ASCO: GSK Bolsters ADC Blenrep's Case in Multiple Myeloma Post CAR-T Success

GSK has revealed promising new data for Blenrep, an antibody-drug conjugate (ADC) aimed at treating multiple myeloma, at the American Society of Clinical Oncology (ASCO) 2024 annual meeting in Chicago. This data comes from the DREAMM-8 trial, marking the second positive phase 3 trial for the drug, and it is expected to support Blenrep's return to the U.S. market after a previous withdrawal.

The DREAMM-8 trial demonstrated that Blenrep, when combined with Bristol Myers Squibb’s Pomalyst and the steroid dexamethasone, reduced the risk of cancer progression or death by 48% compared to a combination of Takeda’s Velcade, Pomalyst, and dexamethasone. This trial included patients with multiple myeloma who had undergone at least one prior therapy. After a median follow-up period of 21.8 months, the median progression-free survival (PFS) had not been reached in the Blenrep group, compared to 12.7 months in the control group.

This follows earlier positive results from the DREAMM-7 trial, where Blenrep showed a 59% improvement in PFS over Johnson & Johnson’s Darzalex in combination treatments. These findings have fueled GSK's optimism that Blenrep could be successfully reintroduced to the market. The drug was previously withdrawn due to a failed phase 3 trial as a monotherapy.

Hesham Abdullah, M.D., head of oncology R&D at GSK, indicated that the company plans to submit Blenrep for FDA approval in the latter half of this year. If approved, Blenrep will compete in the second-line treatment space against powerful BCMA CAR-T therapies like Johnson & Johnson and Legend Biotech’s Carvykti and Bristol Myers’ Abecma.

During a press briefing at the ASCO meeting, Suzanne Trudel, M.D., from Princess Margaret Cancer Centre, and Oreofe Odejide, M.D., from Dana-Farber Cancer Institute, underscored the potential of Blenrep to become a viable treatment option for relapsed myeloma. They highlighted that Blenrep would offer a more accessible off-the-shelf treatment compared to CAR-T therapies, which have complex manufacturing processes and require administration at specialized centers.

Comparatively, Carvykti demonstrated a 59% PFS benefit in its CARTITUDE-4 trial, while Blenrep's DREAMM-8 trial showed a 48% improvement. However, GSK remains confident in the overall survival benefit observed in their earlier DREAMM-7 trial, where Blenrep preliminarily reduced the risk of death by 43% compared to the control group.

Significant differences were noted between the DREAMM trials. In DREAMM-7, around half of the participants had previously tried BMS’ Revlimid, with 30% being refractory to it. In DREAMM-8, all participants had prior exposure to Revlimid, with 80% showing resistance.

The CAR-T therapies have been associated with early death risks due to the lengthy production timelines, which delay treatment. In contrast, Blenrep did not show an early death signal, making it a potentially more accessible option for community-based treatment settings, where most myeloma patients are treated.

Abdullah emphasized that Blenrep's advantages lie in its accessibility, consistency of treatment effects across various patient subgroups, and its overall survival benefits. While J&J/Legend and BMS are advancing their CAR-T therapies to phase 3 trials for first-line treatment, GSK is taking time to thoroughly analyze Blenrep's data and consider its strategy for earlier-line settings.