Sequential Therapy of Inotuzumab Ozogamicin and Blinatumomab as a Bridge-to Hematopoietic Stem Cell Transplantation in a Pediatric Patient With Primary Refractory Acute Lymphoblastic Leukemia: A Case Report

Uchida, Eriko; Kurata, Tadao; Komori, Kazutoshi; Kobayashi, Jun; Kubota, Noriko; Sakashita, Kazuo

doi:10.1097/mph.0000000000002205

Cited by 3 publications

(3 citation statements)

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“…After receiving blinatumomab treatment for 4 weeks, lineage transformation occurred, and the infant eventually died of the primary disease. Recently, some scholars ( 22 , 23 ) explored blinatumomab combined with other antibodies to achieve complete molecular remission in relapsed/refractory ALL or MPAL. Dual-targeted antibody therapy may be an option for some patients with refractory and relapsed ALL or MPAL; however, many prospective studies still need to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study

et al. 2023

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BackgroundThe 5-year event-free survival rate for childhood acute lymphoblastic leukemia (ALL) has increased to more than 85%. However, the 5-year overall survival rate in children with relapsed/refractory ALL did not exceed 50%. In the past decade, immunotherapies (such as blinatumomab and chimeric antigen receptor T-cell therapy) were approved for relapsed/refractory B-ALL, transforming the treatment environment for children with relapsed/refractory ALL.ObjectiveThis study aimed to explore how immunotherapy can be incorporated into salvage regimens for pediatric patients with relapsed/refractory ALL by retrospectively analyzing the diagnosis and treatment process of seven children with relapsed/refractory leukemia and observing the side effects of the two strategies and long-term survival.MethodsThe clinical features and treatment responses of patients aged <14 years with relapsed/refractory leukemia who received immunotherapy (including Chimeric Antigen Receptor T cell treatment and blinatumomab) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between February 2014 and April 2022 were retrospectively analyzed.ResultsSeven children underwent immunotherapy. Five patients received immunotherapy and sequential allogeneic hematopoietic stem cell transplantation (HSCT), whereas the other two received only immunotherapy. Five patients achieved complete remission (71.4%). None of the patients had severe cytokine release syndrome. However, one developed grade 3 immune effector cell-associated neurotoxicity syndrome with prior leukoencephalopathy. The median follow-up period was 541 days (range, 186–3,180 days). No deaths were related to treatment. Three patients relapsed, two had CD19-negative recurrences, and the third showed CD19 antigen reduction. One patient died after disease progression, whereas the other died of HSCT-related complications. One patient abandoned the treatment after relapse and was lost to follow-up.ConclusionBlinatumomab and CAR T-cell therapy showed excellent remission rates and manageable toxicity in pediatric patients with relapsed/refractory leukemia. However, the duration of the remission was limited. Therefore, further prospective randomized clinical studies should be conducted to improve the long-term efficacy of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study

et al. 2023

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“…Blinatumomab-bridging HSCT should be initiated promptly to improve patient outcomes after a short course of blinatumomabinduced remission. Uchida et al reported a case in which molecular CR was achieved with localized chronic graft-vs.-host disease in a patient who underwent HSCT on the 22nd day after CR in the bone marrow (42). In another study, Chen et al reported the outcomes of two children who underwent allogeneic HSCT within one month of blinatumomab treatment with no implant failure.…”

Section: Discussionmentioning

confidence: 99%

Short-course blinatumomab for refractory/relapse precursor B acute lymphoblastic leukemia in children

