Bispecific antibodies

AALL1731 brings immunotherapy into the front-line treatment of the commonest childhood cancer, in the group of children where most relapses were occurring despite good initial risk. Blinatumomab was approved for this use in 2024 and paediatric protocols worldwide are being amended. Whether it can allow less chemotherapy, and its effect on very low-risk children, are the next questions.

For the first time a new drug has beaten pembrolizumab, the global first-line standard, in a randomised lung cancer trial, and it did so by combining checkpoint blockade with anti-angiogenesis in one molecule. For patients outside China nothing changes yet: the drug is not approved in the West, the trial was single-country, and survival benefit has not been shown. If confirmed in the global HARMONi-3 and HARMONi-7 trials, PD-1 x VEGF bispecifics could replace PD-1 antibodies as the immunotherapy backbone.

E1910 changed the standard of care for adult B-ALL: immunotherapy is now part of front-line consolidation even for patients with no detectable leukaemia, because MRD-negative by flow cytometry does not mean cured. It also demonstrated that a T-cell engager can improve overall survival in a curative setting. Chemotherapy-light or chemotherapy-free regimens built on blinatumomab and inotuzumab are the next step.

Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.

Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.

CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.

Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.

Teclistamab showed that an off-the-shelf bispecific can approach CAR-T-like response rates in late myeloma, giving patients who cannot wait for or access cell therapy a real option. It also exposed the price: prolonged T-cell engagement causes profound immunosuppression, so infection prophylaxis and immunoglobulin replacement are now routine. Less frequent dosing after response is being adopted to reduce this burden.