ASCO: Bluebird and Celgene’s CAR-T nears 1 year of PFS in multiple myeloma

Red blood cells
With larger infusions of Bluebird and Celgene's CAR-T cells, patients went a median of 11.8 months without disease progression, while those who tested positive for remission went an additional six months, all regardless of BCMA expression. (Wikimedia Commons)

Bluebird Bio and Celgene have built upon their already impressive early-stage clinical responses in advanced multiple myeloma, now confirming that their bb2121 CAR-T therapy extended progression-free survival to just shy of one year in a new set of phase 1 data.

In 18 participants receiving larger infusions of 150 million CAR-T cells or more—engineered to target B-cell maturation antigen, or BCMA, a protein on the surface of certain myeloma cells—the dose-escalation study saw a median PFS of 11.8 months. Meanwhile, the 16 patients across the study who tested negative for minimal residual disease demonstrated a median PFS of 17.7 months, according to the companies’ presentation Friday at the annual meeting of the American Society of Clinical Oncology in Chicago.

Additionally, the new data showed little difference in overall response rates between patients with low or high levels of BCMA expression at high doses, meaning that future patients will not need to be segmented or tested with a diagnostic—an important distinction to note as the two companies look to file bb2121 with the FDA before the end of 2019, Bluebird CEO Nick Leschly told FierceBiotech.

Last December, in a presentation at the American Society of Hematology’s annual meeting, the companies demonstrated an 86% overall response rate, with 56% of patients in remission nine months after a single dose.

Now, the study—which has been expanded from 21 to 43 patients—also showed no new safety signals, including severe or fatal cases of cytokine release syndrome or neurotoxicity. While 63% of patients had a CRS event, the companies described them as manageable.

“That safety profile is incredibly important,” Leschly said. “Not only because you want it for patients, but also if you want to consider using this treatment in earlier myeloma patients, which we certainly do.”

Currently, bb2121 is being tested in heavily-treated multiple myeloma patients whose disease had relapsed after becoming refractory to multiple standard therapies. Two deaths in the study had been reported at ASH, linked to cardiac arrest and myelodysplastic syndrome. Both patients had demonstrated complete responses at their last assessments.

RELATED: Bluebird and Celgene’s CAR-T hits the mark in myeloma

This year, Bluebird and Celgene hope to begin pursuit of bb2121 in earlier indications, step-by-step, Leschly said—including a planned phase 3 trial in third-line multiple myeloma compared to a triplet regimen of daratumumab (Genmab and Janssen’s Darzalex) plus pomalidomide (Celgene’s Pomalyst) and dexamethasone, a corticosteroid.

After that, the companies plan to explore label expansions in second-line therapy, followed by exploration in newly diagnosed disease compared to stem cell transplants.

“We believe our profile of efficacy and safety is very conducive to starting to move earlier lines of treatment,” he said. “That’s ultimately where the game will be played.”

RELATED: Bluebird, Celgene to share U.S. costs, profits on lead cancer CAR-T

Enrollment in a pivotal phase 2 trial, KarMMa, is already underway, which will be used to support the expected 2019 filing in later lines of treatment. The study plans to examine overall response rate in 80 relapsed and refractory patients who have previously received three or more treatment regimens.

KarMMa’s design also dovetails nicely with the phase 1 results, Leschly described, with certain elements being baked into the protocol along the way, such as aims for the higher end of the dose range and no delineation based on BCMA expression.

“As you now have refined and more targeted doses, one could hope that this data would be as good, if not better, over time,” he said. “But that’s what we need to go show.”

Analysts at Jefferies said in a note to clients released over the weekend that "Contrary to fears that efficacy would fall off or durability would not hold up, new updated bb2121 data looks solid at ASCO with around 50% CR rate. We think data looks quite good especially in very sick population and supports blockbuster pot'l for CELG and supports their broad-based BCMA pipeline."

Bluebird bio was down 4.6% premarket Monday morning on the ASCO update, while partner Celgene, which is presenting data across several other marketed and experimental cancer drugs, was marginally up by nearly 1%. 

Editor's note: This story was updated to clarify the PFS of patients who tested negative for minimal residual disease.