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1016 Intention to Treat Analysis of Real-World Outcomes Following Tisgenlecleucel Therapy for Pediatric and Young Adult ALL through a National Access Programme

Program: Oral and Poster Abstracts
Session: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
Biological, CAR-Ts, Therapies, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Sara Ghorashian, FRCPath, PhD1, Caroline Furness2*, Michelle Cummins3*, John A Snowden, BSc (Hons), MBChB, MD, FRCP, FRCPath4, Maeve A O'Reilly, MBBCHBAO5, Claire Roddie, PhD, MD6*, Lorna Neill7*, Emma Nicholson8*, Caroline Besley, MBBChir, MRCPath, MRCP9*, Sridhar Chaganti, MD, PhD, MRCP, FRCPath10*, John Gillson, MD11*, Antonio Pagliuca, MBBS, MA, FRCP, FRCPath12, Anna Castleton, FRCPath13*, Amit Patel, MBBS, PhD, FRCPath, MRCP14, Peter Clark, MA MD FRCP15*, Robert Fernley15*, Robert Wynn, MD16, Ajay Vora, MD17, David I. Marks, MB, MS, FRACP, PhD, FRCPath18, Geoff Shenton19*, Persis J Amrolia, FRCP, FRCPath, PhD20*, Denise Bonney21* and Rachael E Hough, MD22*

1Developmental Biology and Cancer, UCL Great Ormond Street Institute of Child Health, London, ENG, United Kingdom
2Haemato-Oncology, Royal Marsden NHS Foundation Trust, London, United Kingdom
4Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom
5Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
6UCL Cancer Institute, London, United Kingdom
7Department of Haematology, University College London Hospitals NHS Foundation Trust, London, ENG, United Kingdom
8Department of Haematology/ Bone marrow transplantation, The Royal Marsden NHS Foundation Trust, London, United Kingdom
9Haematology/BMT, University Hospitals Bristol, Bristol, United Kingdom
10Centre for Clinical Haematology, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom
11Department of Haematology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
12Haematological Medicine, King's College Hospital NHS Foundation Trust, London, United Kingdom
13Haematology, The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom
14Haematology and Transplant Unit, The Christie Hospital, Manchester, United Kingdom
15NHS England and NHS Improvement, Redditch, United Kingdom
16Dept. of Blood and Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, United Kingdom
17Great Ormond Hospital, London, United Kingdom
18University Hospitals Bristol and Weston NHS Foundation Trust, Professor of Haematology and Stem Cell Transplantation University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
19Newcastle Hospitals NHS Foundation, Newcastle upon Tyne, United Kingdom
20Bone Marrow Transplantation Department, Great Ormond Street hospital NHS Trust, London, United Kingdom
21Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom
22Haematology, UCLH, London, United Kingdom


Tisagenlecleucel was approved in Europe for relapsed/refractory acute lymphoblastic leukemia (ALL) in young patients in 2018. In England, a national CAR T cell panel (NCCP ALL) ensures equity of access and assesses eligibility using inclusion and exclusion criteria based on the ELIANA study. All UK cases are discussed. Eligible cases are allocated to one of 9 JACIE-FACT IEC-approved centres based on age-appropriate service, capacity, distance and patient preference. We systematically reviewed all cases from panel inception providing an opportunity to analyse complete real-world ALL outcomes from this national access programme for tisagenlecleucel on an intention-to-treat (ITT) basis.


We included all patients discussed in the NCCP ALL from Nov 2018 up to July 16th 2020. Clinical data were retrospectively reported in a standardised dataset to allow central analysis of disease and toxicity-related outcomes. Survival outcomes were assessed as for other CAR studies, using Kaplan-Meier estimates of survival from infusion. These included overall survival (interval to death from any cause) and event-free survival as defined in the ELIANA study (interval to death, disease relapse, or treatment failure defined in turn as failure to respond by day 30, with patients receiving further therapy being censored). In order to report outcomes on an ITT basis, survival outcomes were also assessed from time of treatment allocation for all patients considered eligible for tisagenlecleucel. Further, a more comprehensive event-free survival measure encompassing interval to molecular or frank relapse, further therapy, B cell recovery, death or treatment failure was analysed. Median follow up was calculated using a reverse Kaplan-Meier method.


Figure 1 demonstrates all patients: 66 patients were screened, 60 patients were deemed eligible for therapy (the ITT cohort), 57 patients were harvested and 49 infused. A total of 3 patients were not harvested and 2 not infused because of progressive disease (n=4) and 1 manufacturing failure. Patient and disease characteristics are summarised in Table 1. The cohort comprised patients with advanced ALL, having been treated with a median of 2.5 therapy lines not including HSCT (range 1-6), and with 47.5% of the cohort having had a prior HSCT. The median follow-up from infusion was 9.9 months and from treatment allocation for the ITT cohort was 11.9 months. The median lead time from allocation to infusion was 2 months.

The CR/CRi rate was 95% in the first 90 days, 78.9% were MRD-. On an ITT basis, CR/CRi rate was 84.8%. Median OS and EFS as defined in the ELIANA study were not reached. Overall survival at 6 and 12 months for infused patients was 97.6% and 86.1%, and for the ITT cohort was 90.4% and 78.3%. EFS for infused patients at 6 and 12 months were 74.8% and 68.2%, and for the ITT cohort were 78.5% and 60.9%. Of 49 patients infused, 14 (28.5%) received further therapy including 6 (8.2%) who received allogeneic SCT for relapse or B cell recovery. For patients relapsing following CR (n=10 infused) there were 4/10 CD19- relapses.

A composite EFS including molecular or frank relapse, further therapy, B cell recovery, death or treatment failure was analysed. Using this more stringent definition from infusion, the 6, 12 month EFS were 47.6%, and 33.6% and from treatment allocation for the ITT cohort were 63% and 34.3%

Toxicity outcomes are summarised in Table 2. Severe (grade ≥3) CRS, neurotoxicity, infection or cytopenia after day 30 post infusion occurred in 20.4%, 10.2% 27.1% and 54.2% respectively. 71.4% of the cohort developed hypogammaglobulinaemia, (Figure 3A). The 6 and 12 month probabilities of B cell depletion were 67.1% and 51.3% respectively.


Whilst registry data provide outcomes of large cohorts receiving Tisagenlecleucel, standardised data collection on complete populations are lacking. The framework of a national access scheme provides a unique opportunity to study outcomes on an ITT basis. The CR and MRD negative CR rates, as well as conventional EFS and OS and severe toxicities noted in our cohort compare favourably to published registry reports (Grupp et al., 2019). We found a greater proportion of CD19+ compared to CD19- relapses than noted in the ELIANA study. Consideration of OS and EFS on an ITT basis are informative for clinicians when screening patients for eligibility. If selected for presentation at ASH 2020, updated data will be presented

Disclosures: Ghorashian: Amgen: Honoraria; Novartis: Honoraria; UCLB: Patents & Royalties. O'Reilly: Gilead: Honoraria; Novartis: Honoraria, Other: Travel support. Roddie: Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria. Neill: Novartis: Other: Funded attendance at academic conferences; Celgene: Other: Funded attendance at academic conferences. Pagliuca: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Patel: Novartis: Honoraria, Other: travel support. Hough: Novartis: Other: Travel support.

*signifies non-member of ASH