Gene Therapy in Community Practices—Administering CAR T Therapies

While immune-based treatments have gained significant strides in cancer care, chimeric antigen receptor (CAR)-T cells have also started to make their mark. With 2 treatments approved so far for liquid cancers, the extent of remission has surprised the field.

However, the treatments are not easy to administer and the adverse effects can prove extremely challenging—for the caregivers, patients, and families. So how are community practices coping with administering CAR-T treatments? At the 2018 Community Oncology Conference hosted by the Community Oncology Alliance, Houston Holmes, MD, MBA, FACP, Texas Oncology, shared his experience with administering CAR T-cells in a community cancer center—based setting.

Holmes started the discussion with an overview of the recently published study for the first treatment that was approved in August last year: Novartis’ tisagenlecleucel (Kymriah).

The first-ever case report with these CD19-specific CAR-T cells was published back in 2013,¹ Holmes said, and described the results of CAR T administration in 2 children with relapsed and refractory pre—B-cell acute lymphoblastic leukemia (ALL). While the T-cells proliferated and persisted in the cerebrospinal fluid for 6 months, significant grade 3 or 4 adverse events were noted in the patients, including cytokine release syndrome (CRS) and B-cell aplasia.

Holmes said that 1 of the patients remained in complete remission (CR) at 11 months, but the second child had a relapse about 2 months following treatment, likely due to the absence of CD19-expressing blast cells.

Holmes then presented long-term results from the same trial that were recently published,² following a 25-center global phase study in pediatric and young adult patients with B-cell ALL. The results were very encouraging, according to Holmes, with an 81% overall remission rate at 3 months, following a single infusion of tisagenlecleucel. The CAR-T cells persisted in these patients and the authors reported an overall survival of 76% (95% CI, 63 to 86) at 12 months.

Holmes pointed out that the median duration of persistence of tisagenlecleucel in these patients was 168 days in the blood (range, 20 to 617 days).

There is a reason, however, that CAR T-cell therapy was designated the breakthrough of the year by the American Society of Clinical Oncology, Holmes told the audience.

However, 77% of patients experienced CRS and about 50% were treated with tocilizumab, he said. Neurologic events were manageable as well, and occurred in 40% of patients.

“The patients did fine initially, but then crashed,” Holmes said, “with fever, high cytokine levels, and high white blood cell count.”

Toxicities are very common with this adoptive cell therapy, he said, “which can be very distressing for patients and their families.” Supportive care, he said, is a typical management strategy for these adverse effects.

From a community clinic’s perspective, administering these treatments to patients or participation in clinical trials to test these treatments, is feasible, Holmes said. “However, practices will need facilities that have the capacity for apheresis. Additionally, the program requires a team effort, with participation of the pharmacy, toxicity management, nursing services, social work, and consultant support,” including critical care, neurology, cardiology, and an emergency department.

Additionally, the clinic will need to establish a Risk Evaluation and Mitigation Strategy.

“All of this can certainly be achieved in the community setting,” Holmes assured the caregivers representing community practices who were in attendance.

Holmes then brought up the elephant in the room: the cost of this treatment. There’s been significant debate over whether the treatments are cost effective at $373,000 (Kite Pharma’s Yescarta) and $475,000 (Kymriah).

“All major payers have approved these treatment,” Holmes said. Payers like Optum, Aetna, and Cigna, are accessing Transplant Network agreements for this treatment, he said. “Our experience has been that you have to deal with payers on a case-by-case basis,” he added.

The Institute for Clinical and Economic Review (ICER) released a report based on their analysis of these treatments earlier this year. According to ICER, the cost of both treatments aligns with their clinical value.

References

1. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor—modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509-1518. doi: 10.1056/NEJMoa1215134.
2. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-448. doi: 10.1056/NEJMoa1709866.