Venetoclax and decitabine for relapsed paediatric myelodysplastic syndrome‐related acute myeloid leukaemia with complex aberrant karyotype after second stem cell transplantation

Raedler, Johannes; Heyde, Sita; Kolokythas, Marie; Eichinger, Anna; Binder, Vera; Schmid, Irene; Klein, Christoph; Feuchtinger, Tobias; Albert, Michael H.

doi:10.1111/bjh.16682

Cited by 6 publications

(5 citation statements)

References 13 publications

(22 reference statements)

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“…Venetoclax has already been described as effective in adults with RR ALL, especially T-cell ALL, with particular attention paid to ETP ALL [ 26 , 31 , 32 ]. More recently, it was shown to be beneficial and safe in the pediatric population for myelodysplastic syndrome and AML, and there are emerging but sparse data on its use in lymphoid malignancies in pediatrics [ 27 , 33 , 34 , 35 , 36 ]. Pullarkat et al, in a study that combined venetoclax, navitoclax, and low-dose chemotherapy for RR lymphoblastic leukemia/lymphoma, demonstrated favorable results in 12 pediatric patients with ALL, with a 75% response rate [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Gibson

Trabal

McCall

et al. 2021

Cancers

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Venetoclax is approved for adult patients with chronic lymphocytic leukemia and acute myeloid leukemia. Expanding its use to the pediatric population is currently under investigation, but more robust data are needed. We retrospectively analyzed the safety and efficacy of venetoclax in children/AYA with ALL/LBL. We identified 18 patients (T-cell ALL, n = 7; T-cell LBL, n = 6; B-cell ALL, n = 5) aged 6–22 years. No new venetoclax safety signals were identified; the most common toxicity was myelosuppression. No deaths occurred within 30 days from the start of the therapy. A mean of 2.6 (range 0–8) prior lines of therapy were given. The mean duration of venetoclax was 4.06 months (range 0.2–24.67 months). Complete remission was achieved in 11 (61%) patients. Of the eight patients who remain alive, four are continuing on venetoclax combination therapy, and four proceeded to hematopoietic stem cell transplantation. Three patients who initially achieved CR, later relapsed, and are deceased. Nine patients are deceased, and one patient was lost to follow-up. Overall survival is 9.14 months (range 1.1–33.1), and progression-free survival is 7.34 months (range 0.2–33.1). This is the largest cohort of pediatric/AYA patients who received venetoclax for ALL/LBL. Our data support the consideration of venetoclax-based regimens in pediatric patients with R/R ALL/LBL and its investigation as upfront therapy for T-cell ALL/LBL.

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Section: Discussionmentioning

confidence: 99%

Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Gibson

Trabal

McCall

et al. 2021

Cancers

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“…Although we did not perform a second cytogenetic analysis at relapse, it is possible that AML cells had acquired a complex karyotype, as described in refractory disease ( 21 ). Given worsening toxicity from chemotherapy courses, we chose to try a combination of venetoclax and azacitidine, based on adult experience and small pediatric case series ( 22 – 24 ). There is little data on experience with venetoclax for myeloid malignancies in children.…”

Section: Discussionmentioning

confidence: 99%

Case report: Venetoclax therapy in a boy with acute myeloid leukemia in Shwachman Diamond syndrome

et al. 2023

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Shwachman-Diamond syndrome (SDS) is a rare bone marrow failure syndrome characterized by exocrine pancreatic insufficiency, bone abnormalities, progressive cytopenia, and predispositions to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). AML, in these patients, is associated with a poor prognosis and with an increased risk of organ toxicity and infectious complications from chemotherapy and hematopoietic stem cell transplantation (HSCT), thus leading to high rates of treatment-related morbidity and mortality. The BCL-2 inhibitor venetoclax has revolutionized the treatment of AML in elderly adults, especially for treatment-naive elderly patients who are ineligible for intensive chemotherapy. There is limited evidence on the use of venetoclax in pediatric patients with SDS-related MDS or AML. Here, we report a case of a 14-year-old boy with SDS with AML arising from MDS. The patient was treated with two cycles of conventional chemotherapy with fludarabine and cytarabine with an initial good response but immediate relapse and substantial toxicity. Treatment with venetoclax and azacitidine was started, with a substantial reduction of leukemic burden (good response on peripheral leukemic infiltration and partial response in the bone marrow after one course). However, it was followed by multiple infectious complications and worsening of the general condition not allowing treatment to be continued, and the patient eventually died from multiorgan failure. With the limitations of observation of a single patient, our experience suggests that venetoclax/azacitidine combination therapy may represent a therapeutic possibility for patients with SDS and AML, even though it may be associated with significant toxicity.

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“…In paediatrics, the tested applications are much fewer but new and exciting results were recently presented establishing venetoclax as an active agent in relapsed or refractory leukaemias, and strongly supporting clinical attempts or trials of BH3 mimetics in other diseases and clinical scenarios in childhood cancers [ 2 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. The importance of the paediatric-relevant experience in AML/MDS, which are main areas of development in adults, is linked to its relatively low prevalence and differences from older patients in terms of genetic features and heterogeneity of myeloid neoplasia in children, resulting in difficulties in extrapolating data on BH3 mimetics from adults.…”

Section: Introductionmentioning

confidence: 94%

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey

et al. 2023

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Venetoclax, the best established BH3 mimetic, is a practice-changing proapoptotic drug to treat blood cancers in adults. In paediatrics, the data are less but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the interventions could be potentially molecularly guided as vulnerabilities to BH3 mimetics were reported. Currently, venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated thus far with venetoclax in Poland. We set out to gather this data to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data of November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with haematologic complete remission (CR), was reported in five patients out of ten, whereas five patients did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe that BH3 mimetics have clinical activity in children and should be available to paediatric haemato-oncology practitioners in well-selected applications.

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Venetoclax and decitabine for relapsed paediatric myelodysplastic syndrome‐related acute myeloid leukaemia with complex aberrant karyotype after second stem cell transplantation

Cited by 6 publications

References 13 publications

Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Venetoclax for Children and Adolescents with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Case report: Venetoclax therapy in a boy with acute myeloid leukemia in Shwachman Diamond syndrome

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey

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