et al. 2023

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ObjectiveTo evaluate the clinical efficacy and safety of a short course of blinatumomab in children with refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R-BCP-ALL).MethodsThe clinical data of 33 R/R BCP-ALL children aged 0–18 years who underwent a short course of blinatumomab (14 days) between August 2021 and November 2022 were retrospectively collected and analyzed.ResultsAmong 33 patients with BCP-ALL, 26 achieved complete remission (CR), with a total remission rate of 78.8% (26/33). The duration of remission was approximately 14 days. Of the 7 children without CR, 5 were still in remission at 28 days. In 11 patients with refractory disease and 22 with recurrence, the remission rates were 90.9% (10/11) and 72.7% (16/22), respectively. The overall survival (OS) rates of the 26 patients with CR and seven patients without CR were 96.1% and 57.1% (p = 0.002), respectively, and the disease-free survival (DFS) rates were 96.1% and 42.9% (p < 0.001), respectively. Among the 26 patients with CR, 15 underwent bridging hematopoietic stem cell transplantation (HSCT) and 11 did not receive HSCT; with OS rates of 93.3% and 100% (p = 0.40) and DFS rates of 93.3% and 100% (p = 0.400), respectively. The OS for all patients was 87.9% (29/33) and the DFS was 84.8% (28/33). There were 18 cases (54.5%) of cytokine release syndrome (CRS), 2 cases (6.1%) of severe CRS (all grade 3), 1 case (3.0%) of immune effector cell-associated neurotoxicity syndrome (ICANS), 0 cases (0%) of ICANS ≥ grade 3, and no deaths caused by treatment.ConclusionsShort-term follow-up revealed a high R/R BCP-ALL remission rate in children treated with a short course of blinatumomab. The toxicity was low and controllable. No significant short-term survival benefits were observed after bridging HSCT with blinatumomab. In developing countries, a short course of blinatumomab can achieve satisfactory outcomes, while reducing household costs and saving medical resources.

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“…A recent case report describes an 11-year-old child with primary refractory ALL in whom repeated cycles of blinatumomab and InO allowed achievement of molecular remission, serving as bridging therapy to a successful HSCT ( 12 ).…”

Section: Strategies Prior To Hsctmentioning

confidence: 99%

Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL?

Kállay¹,

Algeri

Buechner

et al. 2022

Front. Pediatr.

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This review will address the place of innovative, non-chemotherapy, non-CAR-T targeted therapies in the treatment of Acute Lymphoblastic Leukaemia (ALL), focusing on their use in the hematopoietic stem cell transplant (HSCT) context. The focus will be on the agent with the most experience to date, namely the bispecific T-cell engater (BiTE) blinatumomab, but references to antibody-drug conjugates (ADCs) such as inotuzumab ozogamicin and monoclonal antibodies such as daratumamab will be made as well. Specific issues to be addressed include: (1) The use of these agents to reduce measurable residual disease (MRD) prior to HSCT and their potential for improved transplant outcomes due to reduced toxicity compared to traditional chemotherapy salvage, as well as potentially increased toxicity with HSCT with particular agents; (2) the appropriate sequencing of innovative therapies, i.e., when to use BiTEs or antibodies versus CARs pre- and/or post-HSCT; this will include also the potential for impact on response of one group of agents on response to the other; (3) the role of these agents particularly in the post-HSCT relapse setting, or as maintenance to prevent relapse in this setting; (4) special populations in which these agents may substitute for traditional chemotherapy during induction or consolidation in patients with predisposing factors for toxicity with traditional therapy (e.g., Trisomy 21, infants), or those who develop infectious complications precluding delivery of full standard-of-care (SOC) chemotherapy during induction/consolidation (e.g., fungal infections); (5) the evidence we have to date regarding the potential for substitution of blinatumomab for some of the standard chemotherapy agents used pre-HSCT in patients without the above risk factors for toxicity, but with high risk disease going into transplant, in an attempt to decrease current rates of transplant-related mortality as well as morbidity; (6) the unique toxicity profile of these agents and concerns regarding particular side effects in the HSCT context. The manuscript will include both the data we have to date regarding the above issues, ongoing studies that are trying to explore them, and suggestions for future studies to further refine our knowledge base.

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Sequential Therapy of Inotuzumab Ozogamicin and Blinatumomab as a Bridge-to Hematopoietic Stem Cell Transplantation in a Pediatric Patient With Primary Refractory Acute Lymphoblastic Leukemia: A Case Report

Cited by 3 publications

References 11 publications

Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study

Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study

Short-course blinatumomab for refractory/relapse precursor B acute lymphoblastic leukemia in children

Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL?

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