by François Boissier
PARIS, 15 June (APM) - CAR-Ts, the new cancer immunotherapies based on genetically modified T cells modified to target tumours, still raise many questions, say the authors of a French national cancer institute (INCa) report on immunotherapies.
essentially covers specific checkpoint inhibitor immunotherapies (APMHE 58523
) but also takes a look at CAR-Ts.
Two products have recently been authorised in the U.S., on the basis of “open label non-comparative Phase II trials”. INCa says they are expected to be launched in France “in 2018”.
However “many questions persist around these innovative products whose price is likely to be very high ($475,000 in the U.S. for Kymriah - [Novartis’s tisagenlecleucel] and $373,000 for Yescarta [Gilead’s axicabtagen ciloleucel]), particularly in terms of target population and treatment hierarchy.”
INCa notes that among the many clinical trials of CAR-Ts (189 listed in mid-2017), most concern products targeting antigen CD19, but a total of 34 different targets are being studied. Moreover, while the initial studies only concern haematological cancers, trials are now under way in solid tumours.
A specific characteristic of CAR-Ts is that 40% of trials concern paediatric populations, the report authors say.
These treatments present specific challenges concerning appropriate use, linked both to their individualised nature (the patient’s own cells are modified and reinjected) and to their status as genetically modified organisms, which “necessitates long term follow-up of treated patients”.
There are therapeutic strategy challenges in “defining eligible patient profiles and positioning of CAR-T cells compared to existing therapies, especially haematopoietic stem cell transplants”. For the moment, with only non-comparative studies available, this is difficult.
There are also challenges related to safe use, with the need to train professionals to look out for possible complications, and the issue of real world follow-up. There is a need to set up a comprehensive registry to monitor patients at the national and European levels.
Specific organisational challenges
CAR-Ts also present “specific organisational challenges” which are different from those of other immunotherapies. These products “are different from other cancer drugs due to their production methods” which “require specific skills within hospitals”.
The following all need to work closely together: “clinical haematology services, the apheresis service, the cell therapy unit and the hospital pharmacy [CAR-Ts have drug status and “reception, defrosting and dispensing all fall under the responsibility of the hospital pharmacy"], along with the intensive care unit, where required”.
“In view of the specific nature of these products (cell therapy products) the question arises of which centres will have the necessary skills to treat patients.”
As for the economic challenges, there are “many new questions as to the real cost of such treatments,” since beyond the very high prices of the first treatments authorised in the U.S., “the complex circuit of a medicine derived from individualised production based on the patient’s own lymphocytes” and the “ensuing care pathway” must also be taken into account.
In the U.S., “performance contracts” based on treatment response have been drawn up for the payment of these treatments. “France is pondering the relevance and feasibility of such contracts, whose success depends on comprehensive registries, accurate choice of performance criteria and shared interpretation of results,” INCa said.
“CAR-T cells carry hope of cure in some haematological malignancies with poor prognosis, and notably in paediatrics. But in the near future, equal access could clash with their impact on spending”.