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EHA 2021 | Outcomes of children under 3 treated with tisagenlecleucel for B-ALL

Sara Ghorashian, PhD, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, discusses the findings of a retrospective analysis of the outcomes of children under three treated with tisagenlecleucel for B-cell acute lymphoblastic leukemia (B-ALL). Dr Ghorashian discusses the rationale for the study, and reports that manufacturing had good feasibility, with only a 7% manufacturing failure rate, and that the complete response rate/complete response with incomplete hematologic recovery rate at day 28, as determined by measurable residual disease (MRD)-negativity, was 92% versus 77% in the ELIANA study (NCT02435849). The toxicity profile was also similar; thus, these results support the use of tisagenlecleucel for B-ALL in this patient subgroup. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.

Transcript (edited for clarity)

Thanks for inviting me to speak on the outcomes of the younger patients treated with tisagenlecleucel. It’s important to identify these outcomes because on the ELIANA study, which was a pivotal study for the use of tisagenlecleucel, excluded patients aged under three, and with B-ALL.

So, to date, the outcomes of these patients, aren’t known. These are often patients with multiple relapses of infant ALL, a disease entity which is known to have historically, very poor outcomes with standard chemotherapeutic approaches, for dealing in the context of stem cell transplantation...

Thanks for inviting me to speak on the outcomes of the younger patients treated with tisagenlecleucel. It’s important to identify these outcomes because on the ELIANA study, which was a pivotal study for the use of tisagenlecleucel, excluded patients aged under three, and with B-ALL.

So, to date, the outcomes of these patients, aren’t known. These are often patients with multiple relapses of infant ALL, a disease entity which is known to have historically, very poor outcomes with standard chemotherapeutic approaches, for dealing in the context of stem cell transplantation. So, they represent an area of unmet clinical need and therefore their outcomes are very important to identify.

So, through the IBFM Resistant Diseases Committee, we identified centers that had been able to proceed to give this treatment to children aged under three at screening, and we asked them to submit data on a retrospective basis, using a standardized data collection form, in order to identify the outcomes. This is very important, because what we know is that some centers in Europe, are not, don’t have access to tisagen for patients aged under three, and so the ability to define these outcomes might be of importance in improving access for this very important patient group.

And what we found as a result of our analysis was that there was a good feasibility of manufacturing. Traditionally, there’s been some concern that you may not be able to manufacture a product from a patient who’s in an infant age range. But in fact, we demonstrated that there was only a 7% manufacturing failure rates, and only one out of 30 patients that we’ve collected data on progressed through the early phase of treatment and was not able to go on to receive a CAR T-cell product.

So, in terms of the outcomes then, and compared to the patients in the ELIANA study, who were aged above three years, we documented a very similar, complete response or complete response with incomplete hematological recovery at day 28. And we had an MRD-negative rates of 92% versus 77% on the ELIANA Study and indeed our event-free survival and our overall survival outcome data were very similar to patients of an older age range receiving treatment on the ELIANA study. So, for example, the six-month event-free survival was 67 versus 73%. And the 12-month event-free survival was 58 compared to 50% on the ELIANA study. And the overall survival data are also very closely matched both at six and 12 months.

We also documented that the toxicity profile was very favorable for the delivery of tisagen to this age range, if anything, mirroring the real-world data, in the older age group, we identified that there was overall, a reduced rate of severe cytokine release syndrome. Although we used a slightly different grading system for the documentation of cytokine release syndrome, we were able to corroborate that there was a reduced rate of severe CRS by looking at other measures, such as median duration of CRS and the median duration of ICU stay and the frequency of tocilizumab therapy. We also documented a reduced rate of severe neurotoxicity as well.

So overall, this is a therapy which is feasible to deliver to the younger child. The outcomes in terms of disease response are very similar and the longer-term outcome data are very similar. Although, the meeting follow-up is reasonably short and longer follow-up would be required.

And so, this provides a very important platform potentially, particularly with longer follow-up, to considering whether this approach can be supported through an increased access for these younger children to tisagenlecleucel.

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Disclosures

Sara Ghorashian, PhD, has received honoraria from Novartis.