SAN DIEGO — Bluebird bio's lead CAR-T candidate captured the industry's attention over the last two years with promising clinical readouts. But on Sunday, it was the company's second-generation cell therapy that stood in the spotlight, as data on a small group of very sick multiple myeloma patients showed the treatment to be effective. Still unclear, however, is whether the newer treatment will ultimately outclass its predecessor.
Of the dozen patients infused with Bluebird's bb21217 by Oct. 18, 10 had an objective clinical response, according to results presented at the American Society of Hematology's annual meeting. Investigators also found that among 11 evaluable patients, all had CAR-T cell expansion over the 30 days following their respective infusions. And for the three who were evaluable at six months or more, each demonstrated "sustained persistence" of CAR-positive T cells.
That sustained persistence is key, as it's one of the main reasons Bluebird and partner Celgene are developing bb21217.
Earlier this year, a Phase 1 study testing three doses of the companies' more advanced CAR-T therapy, bb2121, in heavily pretreated multiple myeloma patients showed that the highest dose arm achieved a 96% objective response rate and a 50% complete response rate. Yet the median time before those patients' cancer progressed was just under a year — results that disappointed some analysts who had hoped to see longer durability.
With bb21217, Bluebird and Celgene tweaked their manufacturing process to create what they say will be a more potent and longer-lasting therapy. It will take more time to see whether the data support that belief, but the early findings appear to have potential.
It's worth noting, however, that only three patients were judged to have had a complete response, putting bb21217's rate below that seen with the highest dose of bb2121.
Initial results for bb21217
|# of patients who...|
|Were infused by the Oct. 18 data extract||12|
|Achieved a clinical response||10|
|Have an ongoing response||9|
|Achieved a complete response or stringent complete response||3|
|Achieved a very good partial response||2|
|Achieved a partial response||4|
Hematologists expect persistence to be a focus with CAR-T therapies as the field matures. Deepu Madduri, an assistant professor at New York's Mount Sinai Health System, told BioPharma Dive the overarching question at hand is whether having the CAR-T cells in the body for more time will in turn support prolonged responses. While the general thinking is yes, Madduri said additional data should help clear things up.
For one study that evaluated Kymriah in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia, a two-year follow-up analysis found the relapse-free survival rate was 62%, while median duration of remission and median overall survival hadn't yet been reached among evaluable patients.
"Extending the progression-free survival is what everyone is going to be so focused on, because I think it seems like we're not going to see a whole lot of unexpected toxicities going forward," Craig Hofmeister, acting associate professor in the department of hematology and medical oncology at the Emory University School of Medicine, said of CAR-T therapies during an interview with BioPharma Dive.
On the toxicities front, Bluebird said those seen so far in the Phase 1 study of bb21217 were consistent with other CAR-T therapies. Notable too is the fact that patients receiving these treatments are often very sick. Across the 12 patients infused with bb21217, they had a median of seven prior lines of therapy.
Two-thirds of the 12 infused patients experienced an immune response known as cytokine release syndrome (CRS), though only one of those cases was classified as serious. Neurotoxicities were seen in three patients, with one being mild, one being moderate and one being life-threatening. All of the CRS and neurotoxicity events were resolved and no patients on study have died, according to a Dec. 2 statement from Bluebird.
The biotech notes the bb21217 study is evaluating a higher dose of the therapy in cohorts of patients with high and low tumor burden. It also recently announced enrollment has completed for the pivotal KarMMa trial of bb2121.
Data on more patients may further validate the therapies. Still, Bluebird and Celgene appear confident in their CAR-T capabilities as well as where they stand in the larger multiple myeloma treatment landscape.
"There's been a surge of competition, and we feel that the best way to stay well ahead of that competition is to out-innovate everyone else; and so part of that means even as we're in the process of demonstrating the risk-benefit and the therapeutic potential of our drugs, [we're also] moving forward potentially even better drugs," Bluebird's Chief Medical Officer David Davidson told BioPharma Dive.
Such a strategy does open the company up to the threat of cannibalization should both its CAR-T treatments come to market. Davidson, though, said Bluebird has already weighed the pros and cons.
"We're committed to providing the best outcomes possible to our patients, and if that requires essentially superseding one product with another we've developed, we would rather be the ones doing that than having someone else do it," he said.