bb2121 induces durable, deepening responses in MM patients

Five (24%) patients experienced neurotoxicity, none grade 3 or higher.

Dr Kochenderfer described 1 case of delayed-onset, grade 4, reversible neurotoxicity that was associated with tumor lysis syndrome (TLS) and CRS.

The patient had no toxicity until day 10. By day 12, magnetic resonance imaging showed cerebral edema.

The patient was transferred to the intensive care unit and required intubation. She was treated with high-dose methylprednisolone and tocilizumab. She also received hemodialysis for TLS.

“By day 17, she dramatically improved,” Dr Kochenderfer said.

Her mental status cleared, TLS resolved, she was extubated, and she was doing much better, he reported.

On day 30, the patient was out of the intensive care unit.

“So the whole course was fairly brief,” Dr Kochenderfer said. “And, today, she’s doing well. She’s actually asymptomatic.”

Cytopenias—neutropenia, thrombocytopenia, and anemia—were primarily related to the lymphodepleting drugs, and patients recovered to grade 3 or lower by month 2 after the infusion.

Fourteen patients experienced 1 or more serious adverse events. Four had grade 1-2 CRS that required hospitalization per protocol, and 2 had pyrexia.

Five patients died, 3 due to disease progression, all who received treatment at the lowest dose.

Two patients treated at active doses were in CR when they died. One had a cardiac arrest, and the other had myelodysplastic syndrome following discontinuation.

Efficacy

In addition to the high ORR (94%) and CR rate (56%) in this study, 9 of 10 patients evaluated for minimal residual disease were negative.

The median time to first response was 1.02 months, and median time to best response was 3.74 months. The median time to CR was 3.84 months.

The median duration of response and PFS have not been reached. The PFS rate was 81% at 6 months and 71% at 9 months.

“We found that all the doses between 150 million and 450 million were effective,” Dr Kochenderfer noted. “We didn’t see a clear difference in efficacy between those doses, so we’ve chosen to use the 150 – 300 million dose range for the follow-up study.”

The investigators observed robust expansion of bb2121, which peaked in the first week after the infusion. Six of 13 patients had evident CAR T cells at 6 months. One patient has persistence over 12 months.

The investigators also observed a robust decrease in M protein and rapid clearance of serum-free light chains and serum BCMA. They noted that the activity of the CAR-positive T cells was not inhibited by high baseline serum BCMA.

Four patients progressed. The investigators analyzed the patients’ tumor burden, bb2121 dose, best response, time to progression, BCMA expression, grades of CRS, and bb2121 persistence. And progression was independent of these factors.

“So we can’t pick out a very good factor of why they progressed,” Dr Kochenderfer said.

However, he noted that the patients are eligible for re-treatment.

Investigators have opened a global trial of bb2121 (NCT03361748) given at doses ranging from 150 – 300 million CAR T cells.

The US Food and Drug Administration and the European Medicines Agency recently fast-tracked bb2121.

*Data presented differ from the abstract.