Use of inotuzumab‐ozogamicin in a child with Down syndrome and refractory B‐cell precursor acute lymphoblastic leukemia

Murillo, Laura; Dapena, José Luís; Velasco, Pablo; Heredia, Cristina Díaz de

doi:10.1002/pbc.27562

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…Due to their poor outcomes with conventional intensive salvage therapy approaches, early use of CAR T-cell therapy as a curative strategy may be considered for this population (Table 2). The data available to date suggest that individuals with DS tolerate immunotherapies well with efficacy and toxic effects profiles similar to those without DS …”

Section: Treatment Of Relapsementioning

confidence: 99%

Management of Down Syndrome–Associated Leukemias

et al. 2023

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ImportanceDown syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared with children without DS.ObservationsA recent National Institutes of Health-sponsored conference, ImpacT21, reviewed research and clinical trials in children, adolescents, and young adults (AYAs) with DS-AL and are presented herein, including presentation and treatment, clinical trial design, and ethical considerations for this unique population. Between 10% to 30% of infants with DS are diagnosed with transient abnormal myelopoiesis (TAM), which spontaneously regresses. After a latency period of up to 4 years, 20% to 30% develop myeloid leukemia associated with DS (ML-DS). Recent studies have characterized somatic mutations associated with progression from TAM to ML-DS, but predicting which patients will progress to ML-DS remains elusive. Clinical trials for DS-AL have aimed to reduce treatment-related mortality (TRM) and improve survival. Children with ML-DS have better outcomes compared with non-DS AML, but outcomes remain dismal in relapse. In contrast, patients with DS-ALL have inferior outcomes compared with those without DS, due to both higher TRM and relapse. Management of relapsed leukemia poses unique challenges owing to disease biology and increased vulnerability to toxic effects. Late effects in survivors of DS-AL are an important area in need of further study because they may demonstrate unique patterns in the setting of chronic medical conditions associated with DS.Conclusions and RelevanceOptimal management of DS-AL requires specific molecular testing, meticulous supportive care, and tailored therapy to reduce TRM while optimizing survival. There is no standard approach to treatment of relapsed disease. Future work should include identification of biomarkers predictive of toxic effects; enhanced clinical and scientific collaborations; promotion of access to novel agents through innovative clinical trial design; and dedicated studies of late effects of treatment.

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Section: Treatment Of Relapsementioning

confidence: 99%

Management of Down Syndrome–Associated Leukemias

et al. 2023

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“…The most common toxicity was hematologic, and two deaths were reported, one due to toxic leukoencephalopathy and one due to SOS that occurred during HSCT [82]. InO has been used with success in patients with Down syndrome, but the data remain scarce [79,83,84].…”

Section: Special Pediatric Populationsmentioning

confidence: 99%

Immunotherapy in Pediatric B-Cell Acute Lymphoblastic Leukemia: Advances and Ongoing Challenges

et al. 2020

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Leukemia, most commonly B-cell acute lymphoblastic leukemia (B-ALL), accounts for about 30% of childhood cancer diagnoses. While there have been dramatic improvements in childhood ALL outcomes, certain subgroups-particularly those who relapse-fare poorly. In addition, cure is associated with significant short-and long-term side effects. Given these challenges, there is great interest in novel, targeted approaches to therapy. A number of new immunotherapeutic agents have proven to be efficacious in relapsed or refractory disease and are now being investigated in frontline treatment regimens. Blinatumomab (a bispecific T-cell engager that targets cluster of differentiation [CD]-19) and inotuzumab ozogamicin (a humanized antibody-drug conjugate to CD22) have shown the most promise. Chimeric antigen receptor T (CAR-T) cells, a form of adoptive immunotherapy, rely on the transfer of genetically modified effector T cells that have the potential to persist in vivo for years, providing ongoing long-term disease control. In this article, we discuss the clinical biology and treatment of B-ALL with an emphasis on the role of immunotherapy in overcoming the challenges of conventional cytotoxic therapy. As immunotherapy continues to move into the frontline of pediatric B-ALL therapy, we also discuss strategies to address unique side effects associated with these agents and efforts to overcome mechanisms of resistance to immunotherapy.

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“…After informed consent signed by legal guardian, all patients, classified either refractory in one patient or as early relapse in the remaining two patients, received blinatumomab as re-induction treatment with commercially available drug (two patients) or compassionate use after approval of Ethical Committee. Debulking therapy was administered including one course of inotuzumab in one patient 7 and four weekly doses of vincristine in the other two patients in order to reduce tumour burden. The dose of blinatumomab was administered All patients achieved morphological CR, and two out of three MRD negativity by flow cytometry, after subsequent courses.…”

mentioning

confidence: 99%