Phase 1 Dose Escalation Trial of Pegcrisantaspase in Combination with Venetoclax in Adults with Relapsed or Refractory Acute Myeloid Leukemia

Bollino, Dominique; Liu, Yuchen; Bah, Osman M.; Caprinolo, Katherine; Zarrabi, Jinoos; Philip, Sunita; Mostafa, Ezzat; Lapidus, Rena G.; Singh, Zeba N.; Kallen, Michael E.; Ning, Yi; Koka, Rima; Niyongere, Sandrine; Duong, Vu H.; Strovel, Erin T; Graveno, Molly; Emadi, Ashkan

doi:10.1182/blood-2022-159621

Cited by 2 publications

(3 citation statements)

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“…In this study, treatment was associated with remission rates of 19% with an anti-leukemic signal in IDH-mutated patients [41]. Several prospective trials and retrospective analyses have since examined venetoclax-based regimens in R/R disease (Table 1) [42‒55]. For example, a multicenter retrospective study examined HMA and venetoclax for patients who are refractory to HMA or relapsed after previous HMA exposure and showed CR/CRi in 43% with an OS of 74% at 6 months [42].…”

Section: Experimental Non-immunotherapeutic Approaches For R/r Amlmentioning

confidence: 99%

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Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024

Buchrits,

Wolach

2023

Acta Haematol

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Background: Relapsed or refractory (R/R) acute myeloid leukemia (AML) is a challenging, high-risk, clinical scenario with a dismal outcome. Recent insights on the genetic, epigenetic, and metabolic events that drive clonal progression and the advent of novel therapies resulted in the incorporation of several new targeted therapies, alone or in combination, in the R/R setting with the aim of improving response rates and survival. Herein we review current challenges and future opportunities with non-immunotherapeutic approaches to treat R/R AML. Summary: Inhibitors of FLT3 and IDH 1/2 are now FDA-approved for patients with R/R disease and corresponding mutations. These agents are also used in combination with intensive and low-intensity platforms in an attempt to improve response and survival. Several targeted agents are currently being tested alone or in combination in early-phase trials. These include drugs that target apoptotic pathways, drugs that interfere with key survival pathways of the R/R leukemic cell as well as therapies aimed towards the leukemia marrow microenvironment. Menin inhibitors are a promising class of active drugs in NPM1 and KMT2A-rearranged AML. Key-messages: Several new targeted therapies, immunologic and non-immunologic are being studied and are moving through pre-clinical and clinical pipelines. Significant remaining challenges include the development of synergistic combination therapies tailored to the specific biology and clinical context of the patient, and re-defining the role and timing of allogeneic transplantation in patients with R/R disease.

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Section: Experimental Non-immunotherapeutic Approaches For R/r Amlmentioning

confidence: 99%

“…This phase Ib clinical trial (NCT04666649) included 11 R/R patients. ORR was 64%, including 3 pts (27%) with CR/CRh/CRi, 2 of whom were previously exposed to venetoclax [46].…”

Section: Experimental Non-immunotherapeutic Approaches For R/r Amlmentioning

confidence: 99%

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024

Buchrits,

Wolach

2023

Acta Haematol

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“…Pegcrisantastase (PegC) is a long-acting crisantastase that exhibits strong anti-leukemia activity through complete consumption of glutamine. An open-label phase Ib clinical trial [ 14 ] evaluated the combination of VEN with PegC in R/R AML. The ORR was 64%, with no serious asparaginase-related AE of interest observed.…”

Section: Ven Combined With Antibodies or Targeted Drugs For R/r Amlmentioning

confidence: 99%

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting

Gong

Zhang

et al. 2023

Exp Hematol Oncol

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Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

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Phase 1 Dose Escalation Trial of Pegcrisantaspase in Combination with Venetoclax in Adults with Relapsed or Refractory Acute Myeloid Leukemia

Cited by 2 publications

References 0 publications

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting

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