CAR-based Cellular Therapy: clinical ePoster

A108 - CYTOPENIAS AFTER TISAGENLECLEUCEL IN PAEDIATRIC/YOUNG ADULT PATIENTS WITH REFRACTORY/RELAPSE B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA (R/R B-ALL): A REAL-LIFE SINGLE-CENTRE EXPERIENCE (ID 644)

Authors
  • I. Gómez-Centurión
  • S. Burridge
  • J. Silva
  • A. Lazareva
  • M. Gabelli
  • O. Mirci-Danicar
  • G. Lucchini
  • R. Chiesa
  • K. Rao
  • S. Samarasinghe
  • P. Veys
  • A. Vora
  • P. Amrolia
  • S. Ghorashian

Abstract

Background:
Tisagenlecleucel (KymriahTM) is a CD19-targeted CAR-T cell therapy approved for r/r B-ALL in paediatric/young-adult patients. Cytopenias following CAR-T cells are relatively common across multiple studies1 including those targeting CD19 and CD22 and are therefore not antigen-specific. The incidence and clinical impact of persistent or recurrent cytopenias has been under-recognized in clinical studies to date and the aetiology is as yet unclear. The objective of this study is to describe cytopenias and related complications in paediatric/young-adult patients with r/r B-ALL treated with Tisagenlecleucel.
[1]Jacoby et al. https://doi.org/10.1038/s41409-019-0487-3

Methods:
We retrospectively analyzed 12 consecutive patients with r/r B-ALL treated with Tisagenlecleucel between January 2019 and November 2019 in a single centre. Patients received lymphodepletion with fludarabine (120 mg/m2) and cyclophosphamide (1000 mg/m2). Cytopenias were graded according to CTCAE V-5.0. Persistent cytopenias were defined as grade 2-4 cytopenias after day-28. Recurrent cytopenias were defined as new-onset grade 3-4 cytopenias after day-28 when and after achieving normal counts on day-28. Cytopenias were considered resolved when grade 1 or normal counts were achieved.

Results:
Patient characteristics are summarised in Table 1. Nine patients were diagnosed with relapsed B-ALL after HSCT, 2 had relapsed B-ALL with a contraindication for HSCT and 1 had primary refractory disease. With a median follow-up of 4 months (range 1-10) after CAR-T cell infusion, MRD was negative in 11 patients (92%), B cell aplasia was persistent in 10 (83%) and 1 (8%) had a relapse and died.
Eight patients (67%) presented with grade 2-4 cytopenias before lymphodepletion (Figure 1).
Before day-28, all patients developed grade 2-4 anaemia (9=75% grade 3-4), 8 patients (67%) developed grade 2-4 thrombocytopenia (6=50% grade 3-4), and all patients developed grade 3-4 neutropenia.
Four patients (33%) had persistent grade 2-4 anaemia, 2 (17%) grade 3-4. Five (42%) had persistent thrombocytopenia, all grade 3-4. Seven (58%) had persistent neutropenia, all grade 3-4. Two patients (17%) with normal counts on day-28, developed recurrent grade 3-4 neutropenia after day-28.
Secondary causes of cytopenias were excluded. Among patients with persistent cytopenias, 4 (50%) had a hypocellular marrow on histology of the BM trephine.
Eight patients (67%) received at least one RBC transfusion before day-28, and 2 (17%) after day-28. Three patients (25%) received at least one platelet transfusion before day-28, and 4 (33%) after day-28. Seven patients (58%) received at least one Filgrastim dose after day-28. Eight documented infections were diagnosed, 3 of them after day-28, with 0% of infection-related mortality.
At last follow-up, anaemia was resolved in all patients, 2 (17%) had ongoing thrombocytopenia, (1 with platelet transfusion dependence), and 3 (25%) ongoing neutropenia (1 with Filgrastim dependence).

Conclusions:
Cytopenias were frequent in patients treated with Tisagenlecleucel. Whilst early cytopenias are expected due to lymphodepletion, mechanisms of persistent and recurrent cytopenias are unclear and might be related to CAR-T cells persistence. More studies are needed to determine etiology and risk factors for persistent cytopenias. Cytopenias are of relevance in terms of increased requirement for supportive care, however, in our cohort, were not associated with significant or persisting complications.


[Cytopenias following Tisagenlecleucel]

 

Disclosure:
Nothing to declare

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