Summary
A phase 1 follow-up of four patients with relapsed or refractory multiple myeloma found that one maintained a stringent complete response for 15 months. The other three progressed within five months, and median progression-free survival was 4.0 months.
A phase 1 follow-up published in Nature Medicine reports outcomes for four people with relapsed or refractory multiple myeloma who received ESO-T01, an investigational in-vivo BCMA CAR-T therapy. One patient remained in stringent complete response at 15 months. The other three experienced relapse or disease progression, and the median progression-free survival was 4.0 months (range 3.0–15.0 months).
The findings extend follow-up of a small first-in-human study, with data collected through March 2026. All four patients had initially responded, but the longer-term results show that early tumour responses did not usually last in this group.
How the in-vivo treatment was given
Conventional CAR-T treatment involves collecting a patient’s T cells, genetically modifying them outside the body and returning them as an infusion. ESO-T01 instead used a lentiviral vector infused intravenously to deliver instructions for an anti-BCMA chimeric antigen receptor to T cells inside the body. BCMA is a target found on myeloma cells. The approach was given as a single dose of 0.2 × 10⁹ transduction units, without leukapheresis or lymphodepleting chemotherapy.
The four participants had received a median of four previous lines of treatment. Their median age was 63. At their initial assessment after treatment, two had a stringent complete response and two had a partial response, giving an objective response in all four patients.
Responses and safety over follow-up
Three patients relapsed or progressed at three, three and five months after infusion. Each had extramedullary disease at progression, meaning myeloma involving sites outside the bone marrow; some also had cancer cells in the cerebrospinal fluid. All three eventually died during follow-up, despite receiving further treatment. The remaining patient, who had the lowest tumour burden at the start of the study, maintained a stringent complete response through 15 months.
The researchers report a median progression-free survival of 4.0 months. This is the time from treatment until disease progression or death, and in this four-person study it reflects the early relapses in three patients alongside the longer response in one.
All four experienced grade 1–3 cytokine release syndrome, an inflammatory reaction that can occur as CAR-T cells become active, and grade 3–4 blood-cell toxicities. One patient developed grade 1 immune effector cell-associated neurotoxicity syndrome. The paper reports that most adverse events returned to baseline or resolved within two to three months, and that no important new ESO-T01-related adverse events emerged during extended follow-up. Exploratory analyses also found no high-risk vector-integration events in the samples examined.
The results provide additional clinical follow-up for an approach designed to generate CAR-T cells in the body rather than manufacture them individually outside it. But the durability seen here was limited for three of the four participants. The researchers note that the sustained responder had lower disease burden and persistent CAR-T cells; this small study cannot determine which patient or treatment features account for the difference.
The trial was a single-arm phase 1 study and ended after ESO-T01 sponsor EsoBiotec was acquired by AstraZeneca, so no additional participants were enrolled. The four-patient cohort can describe these patients’ outcomes, but larger prospective studies are needed to assess how often responses persist and to characterize less common or delayed risks.