Update on bb2121, Potential Advanced Multiple Myeloma Therapy, Set for ASCO 2018

Celgene’s investigational and second-generation CAR T-cell therapy bb2121 is showing real promise in treating advanced multiple myeloma patients, those with relapsed or refractory disease, updated Phase 1 data is expected to show.

An earlier analsyis showed that, among patients receiving doses of 150 million cells or higher, 94 percent responded to the treatment, including 56 percent with complete tumor eradication seen on imaging scans.

Newer results — to be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting running June 1–5 in Chicago — will include more treated patients and five additional months of follow-up.

Noopur S. Raje, MD, with the Massachusetts General Hospital Cancer Center, will give the oral presentation, titled “BB2121 anti-BCMA CAR T cell therapy in patients with relapsed/refractory multiple myeloma: Updated results from a multicenter Phase 1 study.”

T-cells, a type of white blood cell, recognize foreign molecules through specific membrane receptors. T-cell receptors can be genetically altered to specifically recognize and kill tumor cells, a therapy called chimeric antigen receptors (CAR) T-cell therapy.

CAR T-cell therapy requires taking blood from the patient, isolating T-cells, changing the cells genetically to attack proteins associated with cancer, and then infusing them back into the patient. In the case of bb2121, the therapy was designed to target the B-cell maturation antigen (BCMA) protein, which is present in multiple myeloma cells.

Clinical testing of bb2121, along with another candidate therapy — bb21217 — is being carried out under a recently announced partnership between bluebird bio and Celgene.

The ongoing Phase 1 study (NCT02658929) is two-fold. In part 1, patients will receive escalating doses of bb2121 to determine the treatment’s safety and efficacy. Patients will then be followed for up to two years.

Celgene announced results from the first 18 patients treated with 150 million cells or more in December. They showed a 94 percent response rate to bb2121, including 10 patients (56%) with complete response or unconfirmed complete response.

Of the 10 patients evaluated for minimal residual disease — a measure of therapy effectiveness in multiple myeloma — nine were negative. Minimal residual disease refers to the small numbers of cancer cells that remain in the bone marrow or blood but are undetectable by current imaging approaches.

Six and nine months after entering the trial, 81 percent of patients were still alive and 71 percent showed no signs of disease worsening. The therapy had an acceptable safety profile with no severe toxicity affecting the nervous system (neurotoxicity).

New data at the ASCO meeting will cover 20 additional patients as well as five more months of follow-up, an abstract on the presentation states without giving details.

“Cancer research is at a critical point where advances in cellular immunotherapy may be able to drive previously unattainable advancements,” Nadim Ahmed, president of hematology and oncology for Celgene, said in a press release.

The U.S. Food and Drug Administration granted bb2121 breakthrough therapy status for relapsed or refractory multiple myeloma in November 2017. It also received a PRIority MEdicines (PRIME) designation by the European Medicines Agency.