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Review
. 2022 Oct;22(10):718-725.
doi: 10.1016/j.clml.2022.07.010. Epub 2022 Jul 20.

SOHO State of the Art Updates and Next Questions | Novel Approaches to Pediatric T-cell ALL and T-Lymphoblastic Lymphoma

Ryan J Summers  1 , David T Teachey  2
Affiliations
Review

SOHO State of the Art Updates and Next Questions | Novel Approaches to Pediatric T-cell ALL and T-Lymphoblastic Lymphoma

Ryan J Summers et al. Clin Lymphoma Myeloma Leuk. 2022 Oct.

Abstract

While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LL) have improved significantly with contemporary therapy, outcomes for patients with relapsed or refractory (r/r) disease remain dismal. Improved risk stratification and the incorporation of novel therapeutics have the potential to improve outcomes further in T-ALL/T-LL by limiting relapse risk and improving salvage rates for those with r/r disease. In this review we will discuss the challenges and new opportunities for improved risk stratification in T-ALL and T-LL. We will further discuss the recent incorporation of the novel therapeutics nelarabine and bortezomib into front-line therapy for children with T-ALL and T-LL. Finally, we will address new classes of targeted small molecule inhibitors, immunotherapeutics, and chimeric antigen receptor T-cell therapies under investigation in r/r T-ALL and T-LL.

Keywords: Acute lymphoblastic leukemia; Chimeric antigen receptor T-cells; Immunotherapy; Proteasome inhibitors; Small molecule inhibitors.

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Conflict of interest statement

Declaration of Interest:

Summers RJ: none

Teachey DT: DTT has patents pending on CD38 CAR-T cells for hematologic malignancies and biomarkers for cytokine release syndrome. DTT receives research funding from BEAM Therapeutics and NeoImmune Tech. DTT serves on advisory boards for Sobi, Janssen, and BEAM Therapeutics.

Figures

Figure 1.
Figure 1.. T-ALL Biology.
T-ALL can be divided into groups based on genetic alterations that lead to dysregulation of potentially targetable functional pathways (outer ring) or based on increased expression of different transcription factors (inner ring). Percents are frequencies in the TARGET T-ALL cohort. High risk (<70% 5-year event-free survival), Intermediate risk (70–90%), Low risk (>90%) – rates are not adjusted for MRD. Adapted from Teachey and Pui, Lancet Oncology 2019.
Figure 2.
Figure 2.. T-LL patients had improved OS with bortezomib.
4-year OS for AALL1231 T-ALL (left panel) patients randomized to the bortezomib arm was 87.9%± 2.1% compared with 88.3%±2.1% without bortezomib (P=.469). 4-year OS for T-LL (right panel) was 89.5%±3.6% with bortezomib vs 78.3%±4.9% without bortezomib (P=.009). Adapted from Teachey et al. Journal of Clinical Oncology 2022.
Figure 3.
Figure 3.. Incorporation of novel therapeutics into therapy for relapsed/refractory T-ALL/T-LL.
Blue boxes represent potential opportunities to incorporate novel therapeutics into therapy for relapsed/refractory T-ALL/T-LL. Abbreviations: CAR-T – chimeric antigen receptor T-cell; HSCT – hematopoietic stem cell transplant
See this image and copyright information in PMC

References

    1. Teachey DT, O’Connor D: How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children. Blood 135:159–166, 2020 - PMC - PubMed
    1. Teachey DT, Pui C-H: Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. The Lancet Oncology 20:e142–e154, 2019 - PMC - PubMed
    1. Burkhardt B, Hermiston ML: Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. British Journal of Haematology 185:1158–1170, 2019 - PubMed
    1. Hayashi RJ, Winter SS, Dunsmore KP, et al.: Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children’s Oncology Group AALL0434. Journal of Clinical Oncology 38:3062–3070, 2020 - PMC - PubMed
    1. Vora A, Goulden N, Mitchell C, et al.: Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol 15:809–18, 2014 - PubMed

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