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BSH 2022 | The treatment and management of PTLD

In this video, Sridhar Chaganti, MD, PhD, MRCP, FRCPath, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, discusses the management and treatment of post-transplant lymphoproliferative disease (PTLD). Dr Chaganti first gives an overview of PTLD, and further discusses first line therapy for patients with PTLD after solid organ transplant with rituximab. Dr Chaganti then discusses treatment options for patients with relapsed/refractory (R/R) disease, as well as unmet needs in this area. To conclude, Dr Chaganti discusses treatment options for patients with Epstein-Barr virus positive (EBV+) PTLD with cytotoxic T lymphocytes, and highlights the ongoing ALLELE trial (NCT03394365) investigating the use of tabelecleucel for the treatment of EBV+ PTLD. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.

Transcript (edited for clarity)

So in terms of post-transplant lymphoproliferative diseases, majority of patients we see are either polymorphic histology, or they will have monoclonal lymphomas, predominantly diffuse large B-cell lymphoma. So the first-line therapy for many of these patients who have PTLD arising after solid organ transplant these days is using a risk stratified sequential treatment approach, RSST as we call it...

So in terms of post-transplant lymphoproliferative diseases, majority of patients we see are either polymorphic histology, or they will have monoclonal lymphomas, predominantly diffuse large B-cell lymphoma. So the first-line therapy for many of these patients who have PTLD arising after solid organ transplant these days is using a risk stratified sequential treatment approach, RSST as we call it. So we give four doses of rituximab for all patients and then assess response. And if patients have a good response and a low baseline IPI, they will continue with four further doses of rituximab and avoid chemotherapy altogether. So this is a strategy that is applied to roughly around a third of patients will avoid chemotherapy in this setting. The other two thirds will either not have a good enough response or will have a higher baseline IPI and will then move on to receive R-CHOP chemotherapy.

With this strategy, the overall response rates at the end of treatment are around 80 to 90%. Around 60 to 70% of patients will have a CR. And we know that the median survival using this strategy is now in excess of six years. Unfortunately, for patients who relapse or have refractory disease, second-line and beyond treatment options are very limited because treatment toxicity is quite high. So higher intensity chemotherapy, autologous stem cell transplant comes with serious toxicity in this patient group. And currently it is an area of unmet need. But for patients who have EBV positive PTLD, which is roughly around 50% of all PTLD patients, we do have the option of using cytotoxic T lymphocytes. So these are EBV targeting cytotoxic T lymphocytes. And in this context, we currently have a clinical trial open and available in the country, and it is running at University Hospitals, Birmingham. It is called the ALLELE trial, which uses third party donor-derived EBV CTLs for this group of patients.

And the data that we have on EBV CTL therapy for relapsed/refractory PTLD is roughly around 50% of patients will have a long-term benefit, which is a lot better than what is without this treatment. And there is still a significant unmet need for EBV negative PTLD, where we need new treatments.

 

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