Amer Beitinjaneh, MD, University of Miami, Jackson Memorial Hospital, Miami, FL, shares the updated results of the Phase III ALLELE study (NCT03394365) of tabelecleucel (tab-cel) for patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) following allogeneic stem cell transplant (alloSCT) or solid organ transplant after rituximab failure. Prof. Beitinjaneh describes the characteristics of the patients included in this study and outlines the findings from the study, which indicated that tab-cel leads to high and durable responses. In addition, overall survival (OS) was higher in responders versus non-responders, and there were no safety concerns associated with tab-cel treatment. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT™ and CIBMTR® held in Orlando, FL.
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Transcript (edited for clarity)
So we had the pleasure this year to attend the American Transplantation Cell Therapy Meetings, Tandem ’23, and we presented the updated result of the Phase III study. It’s a multicenter, open-label, single-arm study about tab-cel, which is an off-the-shelf product, EBV-positive CTL in the treatment of EBV-positive post-transplant lymphoproliferative disorders, or PTLD, in the setting of allogenic transplantation or solid organ transplantation, which I’m going to refer to ALO, and I’m going to refer to SOT, for patients who have failed prior rituximab based therapy...
So we had the pleasure this year to attend the American Transplantation Cell Therapy Meetings, Tandem ’23, and we presented the updated result of the Phase III study. It’s a multicenter, open-label, single-arm study about tab-cel, which is an off-the-shelf product, EBV-positive CTL in the treatment of EBV-positive post-transplant lymphoproliferative disorders, or PTLD, in the setting of allogenic transplantation or solid organ transplantation, which I’m going to refer to ALO, and I’m going to refer to SOT, for patients who have failed prior rituximab based therapy. So we presented the most updated results of that study.
So as just a big quick background, the EBV-positive PTLD, once they failed rituximab based therapy, their outcomes are very poor. In the range of less than six month overall survival once they failed rituximab based therapy. So that’s why the study was designed for those population who don’t have any approved treatments.
The study was designed in two cohorts. A cohort of allogeneic transplantation, a cohort of solid organ transplantation, who developed PTLD. Patients will receive an outpatient infusion on day one, day eight, day 15, followed by two weeks of observation. And then they will have a restaging scan to assess response. Each dose, it’s about 2 million per kilogram of those tab-cels. And we enrolled and analyzed by November 2021. That was a cutoff for analysis. We have 43 patients. 14 being in allogeneic PTLD, and 29 in SOT PTLD, so a total of 43 patients. And the goal eventually is to enroll 66 patients total.
So among those patients, majority were predominantly white. Median age was 48, and they compromised very high risk PTLD patients. Most of the patients had high or intermediate PTLD adopted risk score. 76% had an external disease, lymphoma. Most of them had a diffuse large B-cell type lymphoma. Some have lymphoblastic lymphoma as well.
And we have from SOT standpoint, different organ transplants. Most commonly was kidney, but there was kidney, heart, lungs, and liver, and multiorgan transplants. Among those patients, PTLD on median was diagnosed about four months from the allogeneic transplantations. About one year from SOT transplantation. Patients received the treatment on the study in an average of 1.2 months for the allogeneic patients. Took longer for patient on SOT to receive the therapy. Took about an average 6.6 months to receive the infusion. Median cycles required was two cycles. The cycles being one month.
And when we look at response, which was exciting to report, overall response was 51.2% of a response. And CR, so complete response among those were 27.9%. And if we look for allogeneic PTLD, the complete response were 42.9%. So pretty high response rates. And interestingly enough, our durable responses, even for patients who achieved partial response. So our median duration response was 23 months. And to achieve a response was pretty quick. Median time to response was one month. So one cycle, we achieved the response. So those responses we’re excited to report. And we need to report the overall survival, which again was as a whole group, or median overall response, exceeded 14 months. 18.2 months total. And for patients who responded to treatment, they have one year overall survivals of 84%. Compared to people did not respond, they have only 34% one year overall survival. So the survivals was different between those two – patients who respond or who did not respond, which is important to report.
And lastly, the study looked for not only efficacy, but also the safety. So the treatment was very safe. There was no report any deaths related to the treatment. There was five deaths on the study. Three of them were for disease progression. There were only two patients who had grade three adverse events, and they both were reversible. And to our surprise, there was no report of tumor flare reactions. Tumor flare reactions is something that was reported in the past when those T-cells attacked the lymphoma you see there’d be sometimes local expansions. That was not reported. And interestingly enough, there was no cytokine release syndrome. There was no infusion reactions, there was no infection related to the infusion itself. And there were no organ failures or graft-versus-host disease associated with the therapy. So it was so far pretty safe. And we continue to report efficacy and safety on this product. But overall, we felt that the results suggest this treatment can be transformative for those patients who has no other options at the moment.