BCMA Bispecific Antibody “Promising” for Relapsed or Refractory Myeloma

Interim results from a phase I dose-finding study suggest that CC-93269, a bispecific antibody that binds B-cell maturation antigen (BCMA) on malignant plasma cells and CD3 on T cells, is active in patients with relapsed or refractory multiple myeloma. However, treatment-related adverse events (AEs) were common, with more than three-quarters of patients experiencing cytokine release syndrome (CRS).

These findings were presented at EHA25 Virtual, the remotely held 25th European Hematology Association Annual Congress, by Luciano J. Costa, MD, of University of Alabama at Birmingham.

The study enrolled 30 adults who had received at least 3 prior therapies for myeloma, but no prior BCMA-directed therapy, and whose disease had progressed within 60 days of last treatment.

CC-93269 was administered intravenously at doses ranging from 0.15 to 10 mg over 2 hours on days 1, 8, 15, and 22 for cycles 1 to 3; days 1 and 15 for cycles 4 to 6; and day 1 for cycle 7 and beyond. Patients received fixed doses during stage 1 of the study; in stage 2, patients received a first fixed dose of CC-93269, followed by intrapatient escalating doses starting on day 8 of cycle 1. Per study protocol, treatment could be given for up to 2 years.

Dr. Costa described the patient population as heavily pretreated, with a median of 5 prior therapies (range = 3-13). The median age of patients was 64 years (range = 42-78). Approximately one-third of patients (n=9) had high-risk cytogenetics.

Patients received a median of 3.5 treatment cycles. All but 1 patient experienced a treatment-related AE, and nearly three-quarters (n=22; 73%) experienced a grade 3/4 AE. The most common grade ≥3 hematologic AEs included:

  • neutropenia (43%)
  • anemia (37%)
  • thrombocytopenia (17%)

Other frequently reported grade ≥3 AEs included infections (30%) and diarrhea (3%).

Although study protocol required CRS prophylaxis with dexamethasone be given at the first CC-93269 dose, with dose increases in patients receiving 6 mg or more, 23 patients (77%) experienced CRS. Most cases of CRS were grades 1 or 2 and occurred after the first dose and in patients receiving CC-93269 at 6 mg or higher, Dr. Costa noted.

Four patient deaths were reported. One patient receiving CC-93269 6 mg as first dose and 10 mg on day 8 of cycle 1 developed CRS and died; contributing factors were rapid myeloma progression with extensive extramedullary disease and concomitant infection. The other 3 deaths were considered unrelated to CC-93269 treatment.

In the preliminary efficacy analysis, the researchers reported an overall response rate of 43%, with 13 patients achieving a partial response or better, including 5 (17%) who achieved complete response or stringent complete response. In addition, 92% of responders achieved minimal residual disease negativity in the bone marrow on or before day 1 of cycle 4.

All responses occurred in the higher-dose groups (>3 mg) and there appeared to be a dose-response relationship, the investigators observed. Among the 9 patients who were given the CC-93269 10 mg dose, the overall response rate was 89%, including 44% complete response or stringent complete response.

As the data cutoff, 11 of the 13 responses were ongoing, with a duration of response ranging from 5.3 to 40.6 weeks.

“These early data show remarkable activity in highly refractory, heavily pretreated patients with multiple myeloma,” Dr. Costa said, adding that the recommended phase II dose has not yet been reached.

While the study investigators called these findings “promising,” they are limited by the small patient population and lack of a comparator arm.

The authors report relationships with Celgene, which sponsored the trial.


Costa L, Wong SW, Bermudez A, et al. Interim results from the first phase 1 clinical study of the B-cell maturation antigen (BCMA) 2+1 T cell engager (TCE) CC-93269 in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Abstract S205. Presented as part of EHA25 Virtual, June 12, 2020.