Newly-Approved Ide-Cel Becomes Available for Treatment at SCCA

David Maloney, MD, PhD

Idecabtagene vicleucel (ide-cel; formerly bb2121; Abecma) is now an available treatment option for oncologists treating some patients with relapsed or refractory multiple myeloma at Seattle Cancer Care Alliance (SCCA), the only National Comprehensive Cancer Network designated cancer center in the state of Washington, according to a press release issued by SCCA.¹

Ide-cel was granted approval by the FDA in March for the treatment of adult patients with relapsed or refractory multiple myeloma after 4 or more prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody. It was the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy to be approved by the FDA.^1,2

“The FDA approval of this novel therapy is a significant milestone in the advancement of new, innovative therapies for multiple myeloma,” said David Maloney, MD, PhD, medical director for cellular immunotherapy at the Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance, in the press release. “We are excited about the continued expansion of CAR T-cell treatment options available to our patients, and the potential ide-cel offers to extend the lives of those who have multiple myeloma.”

Data from the pivotal phase 2 KarMMa trial (NCT03361748) supported the FDA’s decision to grant approval. In the study, ide-cel achieved deep and durable responses in patients with heavily pretreated multiple myeloma, including in the subgroups of patients who were treated with 4 or more prior lines of therapy or were triple-class refractory.²

BCMA CAR T cells were administered to the study patients at a 1 of 3 dose levels including: 150 x 10⁶ (n = 4), 300 × 10⁶ (n = 70), or 450 × 10⁶ (n = 54) CAR-positive T cells after patients were received lymphodepleting chemotherapy of fludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day). The study investigated overall response rate (ORR) as its primary end point. Achievement of a complete response (CR) rate or better, time to response, duration of response, progression-free survival, minimal residual disease, safety, pharmacokinetics, and immunogenicity were the secondary end points.

A total of 128 patients were dosed with CAR T cells in the study. Of those who were evaluable for response, the data shows an ORR of 72% (95% CI, 62%-81%) with ide-cel, which included stringent CRs (sCR) in 28% (95% CI, 19%-38%). The median time to response was 30 days (range, 15-88) and responses were durable. The median DOR was 11 months (95% CI: 10.3-11.4) among all responder and the median DOR was 19 months (95% CI, 11.4 to not evaluable) among those who achieved a sCR. For 65% (95% CI: 42%-81%) of patients who achieved an sCR, remission lasted for 12 months or more.

The safety profile of ide-cel showed a low incidence of cytokine release syndrome (CRS). Any-grade CRS occurred in 85% of patients overall with grade 3 CRS occurring in 9%. There was also a small percentage of patients (0.8%) who experienced grade 5 CRS. The median time to CRS on-set in the study was 1 day (range, 1-23). CRS typically lasted in these patients for a median of 7 days (range, 1-63).

Ide-cel also showed a low occurrence of neurotoxicity in the study at 28%, and 4% for grade 3 events.

Overall, the most common non-laboratory adverse events observed with ide-cel in KarMMa were CRS, infections, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.

Ide-cel will not be the first that hematologist/oncologists at SCCA have experienced with BCMA CAR T cells. The organization has previously administered this therapy to patients by way of clinical trials and it is merely being re-introduced in the clinic.¹

“Our clinical trials at the SCCA have provided us with extensive experience using BCMA CAR T cells for multiple myeloma. The new FDA approval allows our to leverage this knowledge and safely bring a promising therapy to a wider population of adult patients with multiple myeloma,” said Damian Green, MD, Seattle Cancer Care Alliance, and Associate Professor, and who leads translational myeloma research programs at Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center, in a statement.

“We are pleased to offer this new advanced therapy to patients who are suffering from relapsed or refractory multiple myeloma,” said Nancy Davidson, MD, president, and executive director of Seattle Cancer Care Alliance. “We are committed to delivering personalized care to our patients and improving patient outcomes and excited to be among the first cancer centers in the nation to offer this treatment to adult patients with multiple myeloma.”

_References:

_{1. Seattle Cancer Care Alliance is an authorized treatment center for ide-cel CAR t-cell therapy. News release. Seattle Cancer Care Alliance. May 13, 2021. Accessed May 25, 2021. https://bit.ly/34kFkuh}

_{2. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the First Anti-BCMA CAR T Cell Therapy for Relapsed or Refractory Multiple Myeloma. News release. Bristol Myers Squibb. March 26, 2021. Accessed March 27, 2021. https://bit.ly/3m0V915}