HPE 102 – Dec 2022 | Page 9

clinicians at the hospital became more attracted to the technology , especially for patients with refractory malignancies . Given her prior experience and knowledge of allogenic bone marrow transplantation , she believed it was a natural fit , particularly as there are some complications that can arise from CAR-T cell therapy that bear similarities to those experienced by patients undergoing allogeneic bone marrow transplants . And she remains fascinated by the technology to this day .
Q How is the clinical research programme organised with your department ?
A Although her department does have strong links to the pharmaceutical industry and participates in clinical trials , an equally important part of its work involves the examination of the findings held in a national patient registry . The registry ( termed DESCAR-T ) collates data from patients across France and enables a much greater understanding of the impact of real-world experience of CAR-T cell therapy . In addition , other areas of research within the hospital include basic biological science and translational research , which are designed to better understand CAR-T .
Although diffuse large cell B lymphomas and the family of related lymphomas are treated with CAR-T cell therapy , Dr di Blasi pointed out that ‘ recently , the centre had received authorisation to treat mantle-cell lymphoma and follicular lymphoma ’.
Q How is CAR-T authorised and used in your hospital ?
A Although a novel and promising therapeutic approach , Dr di Blasi explained that CAR-T is not currently a first-line treatment option and that her hospital is only authorised to use the therapy third-line after two unsuccessful chemotherapy regimens . She mentioned how the department currently uses two CAR-T cell products aggressive B cell lymphoma or transformed follicular lymphoma . Despite the constraint of having to use CAR-T cell therapy third-line , this might change over time , and she noted that clinical trials are starting to report on the value of CAR-T cell therapy as a second-line option in either refractory patients or in those who relapse within the first year of chemotherapy .
She also added that ‘ axi-cel CAR-T cell therapy will hopefully be used as a second-line treatment for patients with lymphomas who relapse within the first year of treatment as well as refractory patients and hopefully , by the end of the year , axi-cel will be available for follicular lymphoma too .’ She revealed how the department is likewise eagerly ‘ waiting for liso-cel ( another CAR-T cell product ) to be available for large-cell B lymphoma as well as some other entities , such as transformed marginal zone lymphoma , that were not
Clinical experience means that we are now better able to identify specific risk factors ( such as high tumour burden ) that negatively affect the response to CAR-T cell therapy covered by the older CAR-T cell products .’
Although CAR-T cell therapy makes use of a patient ’ s own cells , Dr di Blasi explained that because the cells undergo modification , it is designated a ‘ product ’ and therefore subject to all the standard regulatory approvals required for drugs .
Dr di Blasi explained that in her department , after a single infusion , patients were monitored for the first 10 days and , if there are no problems , discharged home but contacted daily until day 21 . After 28 – 30 days , patients revisit the centre for efficacy assessment by a clinician . Following this , patients are reviewed after three months , as any relapse is likely to occur at this point , and then every 90 days . She described how there were no specific criteria for choosing CAR-T cell products and this relied solely on the availability (“ slot ”) of the manufacturer to produce the product . In cases where CAR-T cell therapy was ineffective , patients would not be switched to an alternative CAR-T cell product because , as Dr di Blasi clarified , ‘ one route of escaping the treatment ( that is , therapeutic failure ) is due to loss of the antigen and because the target is the same , there is little point in switching to another CAR-T product .’
Q How effective is CAR-T cell therapy in refractory lymphoma patients ?
A Dr de Blasi outlined how she has seen some remarkable results for CAR-T cell therapy , noting how ‘ we have seen complete response rates in real life that vary from 40 % to almost 60 % and are comparable to those seen in the clinical trials .’
Q Why is CAR-T cell therapy currently third line and do you ever envisage it having a wider use ?
A Dr di Blasi described how after a few years of clinical experience with CAR-T cell therapy , clinicians are now better able to identify specific risk factors , both clinical and biological ( such as high tumour burden ) that negatively affect the response to CAR-T cell therapy . Using this knowledge , she thinks that ‘ for some patients , it might be logical to conceive CAR-T cell therapy earlier in the therapeutic line .’ She mentioned that the ZUMA-12 trial ( a Phase II , multicentre , single-arm study evaluating axicabtagene ciloleucel as part of first-line treatment in patients with high-risk large B-cell lymphoma or with an insufficient response after two courses ) produced some remarkable findings . As a result , she thinks that ‘ the therapeutic strategy might change according to the clinical features at diagnosis for the patients .’ However , she felt that in practice , third-line CAR-T therapy would be best suited to those patients with limited disease who are likely to respond well to the treatment .
One important and limiting factor to the greater use of CAR-T cell therapy is cost .
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