J&J Is Using Two Tecvayli Trials to Own Myeloma’s First Relapse Whether or Not Patients Had Darzalex
Five days after a CHMP opinion for Tecvayli on its own, Johnson & Johnson published modelling that projects an 86.6% cure fraction for Tecvayli with Darzalex. Behind both sit two Phase 3 trials that divide second-line multiple myeloma by prior anti-CD38 exposure, and Darzalex’s own move into earlier disease is deciding which half grows.
The CHMP recommended on 18 September 2026 extending Tecvayli (teclistamab) to adults with relapsed or refractory multiple myeloma after at least one prior therapy, as monotherapy, on the Phase 3 MajesTEC-9 trial. The European Commission had already approved Tecvayli with daratumumab as early as second line in August, on MajesTEC-3, and the FDA approved the same combination on 5 March.
MajesTEC-3 compared Tecvayli plus daratumumab with daratumumab-based triplets and cut the risk of progression or death by 83%, with 83.4% of patients progression-free at three years against 29.7%. MajesTEC-9 tested Tecvayli alone in patients already exposed to an anti-CD38 antibody and lenalidomide, and cut the risk of progression or death by 71% and of death by 40%.
On 23 September J&J reported modelling from MajesTEC-3 that estimates an overall survival cure fraction of 86.6% against 0% on standard care, and remaining life expectancy of 18.5 years against 4.9. It is a projection from three years of data.
The monotherapy carries a visible safety cost: grade 5 adverse events in 6.5% of patients against 3.5% on standard care, and grade 3 or 4 infections in 41.6% against 29.0%.
Pfizer’s Elrexfio beat daratumumab, pomalidomide and dexamethasone in its own Phase 3 in April, and AllSci reports positive Phase 3 results for AbbVie’s etentamig. J&J is ahead on labels and on overall survival; the field is closing.
A reader can stop here with the full picture. The sections below are the detail.
The two trials split first relapse by anti-CD38 exposure
MajesTEC-3 put daratumumab in both arms. Patients received Tecvayli with subcutaneous daratumumab, or daratumumab and dexamethasone with pomalidomide or bortezomib. The trial asked whether adding a BCMA bispecific to Darzalex beats a Darzalex triplet, which makes it a design for patients whose disease can still be treated with daratumumab.
MajesTEC-9 started where that population ends. It enrolled patients with one to three prior lines who had already received an anti-CD38 antibody and lenalidomide, and J&J describes them as predominantly refractory to both. There, Tecvayli alone beat pomalidomide, bortezomib and dexamethasone or carfilzomib and dexamethasone, with a hazard ratio for progression or death of 0.29 and for death of 0.60, and 65.9% of patients reached a complete response or better against 16.8%.
Read together, the trials give J&J a regimen for each branch of the same decision at first relapse. If daratumumab is still an option, add Tecvayli to it; if it has been used and failed, give Tecvayli alone. Both European indications are worded after at least one prior therapy, so the branch logic sits in the evidence rather than the label.
Darzalex’s move into earlier disease decides which half grows
J&J is steadily moving daratumumab earlier. Darzalex Faspro won FDA approval as a single agent in high-risk smoldering myeloma in November 2025, and in combination with bortezomib, lenalidomide and dexamethasone for newly diagnosed patients ineligible for transplant in January 2026, according to Halozyme’s filings.
Every patient who receives daratumumab up front reaches first relapse already exposed to it. That shrinks the population MajesTEC-3 was designed for and enlarges the one MajesTEC-9 was designed for. J&J’s frontline success with Darzalex is manufacturing the monotherapy market for Tecvayli.
J&J’s frontline success with Darzalex is manufacturing the monotherapy market for Tecvayli.
Pfizer is reading the same shift. Its MagnetisMM-32 trial evaluates Elrexfio specifically in patients previously treated with an anti-CD38 antibody. That is the population where J&J now has an overall survival result and a CHMP opinion, and where Pfizer is still enrolling.
| Trial | Regimen | Comparator | Population | Result | Status |
|---|---|---|---|---|---|
| MajesTEC-3 | Tecvayli + daratumumab | DPd or DVd | 1 to 3 prior lines | PFS risk down 83%; about 83% alive at 3 years | FDA March 2026; EC August 2026 |
| MajesTEC-9 | Tecvayli alone | PVd or Kd | 1 to 3 prior lines, anti-CD38 and lenalidomide exposed | PFS HR 0.29; OS HR 0.60 | CHMP positive, 18 September 2026 |
| MagnetisMM-5 | Elrexfio alone | DPd | 1 or more prior lines, including lenalidomide and a proteasome inhibitor; 497 patients | PFS met at interim; figures not released at topline | Topline April 2026; OS maturing |
Sources: Johnson & Johnson releases of 5 March, 18 September and 23 September 2026; International Myeloma Foundation summary of MajesTEC-3; Pfizer release of 29 April 2026 and Applied Clinical Trials. Cross-trial comparison is indicative only: populations, comparators and follow-up differ.
