Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review

Int J Mol Sci. 2023 Sep 30;24(19):14780. doi: 10.3390/ijms241914780.

Abstract

The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin's lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy.

Keywords: checkpoint inhibitors; chimeric antigen receptor-T; combined therapy; haematologic tumour; systematic review.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Hematologic Neoplasms* / therapy
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy, Adoptive / methods
  • Neoplasm Recurrence, Local
  • Programmed Cell Death 1 Receptor
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes

Substances

  • Immune Checkpoint Inhibitors
  • Receptors, Chimeric Antigen
  • Programmed Cell Death 1 Receptor

Grants and funding

This research received no external funding.