Lymphoma in Pediatrics 23rd Nov 2018 Prof. Mohammad Faranoush

Rituximab in childhood Non-Hodgkins lymphoma IR.MABSC.EDU.5.11.18

Back ground Since the late 1960s, treatment outcomes for pediatric patients with non-Hodgkin lymphoma have steadily improved. Even for patients with advanced disease, event-free survival rates are now 65-90%. IR.MABSC.EDU.5.11.18

Back ground The mainstay of conventional therapy is multiagent chemotherapy tailored to the histologic subtype and the clinical stage of disease. In certain individuals with non-Hodgkin lymphoma, surgical resection and radiation therapy are also key components of definitive treatment. Newer therapies that target immunologic and biologic aspects of the lymphoma are still under development but beginning to appear in the clinical arena. IR.MABSC.EDU.5.11.18

Classification According to the National Cancer Institute (NCI) formulation, most childhood non-Hodgkin lymphomas can be classified as one of the following types: Lymphoblastic lymphomas Small noncleaved cell lymphomas (SNCCLs) - Burkitt lymphomas and non-Burkitt lymphomas (Burkittlike lymphomas) Large cell lymphomas (LCLs) IR.MABSC.EDU.5.11.18 IR.MABSC.EDU.5.11.18

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Disease progression Most malignancies arise as disease localized in the organ or tissue of origin. They may then secondarily spread by means of local extension or distant metastases. In contrast, non-Hodgkin lymphoma is best regarded as a systemic disease, because of the unique anatomy of the lymphoid system and because of the physiology of lymphoid cells, which tend to migrate whether they are normal or malignant. The role of lymphoma stem cells in the genesis and maintenance of B-cell lymphomas remains speculative IR.MABSC.EDU.5.11.18

Table 3. Demographic characteristics of patients in PHIS-assembled cohort compared to the National Cancer Institute’s SEER program. Citrin R, Horowitz JP, Reilly AF, Li Y, Huang YS, et al. (2017) Creation of a pediatric mature B-cell non-Hodgkin lymphoma cohort within the Pediatric Health Information System Database. PLOS ONE 12(10): e0186960. https://doi.org/10.1371/journal.pone.0186960 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186960 IR.MABSC.EDU.5.11.18

Prognosis The overall prognosis for children with non-Hodgkin lymphoma has steadily improved. Period analysis of SEER data for children under 15 years showed that 5- and 10-year survival increased, respectively, from 76.6% and 73.0% in 1990-1994 to 87.7% and 86.9% in 2000-2004. The projected 10-year survival rate for children diagnosed in 2005-2009 was 90.6% IR.MABSC.EDU.5.11.18

prognosis Among patients with non-Hodgkin lymphoma, the major determinants of prognosis are histology and disease stage. The presence or absence of particular molecular markers (eg, anaplastic lymphoma kinase (ALK) and/or CD56 in anaplastic large cell lymphoma [LCL]) has additional prognostic significance IR.MABSC.EDU.5.11.18

Approach Considerations Progress in the treatment of children and adolescents with NHL parallels that of childhood acute lymphoblastic leukemia. IR.MABSC.EDU.5.11.18

Treatment Surgery Chemotherapy Radotherapy SCT Relapsed disease IR.MABSC.EDU.5.11.18

Monoclonal Ab Rituximab (anti-CD20 antibody) Pembrolizumab (monoclonal antibody that binds the programmed cell death-1 protein (PD-1) ligands PD-L1 and PL2) Obinutuzumab (GA101) Veltuzumab (IMMU-106) Blinatumomab (AMG103) bi-specific CD19/CD3T-cell engager Ibrutinib IR.MABSC.EDU.5.11.18

Indication IR.MABSC.EDU.5.11.18

Rituximab therapy in newly diagnosed pediatric NHL DLBCL and BL is the expression of the protein CD20. CD20 is an ideal target for antibody therapy Some study in pediatric patients with CD20– positive NHL hasnot yet to demonstrate an improvement in EFS or OS with the addition of frontline rituximab therapy IR.MABSC.EDU.5.11.18

Rituximab The intergroup Phase III trial, ANHL1131 (NCT01595048), which was designed to test the efficacy of frontline rituximab therapy in pediatric patients with B-cell NHL opened in 2010 Some improvement in OS up to 20% of patients who receive rituximab therapy will have prolonged hypogammaglobulinemia and impaired immune function IR.MABSC.EDU.5.11.18

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Summary Treatments for NHL may start to mimic those for pediatric acute leukemias, where minimal residual disease monitoring enables the identification of those patients who will require either escalation or subtraction of therapy. Novel frontline trials in pediatric patients with NHL using the several potentially useful agents may provide improvement of EFS while diminishing toxicity from standard chemotherapy. IR.MABSC.EDU.5.11.18

Doing now what patients need next