- Two new CAR-T therapies targeting a protein known as BCMA showed startlingly positive early signs of efficacy in multiple myeloma patients, according to research presented Monday at the annual meeting of the American Society for Clinical Oncology (ASCO).
- CAR-Ts to date have been aimed at leukemias and lymphomas, with little evidence of success outside of that setting. But data from Cambridge biotech Bluebird Bio and little-known Nanjing Legend Biotech out of China give proof CAR-T treatment may have broader applicability.
- "The validation of this target, between us and Legend, that’s out of the park. That is just irrefutable at this point," said Bluebird Bio CEO Nick Leschly in an interview Monday.
Legend earned a spot as one of the many consequential late-breaking abstracts presented at ASCO this weekend. And it certainly lived up to that billing.
Thirty-three out of 35 patients with relapsed, refractory multiple myeloma showed evidence of clinical remission (defined as either a complete response or very good partial response) within two months of receiving Legend’s LCAR-B3M CAR-T cells. Overall objective response rate was 100% and of the 19 patients who had been followed for more than four months, 14 achieved a stringent complete response.
Cytokine release syndrome (CRS) was seen in more than eight out of 10 patients, but the majority of cases were transient and rated Grade 1 or Grade 2.
Bluebird’s data was just as impressive, albeit in a slightly smaller number of patients. Treatment with its BCMA-targeting CAR-T, known as bb2121, triggered an objective response in 100% of the 15 evaluable patients at the three doses which showed activity. Four registered a complete response.
Three other patients in the analysis were treated at a fourth, lowest dose and later died. Including those patients, the overall response rate across the evaluable cohort was 89%.
Only two patients experienced Grade 3 CRS but that resolved within 24 hours for both patients. Lower-grade CRS was present in 71% of patients but was manageable.
While the two sets of impressive data will invite comparison, the early nature and differences between each CAR-T complicate analysis. More importantly for the CAR-T field, however, BCMA and multiple myeloma now looks like the next step in a rapidly emerging field.
"As we see the evolving risk-benefit profile look very favorable for BCMA and CAR-Ts, you begin to think about moving to an earlier stage therapy with these patients with CAR-T," said David Davidson, chief medical officer at Bluebird Bio.
Bluebird Bio sees Legend’s results as another clear signal of the ability to target BCMA with a CAR-T. But Leschly made a point to note what Bluebird sees a key differences between the patient populations studied in Bluebird’s trial and Legend’s.
All 21 patients enrolled and dosed in Bluebird's study had at least one prior autologous stem cell transplant and were heavily pre-treated, receiving a median of seven prior therapies.
"The other data, as exciting as it is, it is a very different population," Leschly said. "It is three lines of prior therapy."
Bluebird plans to move bb2121 into an expansion stage at one of the three higher, active doses and is planning for a pivotal trial.
And the biotech has a powerhouse partner, Celgene, to help it develop bb2121. The two first struck a collaboration deal in 2013 but have since amended it to focus exclusively on anit-BCMA products.
Celgene exercised its option for an exclusive license to commercialize bb2121 in February of 2016, but Bluebird can elect to co-develop and co-promote the compound at the end of Phase 1 testing — a step Bluebird currently plans to take.
Shares in Bluebird Bio closed up 8.5% Monday.