Part 1: Capturing essential information on the manufactured medicinal product
As of February 2020, only two CAR-T cells have been approved by the European Medicines Agency (EMA):
- tisagenlecleucel (Kymriah®) is approved for the treatment of children and young adults with relapsed/ refractory B-cell acute lymphoblastic leukemia (ALL) and for the treatment of patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL)
- axicabtagene ciloleucel (Yescarta®) is approved for the treatment of patients with relapsed/refractory B-cell NHL
Capturing immediate and delayed information on patients with approved CAR-T cells is mandated by the Marketing Approval terms and of utmost interest to many interested parties in the field. EBMT is partnering with Manufacturing Authorization Holders (MAH, Pharmaceutical companies that market CAR-T Cells) to conduct Post-Authorization Safety Studies (PASS).
As a consequence of these obligation and agreement, centers are expected to report on all commercial Kymriah® and Yescarta® products administered after EMA issued the Marketing Approval in August 2018; this includes retrospective registration and data entry for all patients treated with Kymriah before agreements were in place between EBMT and Pharma, and before your center started to report on cellular therapies.
We will regularly provide you with practical guidance on how to fill the important information on medicinal products and treated patients. In this first publication, we focus on data entry that describe the manufactured medicinal product, listing fields as they currently appear in Promise, and expected entries.
When a patient is treated at your center, please register with the EBMT registry as soon as the hospital pharmacy emits the purchase order or at the latest when the patient undergoes apheresis in order to procure the starting material to the manufacturer. This provides the opportunity to evaluate the proportion of patients who will NOT receive the treatment while indicated, and the reasons for this failure (“Intent-to-treat” or ITT analyses).
When the patient has received the treatment, please timely complete the following information:
- Since both products are “commercial” please answer “Institutional guidelines / standard treatment” to the Clinical Setting question
- In the “Cell Infusion Unit” section, please enter the following information:
- Name of the manufacturing facility (Novartis or Kite/Gilead), Name of the (CIU) package (Kymriah® or Yescarta®)
- The single most important information is the batch number, that will allow to retrieve additional information from the manufacturer in the context of PASS: so please, pay extreme attention when entering this information
- All following information regarding product composition is therefore dispensable,:
- In the “Cell infusion episode” section, there is a subsection on infused cell dose. Completing this information is dispensable for commercial products, since it can be retrieved using the batch number (see above). For your information:
- Kite/Gilead does not currently provide the actual information on the exact dose contained in each personalized Yescarta® product. The product meets a pre-specified range of values (0.4 – 2 x 108 cells, as per Summary of Product Characteristics, SmPC), so please do not enter any value
- Novartis provides a Certificate of Analysis with each Kymriah®product that contains information on total nucleated cells, CAR-T cells, viability and more. In the question “Number of CD3+ lymphocytes” it is possible but unnecessary to enter the calculated dose of “CAR-positive viable CAR-T cells” that appears in the “Quantity” section of this document.
The EBMT community thanks you for your contribution to progresses in this innovative field.
CAR-T cells activities in Europe