Pfizer’s first early-line win lands where J&J already holds labels
MagnetisMM-5 compared Elrexfio monotherapy with daratumumab, pomalidomide and dexamethasone in 497 patients across 26 countries, and met its progression-free survival endpoint at an interim analysis by blinded central review. Overall survival, a key secondary endpoint, continues.
Its comparator contains daratumumab, which places it in the same early-relapse segment as MajesTEC-3. There, J&J has approvals on both sides of the Atlantic and an overall survival benefit, while Pfizer has a topline press release. Pfizer’s argument will be a single agent against J&J’s doublet; J&J’s will be survival data Pfizer does not yet have.
AllSci reports that AbbVie’s etentamig has also produced positive Phase 3 results in relapsed or refractory disease. The BCMA bispecific class is converging on the same second-line patients, and the differentiation will come from survival, dosing burden and the partner drugs each company can supply.
The monotherapy’s safety cost is written into the data
J&J frames the MajesTEC-9 safety profile as consistent with what is known, and points out that patients stayed on Tecvayli almost twice as long as on standard care, 13.1 months against 7.0. The raw rates still favour the comparator.
Source: Johnson & Johnson, 18 September 2026, citing Touzeau et al., NEJM 2026. Rates are not adjusted for the longer treatment exposure on Tecvayli.
Grade 3 or 4 infections ran at 41.6% against 29.0%, and J&J says severe infection rates fell over time. Grade 5 events ran at 6.5% against 3.5%, even as overall survival favoured Tecvayli. For treating centres, that means infection prophylaxis and monitoring capacity become part of the cost of moving a bispecific earlier.
An 86.6% cure fraction is a model, and payers will price the model
The modelling J&J released on 23 September uses a relative survival mixture cure model built on MajesTEC-3’s progression-free and overall survival data. It estimates that about 87% of patients on the combination may have a mortality risk similar to the general population of the same age, projects remaining life expectancy of 18.5 years against 4.9, and predicts median overall survival nearly four times longer than with standard care.
A separate post hoc analysis found the combination cut the cumulative incidence of progression by 90%, with no significant difference in non-relapse mortality between the arms. That supports J&J’s argument that the survival benefit comes from disease control rather than from fewer deaths from other causes.
Both analyses are for presentation at the International Myeloma Society meeting, and both extend three years of follow-up into decades. The treatment question is duration. MajesTEC-3 permits treatment until progression, and a published cost-effectiveness analysis comparing the combination with cilta-cel capped teclistamab costs at 48 months in its base case to reflect likely payer constraints. A regimen modelled as curative but given indefinitely is the scenario European payers will test first.
J&J’s own CAR-T sits in the same line
Carvykti, the CAR-T J&J sells with Legend Biotech, is already used from first relapse in lenalidomide-refractory disease on the CARTITUDE-4 data. The same cost-effectiveness analysis set the Tecvayli combination directly against cilta-cel, which shows the two are already being weighed as alternatives.
The trade-off is logistics. Tecvayli is an off-the-shelf subcutaneous injection that J&J says can be given across practice settings, while CAR-T needs manufacturing slots and specialist centres. For J&J, whichever the physician chooses stays inside the portfolio; for competitors, the space between the two is where a single-agent bispecific has to fit.
- August 2022First EU approvalAfter at least three prior therapies.
- 5 March 2026FDA approves Tecvayli with Darzalex FasproAfter at least one prior line; Tecvayli alone converts to traditional approval in later lines.
- 29 April 2026Pfizer’s MagnetisMM-5 reads outElrexfio beats DPd on progression-free survival at interim.
- June 2026CHMP backs the combinationOn MajesTEC-3.
- August 2026EC approves the combinationAs early as second line.
- 18 September 2026CHMP backs Tecvayli aloneOn MajesTEC-9, after at least one prior therapy.
- 23 September 2026Cure-model data released86.6% modelled cure fraction, for presentation at IMS 2026.
What to watch
The Commission decision on the monotherapy, due within about two months of the CHMP opinion, which would give J&J both branches of the first-relapse decision in Europe.
Pfizer’s full MagnetisMM-5 data and overall survival, and the timing of MagnetisMM-32 in anti-CD38-exposed patients, the segment that grows as Darzalex moves earlier.
National pricing in Europe, where the cure model meets treatment until progression. How payers handle duration will shape the value of every bispecific that follows into second line.
J&J’s second-line position is built less on either trial than on the sequence they form with Darzalex. The more successfully it sells daratumumab up front, the more patients reach first relapse needing exactly the drug it now has two Phase 3 wins for.