CAR-T Cell Therapy Shows Promise in Early Trial Among Patients with Multiple Myeloma

Treatment with bb2121 — a chimeric antigen receptor (CAR)-T cell therapy candidate – showed promising efficacy and safety among heavily pretreated patients with multiple myeloma, according to interim results published in the New England Journal of Medicine.

"CAR-T cell therapy is an important area of research for relapsed/refractory multiple myeloma patients where there remains a need for new options,” senior author and principal investigator Dr. James N. Kochenderfer, from the Experimental Transplantation and Immunology Branch at the National Cancer Institute Center for Cancer Research, said in a press release. “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.”

In the ongoing phase 1 study, 33 consecutive patients received a bb2121 infusion, administered at doses of 50×10⁶, 150×10⁶, 450×10⁶ or 800×10⁶ CAR-T cells in the dose-escalation phase and 150×10⁶ to 450×10⁶ CAR-T cells in the expansion phase. In this portion of the study reported in NEJM, safety outcomes served as the primary endpoint.

Patients in the study were heavily pre-treated, with a median of seven prior treatment regimens, including immunomodulatory drugs, proteasome inhibitors and Darzalex (daratumumab), while all but one patient had an autologous stem cell transplant.

After data cutoff of 6.2 months following last infusion, hematologic toxic effects were the most common grade 3 or higher side effects. These included neutropenia (85%), leukopenia (58%), anemia (45%) and thrombocytopenia (45%). In addition, 25 patients experienced cytokine release syndrome — grade 1 or 2 in 23 patients (70%) and grade 3 in two patients (6%) – and neurologic toxic effects occurred in 14 patients (42%) – grade 1 or 2 in 13 patients (39%). Of note, one patient had a reversible grade 4 neurologic side effect which resolved in one month, the release said.

Patients demonstrated an objective response rate of 85%, including 15 patients who experienced a complete response to treatment (45%) and one with a partial response. However, six patients with complete responses experienced a relapse in disease. All 16 patients who experienced a response to the infusion therapy did not have minimal residual disease upon evaluation.

Median progression-free survival (the time from treatment to disease worsening) was 11.8 months. Responses to bb2121 infusions occurred early, with a median time to first partial response or better of one month, and responses were durable, with a median duration of response of 10.9 months.

Lastly, the researchers noted that CAR-T cell expansion was associated with responses and CAR-T cells persisted up to one year after the infusion.

Dr. Alise Reicin, president of global clinical development for Celgene — the drug’s co-developer – noted that this trial demonstrates the promise of targeting B Cell Maturation Antigen (BCMA), which is expressed at significantly higher levels in those with multiple myeloma.

"We continue to be encouraged by the potential of bb2121 as a first-in-class BCMA-targeted CAR-T cell therapy," she said in the release. "The compelling data in these heavily pre-treated relapsed/refractory patients has provided important insights in the development of bb2121.”

The first portion of the study included a dose-escalation phase in which 21 patients received ascending doses of bb2121 to determine the maximum tolerated dose, which established the recommended dose of the phase 2 KarMMa trial. The second portion of the study was a dose expansion phase where 12 patients received bb2121 to further evaluate the safety, tolerability and clinical activity at the recommended phase 2 dose.

Study follow-up is ongoing and complete data from the additional expansion cohorts will be published at a later date.

"The data published in NEJM from CRB-401 provide the foundation for advancing the development of bb2121, which is currently being assessed in multiple clinical studies across different patient populations within multiple myeloma," Dr. Dave Davidson, chief medical officer at bluebird bio (the drug’s co-developer), said in the release. "We hope that this potentially first-in-class BCMA-targeted CAR T-cell therapy may provide a new treatment option for patients living with multiple myeloma."