in the Chicago area, Patrick Hagen, MD, associate professor at Loyola Medicine in Melrose Park, Illinois, discussed the case of a patient considering second-line therapy and how the results of the MajesTEC-3 trial (NCT05083169) now factor into shared decision-making.

CASE SUMMARY

A 50-year-old woman with relapsed/refractory multiple myeloma presents to the clinic with evidence of disease progression after receiving a quadruplet regimen and autologous hematopoietic stem cell therapy.

• ECOG performance status: 1
• International Staging System (ISS) class: I
• High-risk cytogenetics present.
• The patient has a full-time job and is the primary caregiver for her parents.
• Due to her career and family obligations, the patient does not want chimeric antigen receptor (CAR) T-cell therapy.

Targeted Oncology: Could you describe the background of the MajesTEC-3 trial?

Patrick Hagen, MD: I think most of us have heard about this trial presented at ASH [American Society of Hematology Annual Meeting] and the New England Journal of Medicine.¹ It’s a big randomized phase 3 trial. They took patients who have relapsed/refractory myeloma who had 1 to 3 prior lines of therapy, standard drugs, a proteasome inhibitor and immunomodulatory drug, and who couldn’t have any prior BCMA [targeted therapy]. That’s important, particularly in today’s world. Patients who were refractory to anti-CD38 were excluded. Patients were then randomly assigned 1:1 to either teclistamab/daratumumab or standard triple regimen, daratumumab/pomalidomide (Pomalyst)/dexamethasone or daratumumab/bortezomib (Velcade)/dexamethasone, standard dosing schedule. Progression-free survival [PFS] is a primary end point, and all the important secondary end points we look at here in terms of response, minimal residual disease, overall survival [OS], and symptomatology.

We just have been treating some of our first patients with this commercially, and the MajesTEC-3 platform has a pretty convenient dosing schedule. They get standard step-up dosing with teclistamab on days 2, 4, and 8. Daratumumab is given on day 1, and that was based on some early data when they saw less toxicity if they led with the daratumumab, and then as they move forward following that, on day 8, 15, 22, and cycle 2 onward, the teclistamab goes with the daratumumab, so it mimics the daratumumab dosing schedule. Also importantly, dexamethasone was only given as part of the step up, so on the teclistamab-daratumumab arm, there was pretty minimal dexamethasone or steroid exposure once you get patients past the step-up doses.

They have to do observations after their step-up dose, and eventually the dosing becomes more convenient monthly, but only after 6 months [if] patients are in complete response. …That’s not always how we give it, but at least when it was studied, that was the dosing.

Who made up the patient population in this trial?

The baseline characteristics between the 2 arms, the teclistamab/daratumumab vs the triplet standard of care, were well matched in terms of performance status, age, [staging], and refractoriness. [There was] about 35% with high-risk cytogenetics in both arms, which is about what we would expect with 1 to 3 prior lines of therapy, because the more times patient’s relapse, the more high-risk features. It’s pretty well matched and pretty representative of what we would expect in this patient population.

What were the efficacy outcomes of this trial?

It was a positive study. The median PFS so far has not been reached in the teclistamab/daratumumab arm, vs 18 months in the triplet arm. At 36 months out, or 3 years, 83% vs about 30% are still progression free, [respectively]. Response rates and depth of response are much higher on the teclistamab/daratumumab arm and then the 36-month OS is again higher in the teclistamab/daratumumab arm, although obviously the survival difference isn’t as impressive as the PFS…83% vs 65%. The OS is significant, so there is a difference, but obviously not as big of a difference.

Duration of response mimics what we see in terms of overall response and PFS. With teclistamab/daratumumab, [most responders] have gone at least 3 years without relapsing: similar numbers to the PFS; 88% vs 36% between the 2. [There are] responses that are holding and potentially seeing a plateau. But be a little careful of the numbers [of patients] at risk. Not a lot of patients are in follow-up [58 vs 21 at 3 years], but there is a good duration of response in those who are responding.

_{DISCLOSURES: Hagen previously disclosed serving on the speaker’s bureau for Sanofi.}

REFERENCES

1. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. Published online December 9, 2025. doi:10.1056/NEJMoa2514663

2. Tecvayli. Prescribing information. Janssen, 2022. Accessed April 13, 2026. https://tinyurl.com/ykr92w92