Teclistamab beat standard drug combinations in earlier-line myeloma

Teclistamab, an antibody engineered to grab a cancer cell with one arm and a T cell with the other, worked better than standard drug combinations when used earlier in the course of multiple myeloma: in the phase 3 MajesTEC-9 trial, it cut the risk of the cancer progressing or the patient dying by 71% against the comparison regimens, and it improved overall survival [s1]. The trade-off was toxicity, with grade 3 or 4 infections in more than four in ten patients who received it [s1].

Teclistamab is already approved for myeloma that has come back after several prior treatments. MajesTEC-9 asked whether moving it earlier — after just one to three previous lines of therapy — would beat the drug combinations doctors reach for at that stage [s1]. Multiple myeloma is a cancer of plasma cells in the bone marrow; it is treatable but not curable, and each relapse tends to respond less well than the last, which is why the order in which treatments are used matters.

What they did

The trial enrolled patients whose myeloma had relapsed after one, two, or three prior lines that included an anti-CD38 antibody and the drug lenalidomide, and randomly assigned 296 to teclistamab and 297 to the investigator's choice of two established regimens: pomalidomide, bortezomib and dexamethasone (PVd), or carfilzomib and dexamethasone (Kd) [s1][s2]. Teclistamab targets B-cell maturation antigen, a protein on myeloma cells, and CD3 on T cells, directing the immune system onto the tumour [s1]. Antimicrobial prophylaxis and immune globulin replacement were recommended, a reflection of the infection risk the drug carries [s1]. The primary endpoint was progression-free survival judged by an independent review committee [s1].

What it showed

At the interim analysis, with a median follow-up of 17.3 months, teclistamab clearly outperformed the standard regimens [s1]. Estimated progression-free survival at 18 months was 69.8% with teclistamab against 26.9% with PVd or Kd, a hazard ratio for progression or death of 0.29 (95% confidence interval, 0.23 to 0.38; P<0.001) [s1]. The depth of response followed: 65.9% of teclistamab recipients had a complete response or better, compared with 16.8% on the standard regimens (P<0.001) [s1].

Survival moved too. Estimated overall survival at 18 months was 79.2% with teclistamab and 68.6% with PVd or Kd, a hazard ratio for death of 0.60 (95% confidence interval, 0.43 to 0.83; P=0.002) [s1]. That an overall-survival benefit was already significant at an interim look is notable in a disease where later treatment lines can blur such differences.

The cost side

The benefit came with real harm. Grade 3 or 4 adverse events occurred in 84.9% of teclistamab recipients against 76.3% on the standard regimens, and grade 5 — fatal — events in 6.5% versus 3.5% [s1]. Cytokine release syndrome, an immune over-reaction that the bispecific mechanism can trigger, occurred in 66.0% of teclistamab recipients, though mostly at grade 1 or 2; immune effector cell-associated neurotoxicity syndrome, a neurological reaction, occurred in 4.1% [s1]. The starkest signal was infection: grade 3 or 4 infections occurred in 41.6% of teclistamab recipients versus 29.0% on the comparators, and remained common despite the recommended prophylaxis [s1].

What to watch

The trial was funded by teclistamab's manufacturer and was open-label, so patients and doctors knew the assignment — a design limit that matters less for the hard endpoints of progression and death than for subjective ones [s1]. The larger question is the balance the numbers describe: a substantial gain in progression-free and overall survival set against a higher rate of fatal events and serious infection. Whether regulators move teclistamab into this earlier setting, and how the infection risk is managed in routine care, are the open questions.

The result adds to a shift toward redirecting the immune system in myeloma, alongside newer oral agents such as iberdomide and related CELMoD drugs. It also echoes what T-cell-engaging bispecifics have done in other blood cancers, including blinatumomab in childhood acute lymphoblastic leukaemia, and it raises the stakes for measuring residual disease after treatment, the tool most likely to show whether deeper early responses translate into lasting control.

Sources

• [s1] Touzeau C, Mina R, Quach H, et al. Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy. New England Journal of Medicine. 30 July 2026 (published online 29 May 2026).
• [s2] ClinicalTrials.gov. A Study Comparing Teclistamab Monotherapy Versus PVd or Kd in Relapsed or Refractory Multiple Myeloma (MajesTEC-9, NCT05572515). U.S. National Library of Medicine.