The candidate CAR-T cell therapy bb2121 showed a favorable safety profile and eliminated traces of cancer in nearly half of heavily pre-treated multiple myeloma patients included in a Phase 1 clinical trial, interim results show.
The study, “Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma,” reports the first safety and efficacy results from its dose escalation and expansion part involving the first 33 enrolled patients, who were followed for a minimum of six months.
The report was published in the journal The New England Journal of Medicine.
Celgene and bluebird bio are collaborating to develop bb2121, an investigational chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen, a protein present on the surface of myeloma cells.
They are conducting the Phase 1 CRB-401 trial (NCT02658929) in the U.S. to gather preliminary safety and efficacy data on bb2121 to treat patients whose myeloma came back (relapsed) or failed to respond (refractory) to several standard treatments.
The study consists of two parts: part A, a dose-escalation study, in which several doses of a single bb2121 infusion are tested (ranging from 50 million to 800 million CAR T-cells); and part B, an expansion phase in which subjects are infused with the recommended dose identified in part A.
The interim data published refers to the first 33 patients who received a bb2121 infusion in this study, with a follow-up period of 6.2 months.
The most common serious or life-threatening adverse events were blood-related toxic effects including low counts for several blood components including neutrophils, a type of white blood cell (in 85% of the patients), white blood cells in general (58%), red blood cells or anemia (45%), and platelets (45%).
Many patients (76%) experienced cytokine release syndrome, a widespread inflammatory response involving a wide and rapid release of cytokines (key immune messengers) into the blood by the immune cells affected by the therapy. This condition was severe in two patients, but was reversible in all.
Neurologic toxic effects were observed in 14 patients (42%), and were mild to moderate in almost all. One patient experienced a life-threatening neurologic effect, which was reversed.
Infection developed in 14 patients (42%), two of whom had severe events (anal abscess and parvovirus infection).
Preliminary efficacy results showed that 85% of patients responded to the treatment, including 45% with a complete response and 27% who reached a very good partial response.
A complete response refers to patients with a low percentage of plasma cells in the bone marrow and no evidence of myeloma proteins in the serum or urine as measured by standard laboratory techniques. A very good partial response corresponds to a greater than 90% drop in myeloma proteins.
All of the 16 patients who responded to treatment tested negative for minimal residual disease at one or more time points, meaning they reached a very low concentration of myeloma cells — less than one in a thousand total cells — in the blood.
The patients responded early to the bb2121 infusion, taking a median of one month to start seeing a partial response or greater.
In addition, responses were durable, meaning they persisted a median of 10.9 months. CAR T-cells remained detectable in the blood of 57% of patients at six months and 20% of patients one year following the infusion.
Blood CAR T-cell levels were higher in patients who responded to the treatment than those who did not.
The median time to disease worsening or death was 11.8 months.
“We are encouraged by the expansion and persistence of the CAR T-cells, as well as the deep and durable responses with a manageable safety profile we’ve seen for bb2121 to date,” James N. Kochenderfer, MD, investigator at the National Cancer Institute, Center for Cancer Research, and the study’s senior author, said in a press release.
Alise Reicin, MD, president for Celgene’s global clinical development, stated: “The compelling data in these heavily pre-treated relapsed/refractory patients has provided important insights in the development of bb2121 as we continue the follow up of patients in our recently fully enrolled pivotal KarMMa trial. We are also evaluating the potential for bb2121 in earlier lines of multiple myeloma treatment in the other KarMMa trials.”
In 2017, bb2121 was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) and PRIority Medicines eligibility by the European Medicines Agency (EMA) based on preliminary clinical data from the CRB-401 study.
Celgene and bluebird bio hope to get FDA approval for bb2121 in the second half of 2020, but this depends on the treatment’s safety and efficacy results, which have yet to be established by the clinical studies.