Researchers discovered that on-site manufacturing of CAR-T cells enabled the successful production of cell therapy for almost all patients in a single-center, phase 1b/phase 2 clinical trial. Participants were being treated for acute lymphoblastic leukemia and non-Hodgkin’s lymphoma.
Orit Itzhaki, PhD, senior scientist and deputy manager of the clinical research lab at the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center, explains that when it comes to commercial CAR-T cell products there are numerous obstacles to success, such as high costs and a long turnaround time from leukapheresis to infusion.
“In-house production of CAR T-cells can overcome most of these obstacles, leading to a rising number of clinical centers generating their own CAR-T products today,” Itzhaki and her colleagues added.
The phase 1b/phase 2 trial evaluated an anti-CD19 CAR-T cell therapy produced on-site at Sheba for patients with B-cell malignancies. A comprehensive analysis was performed of the manufacturing process of 91 CAR-T therapies produced at Sheba for patients 50 years old or younger with relapsed or refractory ALL and non-Hodgkin’s lymphoma (NHL).
Between June 2016 and August 2019, 93 intensely treated patients who suffer from relapsed or refractory B-cell malignancies received treatment with in-house CAR-T cell therapies at Sheba. 37 of the patients had relapsed or refractory ALL, and 53 had relapsed or refractory NHL. All of the patients underwent lymphodepletion 2-4 days before infusion, which was followed by a CAR-T cell infusion of 1 × 106 cells/kg.
Follow-up assessments were conducted 1-2 months after infusion, and the trial’s primary endpoints considered the feasibility of CAR T-cell production, patient safety, and overall response rate (ORR). In sum, the analysis demonstrated:
- ORR of 84% (n = 30 of 36) for patients with ALL and an ORR of 62% (n = 35 of 52) for NHL
- 67% of patients with ALL achieved a minimal residual disease (MRD)-negative complete response to therapy
- 17% had an MRD-positive complete response
- 14% had disease progression
- 16 patients with NHL experienced complete response to therapy, 16 had partial response, and 20 (38%) had disease progression
In the past decade, the development of innovative, potentially life-saving, gene-modified therapies for oncologic patients has appeared prominently in the field of cancer treatments. CAR-T cell therapy is one of the most significant advances, demonstrating the impressive ability of these types of therapies to treat patients with ALL and diffuse large B-cell lymphoma. However, the high costs of acquiring commercial CAR-T cell products, as well as complex logistics and long turnaround times, have unfortunately led to limited patient access.
Itzhaki and colleagues evaluated the efficacy of the on-site production of CAR-T cell therapy and tumor-infiltrating lymphocyte (TIL) products for 93 patients with relapsed or refractory B-cell ALL and non-Hodgkin lymphoma. This pretreated population group received CAR-T cell products that had a product turnaround time of 9 to 10 days (compared to 1 to 2 months for commercial products), and all products satisfied the criteria for cell viability, sterility, and mycoplasma and endotoxin testing.
The results of Itzhaki’s study show strong support for a point-of-care manufacturing model for gene-modified cellular products, which have incredible potential as an effective method for administering lifesaving cancer treatments. The hope is that an increasing number of patients with more types of cancer will eventually be able to benefit from effective CAR-T cell therapeutics.