Efficacy of Non-Intensive Therapies Approved for Relapsed/Refractory Acute Myeloid Leukemia: A Systematic Literature Review

Russell-Smith, T. Alexander; Gurskyte, Laura; Muresan, Bogdan; Mamolo, Carla; Gezin, A.; Cappelleri, Joseph C.; Heeg, Bart

doi:10.2217/fon-2021-1355

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…RR-AML is attributed to genetic mutations in leukemia cells, the existence of leukemia stem cells, and resistance to treatment medications. These factors make patients refractory to traditional chemotherapy and radiotherapy, and it is difficult to completely cure [19]. Venclexta (Venclyxto) is an oral drug that inhibits the survival of leukemia cells by targeting the BCL-2 protein, thereby promoting the apoptosis of leukemia cells.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax in combination with azacitidine or decitabine in relapsed/refractory acute myeloid leukemia

Che,

Tan,

Liu

et al. 2024

Trop. J. Pharm Res

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Purpose: To investigate the clinical effects of venetoclax combined with azacitidine or decitabine in relapsed/refractory acute myeloid leukemia. Methods: 208 eligible first-line participants, who were diagnosed and treated for relapsed/refractory acute myeloid leukemia between January 2022 and December 2022, were recruited from the Department of Hematology of Loudi Central Hospital, China. The patients were randomly divided into study and control groups at the point of recruitment. Patients in the control group received venetoclax combined with decitabine, while those in the study group received venetoclax in combination with azacitidine. Clinical data for the two groups were recorded. The primary endpoints of this study included efficacy, routine blood indices, and adverse reactions. Results: There was no statistically significant difference in baseline characteristics between the two groups (p > 0.05), indicating comparability. The total effectiveness of the treatment (i.e., efficacy) in the study group was higher than in the control group (p < 0.05), while the control group had a higher risk of platelet, red blood cell, and neutrophil absolute count reduction than the study group (p < 0.05). The platelet count and hemoglobin level were lower in the control group after treatment compared to the study group (p < 0.05). Conclusion: The combination of venetoclax with azacitidine improves the efficacy and blood routine indices of patients with relapsed/ refractory acute myeloid leukemia, while reducing adverse reactions.

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Section: Discussionmentioning

confidence: 99%

Venetoclax in combination with azacitidine or decitabine in relapsed/refractory acute myeloid leukemia

Che,

Tan,

Liu

et al. 2024

Trop. J. Pharm Res

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“…While 40%–50% of patients with higher risk MDS respond to hypomethylating agents (HMAs), 6 , 7 responses are generally transient (<2 years), and prognoses post‐HMA failure are grim. 6 , 8 , 9 Despite new therapeutic strategies, r/rAML and r/rMDS represent high unmet medical needs; 10 , 11 no single standard‐of‐care approach exists.…”

Section: Introductionmentioning

confidence: 99%

First‐in‐human study of JNJ‐67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome

Narayan,

Piérola,

Donnellan

et al. 2024

Clinical Translational Sci

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Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ‐67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first‐in‐human, open‐label, phase I, dose‐escalation/dose‐expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ‐67571244 was administered intravenously or subcutaneously using step‐up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose‐escalation cohorts (n = 68) and before starting dose‐expansion. Overall, 11 (16.2%) patients experienced ≥1 dose‐limiting toxicity; all experienced ≥1 treatment‐emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ‐67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion‐related reactions, and elevated liver function tests. A prolonged step‐up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T‐cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ‐67571244 efficacy was not achieved, thus MTD and RP2D were not determined.

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“…Hematologic neoplasms comprise a heterogeneous group of diseases that interfere with the normal production of blood cells, among which, acute leukemias stand out for their high mortality and recurrence rates [ 1 ]. Despite the great advances in understanding the biology of these diseases which has resulted in the approval of new drugs, the therapeutic options are still scarce for the relapsed/refractory patients [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular and Molecular Effects of Eribulin in Preclinical Models of Hematologic Neoplasms

Vicari

Lima

Costa-Lotufo

et al. 2022

Cancers

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Despite the advances in understanding the biology of hematologic neoplasms which has resulted in the approval of new drugs, the therapeutic options are still scarce for relapsed/refractory patients. Eribulin is a unique microtubule inhibitor that is currently being used in the therapy for metastatic breast cancer and soft tissue tumors. Here, we uncover eribulin’s cellular and molecular effects in a molecularly heterogeneous panel of hematologic neoplasms. Eribulin reduced cell viability and clonogenicity and promoted apoptosis and cell cycle arrest. The minimal effects of eribulin observed in the normal leukocytes suggested selectivity for malignant blood cells. In the molecular scenario, eribulin induces DNA damage and apoptosis markers. The ABCB1, ABCC1, p-AKT, p-NFκB, and NFκB levels were associated with responsiveness to eribulin in blood cancer cells, and a resistance eribulin-related target score was constructed. Combining eribulin with elacridar (a P-glycoprotein inhibitor), but not with PDTC (an NFkB inhibitor), increases eribulin-induced apoptosis in leukemia cells. In conclusion, our data indicate that eribulin leads to mitotic catastrophe and cell death in blood cancer cells. The expression and activation of MDR1, PI3K/AKT, and the NFκB-related targets may be biomarkers of the eribulin response, and the combined treatment of eribulin and elacridar may overcome drug resistance in these diseases.

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Efficacy of Non-Intensive Therapies Approved for Relapsed/Refractory Acute Myeloid Leukemia: A Systematic Literature Review

Cited by 4 publications

References 37 publications

Venetoclax in combination with azacitidine or decitabine in relapsed/refractory acute myeloid leukemia

Venetoclax in combination with azacitidine or decitabine in relapsed/refractory acute myeloid leukemia

First‐in‐human study of JNJ‐67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome

Cellular and Molecular Effects of Eribulin in Preclinical Models of Hematologic Neoplasms

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