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

Investigator says therapy provided "unheard of" responses in very sick patients.

Patients with highly advanced multiple myeloma have seen spectacular results with Bluebird Bio and Celgene’s CAR-T therapy bb2121; the disease was pushed into remission in more than half of those treated.

The 21-patient study showed an 86% overall response rate to the therapy, which mobilizes the immune system to attack cancer cells expressing the B-cell maturation antigen (BCMA). Moreover, all but one of 18 patients on a higher dose of the CAR-T saw a clinical benefit, despite being very ill with their disease progressing after a median of seven earlier treatments.

The data adds to a bevy of impressive CAR-T studies that have been a highlight of the American Society of Hematology (ASH) meeting in Atlanta, and in common with new studies for the two already-approved CAR-Ts—Novartis’ Kymriah and Gilead/Kite’s Yescarta—the results are remarkable for the high proportion of compete responses.

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Nine months after a single dose of bb2121, 56% of the patients treated with bb2121 were in complete remission, more than twice the proportion seen at the three-month timepoint presented at the ASCO meeting in May, which could indicate that the response to the therapy is building up over time. Typically, patient with multiple myeloma who have gone through three rounds of prior therapy only have around eight months to live.

Jesus Berdeja, M.D., of the Sarah Cannon Research Institute and Tennessee Oncology in Nashville, said the results are important because multiple myeloma remains largely incurable despite big advances in drug therapy that have improved overall survival from a median of three years to between eight and 10 years.

He said that bb2121 showed good tolerability in the phase 1 trial. Like most CAR-Ts the therapy was associated with cytokine release syndrome, but while this occurred in 14 patients, in most cases it was milder (grade 1 or 2), with just two patients experiencing grade 3 or higher. Similarly, neurotoxicity—another concern with CAR-T therapy—was seen in five patients, but was also only grade 1 or 2.

An expansion phase of the study is now underway along with a pivotal phase 2 trial—dubbed KAarMMa—that will enroll around 80 pretreated myeloma patients and have the primary endpoint of overall response rate. Meanwhile, Celgene is planning additional trials of bb2121 in earlier lines of therapy.

Meanwhile, a second generation anti-BCMA CAR-T called bb21217 has also started initial testing, said Bluebird.

The company has some competition out there for its BCMA-targeted approach. Novartis has a CAR-T in development (CART-BCMA) which showed “significant clinical efficacy” in a 10-patient phase 1 trial presented at ASH yesterday. And GlaxoSmithKline also reported positive results from a phase 2 study of its antibody-drug conjugate candidate GSK2857916 with an overall response rate of 60%.

Bluebird CEO Nick Leschly told analysts and reporters yesterday that this year’s ASH is a momentous one for the biotech, with new data not just in myeloma but also positive results with its LentiGlobin gene therapy candidates in sickle cell disease (SCD) and beta-thalassemia.

New clinical results from two patients in the phase 1 HGB-206 study of the SCD product—using a vector made via a refined manufacturing process—showed an improved anti-sickling effect, while data with the thalassemia product revealed durable responses in transfusion-dependent patients after up to three years of follow-up.

The company is now pushing to bring all three of these programs, plus its therapy for cerebral adrenoleukodystrophy, through to approval and launch, he added.