Induction Chemoimmunotherapy and Consolidation With Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplant in Advanced Stage Mature T/Nk-Cell Lymphoma/Leukemia in Children, Adolescent, and Young Adults

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2022

DOI

10.1002/pbc.299522

Journal Title

Pediatric Blood and Cancer

Department

Pediatrics

Abstract

Background and Aims: Mature T/NK-cell lymphomas (MTCL) are rare among children, adolescent, and young adult (CAYA) and associated with dismal outcomes. For instance, we reported US outcomes of pediatric MTCL and found that patients with peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma (ENKL), or hepatosplenic Tcell lymphoma (HTCL) have very guarded prognosis (5-year OS 59%, 47%, and 9.6%, respectively), highlighting the urgent need for new therapies (Sorge, Cairo, Xavier. BJH 2019). Despite significant progress in the understanding of lymphoma cell biology, its microenvironment and the development of novel therapies targeting T/NK lymphomas, no standard of care treatment has been established for MTCL in CAYA patients. Methods: Multicenter pilot study for patients with de novo stage III/IV ENKL/aggressive NK-cell leukemia (cohort 1) or other mature TCL (cohort 2). Cohort 1 receive a combination of daratumumab, dexamethasone, methotrexate, ifosfamide, calaspargase, and etoposide (D-SMILE). If CR after 2 induction cycles patients undergo consolidation with reduced toxicity conditioning (RTC) and allogeneic stem cell transplant (alloSCT). Patients not in CR after induction can receive pembrolizumab with the goal of achieving an optimal disease status before alloSCT. Cohort 2 patients receive brentuximab vedotin, cyclophosphamide, doxorubicin (Bv-CHP). Cohort 2 in CR after 2 induction cycles undergo consolidation with RTC and alloSCT. Patients not in CR after induction can receive pralatrexate with the goal of achieving an optimal disease status before alloSCT. Forty patients age ≥ 12 months and < 31 years will be enrolled with a primary objective to assess safety and ORR by central imaging review of the 2 induction regimens and safety and feasibility of consolidation with RTC and alloSCT. Secondary endpoints include EFS, OS, and probability of nonengraftment, donor chimerism, acute and chronic GVHD, hematopoietic and immune reconstitution post RTC and alloSCT. NCT03719105. Clinical trial supported by Pediatric Cancer Research Foundation and Servier Pharmaceutics. Results: In progress. Conclusions: In progress.

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