Blenrep surprises again

Blenrep is beginning 2024 the way it ended 2023, with an unexpected clinical trial win. GSK today said the Dreamm-8 study, in which Blenrep was combined with Pomalyst in second-line multiple myeloma, was stopped early after an independent review committee found a “statistically significant and clinically meaningful” PFS benefit versus Velcade plus Pomalyst.

This mirrors last year’s unexpected win in Dreamm-7, a second-line study comparing a different regimen – Blenrep plus Velcade against Darzalex and Velcade. It keeps alive the question whether US and EU regulators, who last year pulled Blenrep's approvals in late-line disease, should now do a U-turn.

For an answer it’s likely that more data have to be presented and analysed. The Dreamm-7 results were discussed at an ASCO virtual plenary last month, showing those findings to be robust – with the caveat of Blenrep’s eye toxicity and thrombocytopenia adverse events – but not revealing much about subsequent treatment sequencing.

Two wins, one loss

The data didn't explain why the potentially confirmatory Dreamm-3 trial in later-line disease was such a disaster, and this situation looks likely to remain after today’s Dreamm-8 topline result, though perhaps the most obvious takeaway seems to be that if Blenrep is given earlier its chances of success are higher, perhaps because patients can tolerate it better.

While Dreamm-8 adds to the supporting evidence of Dreamm-7, the latter study remains more relevant in a western setting where Darzalex is moving into early treatment. The design of Dreamm-8, in a post-Revlimid population, says nothing about Darzalex use, so the Dreamm-7 setting, where Blenrep effectively beat the J&J/Genmab drug, seems more impressive in the real world.

That said, the Dreamm-8 outcome remains intriguing. As well as being positive for PFS, the primary endpoint, GSK says Dreamm-8 is also showing a “positive trend” for OS. When GSK toplined Dreamm-7 it called that trial's interim OS signal "strong and clinically meaningful", and this was later revealed as a 43% reduction in risk of death, which seemed impressive despite the very immature stage of this readout.

If the positive outcomes of Dreamm-7 and 8 come as a surprise, so does the fact that both trials had been delayed by lower than expected event accrual rates. Historically such delays have rarely been a good omen, instead indicating the recruitment of an overall population that is less ill than expected, but this case seems to be one of longer survival in the Blenrep cohort specifically.

Dreamm-10 in limbo

While GSK now has two pieces of evidence backing early Blenrep use the company still hasn’t started Dreamm-10, a front-line multiple myeloma trial it had been planning some years ago. Dreamm-10 still being in limbo suggests that GSK has some doubts, though perhaps the group is just waiting to see how regulators respond to the Dreamm-7 and 8 readouts.

The US FDA is separately mulling Car-T therapies against BCMA, whose own early-line use is subject to a 15 March advisory committee meeting. In GSK’s case regulators now have to decide whether two positive second-line trials warrant Blenrep’s approval here and/or its reinstatement in the late-line setting in which the drug was earlier shown not to work.

Key Blenrep trials in multiple myeloma

Source: prescribing information, ASCO Feb 2023 virtual plenary & OncologyPipeline.