ICER Seeks Public Comment on Scoping Document for CAR-T Treatments

The Institute for Clinical and Economic Review (ICER) has released a draft version of their scoping document that will compare the clinical effectiveness and value of 2 chimeric antigen receptor (CAR)-T cell treatments being reviewed by the FDA: tisagenlecleucel-t (CTL-019 from Novartis) and axicabtagene ciloleucel (KTE-019 from Kite Pharma).

CAR-T cells are being considered the next frontier of cell-based immunotherapy to move from the bench to the bedside. By modifying a patient’s own T cells, CAR-T treatments transduce the patient’s T cells to express a cell surface receptor that can help boost the body’s immune response against specific cancer cells. In the case of B-cell leukemias—targets of the 2 treatments listed above—the T cells are generated to target the CD19 antigen expressed on B cells.

CTL-019—the result of a partnership between Novartis and the University of Pennsylvania—recently received unanimous approval (10-0) from FDA’s Oncologic Drugs Advisory Committee for the treatment of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). CAR-T cell treatments are riddled with significant adverse effects, and CTL-019 is no exception: cytokine release syndrome (CRS) and neurological toxicity are a major concern. KTE-C19 treatment, indicated for B-cell non-Hodgkin lymphoma (NHL), also presents with CRS.

ICER’s scoping document acknowledges the clinical options presented by CAR-T therapy, but questions the durability of the effects, management of adverse effects, such as CRS, and the high cost of this very personalized treatment.

The analysis will use the National Comprehensive Cancer Network (NCCN) Guidelines to choose comparator treatments for CAR-T in relapsed/refractory B-ALL, namely clofarabine, tyrosine kinase inhibitor-based chemotherapy, or blinatumomab. For B-cell NHL, CAR-T therapy will be compared with salvage chemotherapy treatments or second-line treatments recommended by NCCN such as gemcitabine, dexamethasone, and cisplatin. The primary outcome of interest is overall survival (OS).

ICER plans to use a decision analytic model to assess the cost effectiveness of CTL-019 and KTL-C19, relative to the chosen comparators that have clinical and economic evidence available. Patient populations to be included in the analysis will be:

• Pediatric and young adult patients with relapsed/refractory B-ALL (CTL019, Novartis)
• Adults ages 18 years and older with relapsed/refractory aggressive B-cell lymphoma (KTE-C19, Kite Pharma).

ICER plans to evaluate each intervention in terms of the proportion of responders over 3-months post transfusion. Life years and quality-adjusted life years gained will be evaluated, along with infusion costs, treatment acquisition, administration and monitoring, adverse events, and other healthcare utilization.

The scoping document, in its current form, was developed with input from several patient advocacy organizations, several specialty societies, practicing hematologists and oncologists, payers, and pharmaceutical manufacturers. According to ICER, patients expressed hope that CAR-T therapy would be less toxic than traditional chemotherapy and stem cell transplant, and improve patient quality of life. Clinicians urged ICER to focus on progression-free survival and OS while acknowledging the challenges in doing so given the limited numbers of patients treated and the short duration of follow-up.

The document is now open for public comment until August 29; input received up to that date will inform a subsequent revised document to be posted in the second week of September.