Bluebird, Celgene T-Cell Therapy Eliminates Numerous Myeloma With Minimal Side Effects
Two patients with advanced numerous myeloma, a type of blood cancer affecting plasma cells, have been put into stringent accomplish remission ongoing for four and six months, respectively, by a genetically engineered T cell therapy from Bluebird Bio (BLUE) .
Another five patients treated with the same Bluebird therapy, known as BB2121, had a “very good partial response” (a real term, meaning close to a finish remission) or a partial response. None of the patients experienced severe immune-related or neurological safety issues from BB2121, the company said.
Bluebird is developing BB2121, a type of chimeric antigen receptor T-cell, or CAR-T, in partnership with Celgene (CELG) . The fresh data reported Wednesday from a phase I investigate are the very first look at BB2121’s spectacle in numerous myeloma patients no longer responding to numerous lines of prior drugs.
While still early, the positive responses and safety profile of BB2121 compare favorably to two other numerous myeloma-targeted CAR-Ts from the National Cancer Institute and a collaboration inbetween Novartis (NVS) and the University of Pennsylvania.
“We’re watching extraordinaire, early responses with BB2121 without the toxicity,” said Bluebird CEO Nick Leschly in an interview Wednesday morning. Bluebird collective the BB2121 data with me under embargo.
The relative safety of Bluebird’s CAR-T, so far, is a key distinguishing feature, particularly given the latest toxicity issues seen with an experimental CAR-T from Juno Therapeutics (JUNO) , Leschly added.
The phase one BB2121 data are being introduced Thursday at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany.
To make BB2121, Bluebird extracts immune T cells from numerous myeloma patients, and in a lab, genetically engineers them to recognize a protein known as B-cell maturation antigen (BCMA). The BCMA protein is found on malignant and healthy plasma cells. Once injected back into the patient, the altered T cells seek out and kill BCMA-containing cells.
For the phase one explore, Bluebird recruited eleven patients with numerous myeloma no longer responsive to a median of six prior therapies, including freshly approved antibody drugs like Darzalex.
The eleven numerous myeloma patients were pre-treated with two chemotherapy drugs, cyclophosphamide and fludarabine, to kill their existing T cells. Then, they were split into four groups for treatment with escalating doses of the anti-BCMA CAR-T therapy BB2121.
Wednesday, Bluebird is reporting efficacy data from the very first three dose cohorts of BB2121 encompassing nine patients. The objective response rate among the nine patients is 78%.
One of three patients treated with the lowest BB2121 dose — fifty million cells — achieved a partial response that subsequently relapsed.
All six patients treated with the next two highest doses of BB2121 — one hundred fifty million and four hundred fifty million cells — achieved objective responses. None have relapsed to date.
The two numerous myeloma patients with stringent finish remissions were treated with the one hundred fifty million-cell dose of BB2121. A stringent finish response means the elimination of all evidence of tumor anywhere in the assets. These patients remain in stringent accomplish remission for four and six months, respectively. The third patient treated at this BB2121 dose has a “very good partial response” with the elimination of minimal residual disease.
All three patients treated at the four hundred fifty million-cell dose of BB2121 have achieved a partial response with a median go after up of eight weeks.
“We have relatively little go after up, so we are certainly hopeful that we’ll see better responses emerge in these three patients. It’s just early,” said David Davidson, Bluebird’s chief medical officer.
To date, the capability of CAR-T therapies to totally eliminate cancer cells has come at a cost, mainly a severe and potentially fatal side effect known as cytokine release syndrome — a type of immune system hyper-reaction which causes high fever, muscle ache, heart and kidney problems.
More recently, Juno Therapeutics has been compelled to halt a explore of its own CAR-T therapy targeting a different protein due to fatal brain erection.
The numerous myeloma patients treated with BB2121 in the phase I explore have, to date, only experienced mild, or grade one and Two, cytokine release syndrome and grade one neurotoxicity.
“In the context of the entire [CAR-T] field where not too long ago it was assumed to see a deep clinical response it was almost a requirement to have significant cytokine release syndrome. That seems not to be the case here. The caveat is it’s early data,” said Davidson.
Novartis and the University of Pennsylvania will present data from an early probe of a challenging anti-BCMA CAR-T in numerous myeloma at the American Society of Hematology annual meeting, which starts on Saturday.
According to a research abstract with preliminary data already disclosed, one of six treated patients in the Novartis probe achieved a stringent accomplish remission. Another patient achieved a very good partial response. There were also two reports of grade three cytokine release syndrome and a report of grade four neurotoxicity.
A different anti-BCMA CAR-T tested by the National Cancer Institute demonstrated a single finish response among twelve patients that lasted for seventeen weeks before relapase but also caused significant toxicity.
Looking ahead, Bluebird intends to enroll extra numerous myeloma patients into the phase I investigate and explore higher doses of BB2121. (Two patients have already been treated with an eight hundred million-cell dose but haven’t been followed long enough to determine response.)
Barring any problems and assuming an optimal dose is found, Bluebird believes it can advance BB2121 directly into a pivotal clinical trial, which if successful, could lead to marketing approval. The regulatory path of BB2121 is basically the same used by Kite Pharma (KITE) for its CAR-T to treat lymphoma patients.
Bluebird is in charge of completing the ongoing phase I investigate. Under their collaboration agreement, Celgene would take over development of BB2121 to conduct the pivotal probe.