Currently , Dr di Blasi said , ‘ the total hospitalisation costs for one patient receiving CAR-T therapy is approximately € 480,000 .’ Despite this , she pointed out that health economic studies have been favourable for CAR-T cell therapy , especially if the patient goes into remission and that , currently , ‘ the balance is still in favour of CAR-T cell use .’ A further limitation to wider use was that ‘ not all centres are fully certified to administer CAR-T cells ’ with currently only around 31 centres being able to provide the treatment in France . An important part of the CAR-T programme , therefore , is education and involved visiting and discussing the specific patient referral criteria with nonaccredited sites .
Q What is the safety profile of CAR-T therapy ?
A Dr di Blasi described how ‘ the two wellknown side-effects of CAR-T therapy – at least the ones that we have been concentrating on – are cytokine release syndrome and neurotoxicity syndromes , and these can vary substantially depending on the pathology being treated , the CAR-T cell product and even the different clinical trials .’ With the severity of these adverse effects graded on a scale from 1 to 5 , Dr di Blasi mentioned that ‘ grade 3 or higher [ adverse effects ] can vary from 8 % to 10 % and up to roughly 30 % for axi-cel and from 2 % to 20 % for tisa-cel . Liso-cel , for which there is currently less real-world data , also has a favourable toxicity profile .’
Nevertheless , with greater clinical experience in using CAR-T cell therapy comes a better understanding of how best to manage these adverse effects . Despite advances in the management of the two key side-effects , Dr di Blasi feels that a better understanding of other emerging adverse effects was still required . This included cytopaenia , for example , which might affect up to 10 % of patients after one year , as well as the risk of infection and hypo-gammaglobulinaemia . Finally , she revealed how there is an ongoing continuing debate over whether autologous stem cell transplantation after second-line chemotherapy is more toxic than CAR-T cell therapy . Furthermore ,
Dr di Blasi explained that the decision over whether to use CAR-T cell therapy for a patient was complex and involved a consideration of many different factors , but the existence of treatment algorithms had been of great value to clinicians .
Q How does the patient registry data compare with the outcomes seen in trials ?
A Dr di Blasi felt that the outcome data , in particular , treatment efficacy seen in realworld data derived from registry data , are comparable to that observed in the clinical trials , adding that the extent of toxicities was probably lower with the registry data , which was likely a reflection of how clinicians were
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With greater clinical experience in using CAR-T cell therapy comes a better understanding of how best to manage the adverse effects better able to manage these adverse effects in practice . Nevertheless , she stressed that because the production of products differed , it was not always easy to compare the effectiveness seen in the trials with the registry data although , broadly speaking , the two datasets provided similar results .
Q What happens if CAR-T cell therapy is not effective ?
A Dr di Blasi thinks that immunotherapy would be the next step in the management of patients who fail to respond to CAR-T cell therapy and does not believe that such patients would benefit from further chemotherapy , a point already proven in trials . She added that in some tumours , if a second surface antigen – CD20 – is still expressed , then immunotherapy can help .
Q What would you like to see in the future ?
A First and foremost , Dr di Blasi hoped to see patients with the longest possible remission and with no , or very few , long-term sideeffects . Future developments might enable a reduction in the level of side-effects through alteration of the receptor on the CAR-T cells . As she explained , ‘ we know that toxicities are partially linked to the structure of the receptor on the surface of the CAR-T cells and to the expansion profile , so modification of this structure might lead to less toxicity , and we already have three available products which have different toxicity profiles .’ While modifying the receptor might be possible , this approach is not guaranteed to lessen the incidence of adverse effects as there are many other factors that can affect an individual ’ s risk of adverse effects , including the number of T cells infused and the microenvironment of the patient ’ s tumour , both before and after infusion , and such effects are not always predictable . In addition , she added that much more work is needed to understand why some , but not all , patients are prone to cytopaenia .
Although CAR-T cell therapy targets a particular antigen , Dr di Blasi thinks that it is theoretically possible to deploy the technology in the treatment of any form of cancer ( including solid tumours ) provided that a discriminatory antigen can be found , and this is an area of ongoing research . One possible therapeutic area she would like to see CAR-T used in is in the treatment of T cell lymphomas .
Conclusion Dr di Blasi concluded that CAR-T cell therapy has been a major advance in the treatment of lymphomas , but there was still much to learn , not just about the technology itself , but also about how it affects patients and what might be achieved to maximise its benefits and minimise the adverse effects for the patients in her care .