Safety and Efficacy of Cusatuzumab in Combination with Venetoclax and Azacitidine (CVA) in Patients with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Eligible for Intensive Chemotherapy; An Open-Label, Multicenter, Phase 1b Study

Roboz, Gail J.; Pabst, Thomas; Aribi, Ahmed; Brandwein, Joseph; Döhner, Hartmut; Fiedler, Walter; Gandini, Domenica; Geddes, Michelle; Hou, Jing-Zhou; Howes, Angela; Hultberg, Anna; Huselton, Eric; Jacobs, Julie; Kane, Colleen; Lech‐Marańda, Ewa; Louwers, Marieke; Nottage, Kerri; Platzbecker, Uwe; Rampal, Raajit K.; Salman, Mariya; Shah, Parth; Stevens, Don A.; Stuart, Monic J.; Subklewe, Marion; Sumbul, Anne; Wang, Eunice S.; Wierzbowska, Agnieszka; Yao, Bin; Yee, Karen; Kantarjian, Hagop; Borthakur, Gautam

doi:10.1182/blood-2021-150371

Cited by 9 publications

(4 citation statements)

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“…In 2021, the preliminary results of the therapy combination Cusatuzumab plus AZA/VEN in ND AML patients ineligible for chemotherapy were presented: among the evaluable 42 patients, the ORR was 92.9% (CR 47.6%, CRi 57.1%, MLFS 11.9%). Apart from the IrAE (11.4% of patients with 2.3% at grade ≥ 3), the safety profile was consistent with that previously reported for the AZA/VEN regimen [140].…”

Section: Cd27/cd70 Pathwaysupporting

confidence: 88%

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

Guarnera,

Bravo-Perez,

Visconte

2023

Bioengineering

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In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies, such as antibody-based therapy, checkpoint inhibitors, and chimeric antigen receptor strategies, successfully tested in other hematologic malignancies, were very high. The inherent characteristics of AML blasts hampered the development of these treatments, and the path of immunotherapy in AML has been bumpy. Herein, we provide a detailed review of potential antigenic targets, available data from pre-clinical and clinical trials, and future directions of immunotherapies in AML.

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Section: Cd27/cd70 Pathwaysupporting

confidence: 88%

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

Guarnera,

Bravo-Perez,

Visconte

2023

Bioengineering

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“…Another promising regimen that recently entered the clinic is a combination of cusatuzumab and venetoclax (+/− azacitidine) (NCT04150887) [141]. BCL-2 plays an important role in the survival and persistence of AML blasts by sequestering pro-apoptotic BAX.…”

Section: Combination Regimens Evaluated In Clinical Settingmentioning

confidence: 99%

The CD70-CD27 axis in oncology: the new kids on the block

Flieswasser

Eynde

Audenaerde³

et al. 2022

J Exp Clin Cancer Res

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The immune checkpoint molecule CD70 and its receptor CD27 are aberrantly expressed in many hematological and solid malignancies. Dysregulation of the CD70-CD27 axis within the tumor and its microenvironment is associated with tumor progression and immunosuppression. This is in contrast to physiological conditions, where tightly controlled expression of CD70 and CD27 plays a role in co-stimulation in immune responses. In hematological malignancies, cancer cells co-express CD70 and CD27 promoting stemness, proliferation and survival of malignancy. In solid tumors, only expression of CD70 is present on the tumor cells which can facilitate immune evasion through CD27 expression in the tumor microenvironment. The discovery of these tumor promoting and immunosuppressive effects of the CD70-CD27 axis has unfolded a novel target in the field of oncology, CD70.In this review, we thoroughly discuss current insights into expression patterns and the role of the CD70-CD27 axis in hematological and solid malignancies, its effect on the tumor microenvironment and (pre)clinical therapeutic strategies.

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“…Similarly, the open-label, multicenter, phase Ib ELEVATE study aimed to test cusatuzumab combined with venetoclax and azacitidine in patients with previously untreated AML who are not eligible for intensive chemotherapy. 75 After a median follow-up of 40 weeks, 77% of patients achieved CR+CRi, with an MRD negativity rate of 50%.…”

Section: Combinations With Bcl-2 Inhibitionmentioning

confidence: 94%

The Evolving Treatment Landscape of AML

2022

healthbook TIMES Onco Hema

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For decades, intensive induction therapy consisting of a 7-day continuous infusion of cytarabine and a 3-day course of daunorubicin or idarubicin ("7+3") has been the backbone of acute myeloid leukemia (AML) treatment. 1,2 This regimen achieves durable response mainly in young and fit patients with favorable-risk AML. However, most patients with AML are older than 65 years with multiple comorbidities and the clinical outcomes in this population are poor, mostly due to unfavorable-risk genetics and low tolerance to intensive chemotherapy. 3,4 Recently, CPX-351, a liposomal formulation with a fixed combination of cytarabine and daunorubicin, has been approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of newly diagnosed AML patients with a poor prognosis. 5,6 In the randomized, phase III CLTR0310-301 trial, the liposomeencapsulated combination versus the standard combination of cytarabine and daunorubicin ("7+3" regimen) was associated with significantly prolonged median overall survival (OS) (9.6 months vs 5.9 months; HR: 0.69 [95% CI: 0.52−0.90]; p=0.005) in patients aged 60-75 years with newly diagnosed high-risk or secondary AML. 7 The improved OS with CPX-351 versus "7+3" was maintained after a follow-up of 5 years in this patient population. 8 The antitumor activity of this therapy was also demonstrated in a real-world analysis of highrisk AML patients treated with frontline CPX-351, with a median OS of 21 months and a 1-year OS rate of 64% after a median follow-up of 9.3 months. 9 A very recent retrospective comparative analysis further demonstrated that CPX-351 versus hypomethylating agent (HMA) plus venetoclax, a B-cell lymphoma-2 (BCL-2) protein inhibitor, was associated with prolonged OS in the overall population (range, 34−93 years). 10 However, there was no difference in clinical outcomes between the two treatment regimens in the group of patients aged 60−75 years, despite a more than the doubled rate of transplant in the CPX-351 arm.Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with poor long-term survival and a high relapse rate, mainly due to relapse and resistance to available therapies. The recent advancements in the technologies for genomic profiling, particularly next-generation sequencing (NGS), have enabled the identification of recurrent and novel genetic mutations implicated in the pathogenesis of AML. This resulted in refined risk stratification and the development of more effective targeted therapies, like FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors. Over the last years, B-cell lymphoma-2 (BCL-2), a key regulator of the intrinsic apoptotic pathway, has also emerged as a relevant target for therapy for many diseases including AML, and promising results were reported with the use of BCL-2 inhibitors. This article will present an overview of some recent breakthroughs in the field of AML, with a focus on the latest drug approvals in AML. The asses...

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Safety and Efficacy of Cusatuzumab in Combination with Venetoclax and Azacitidine (CVA) in Patients with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Eligible for Intensive Chemotherapy; An Open-Label, Multicenter, Phase 1b Study

Cited by 9 publications

References 0 publications

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

The CD70-CD27 axis in oncology: the new kids on the block

The Evolving Treatment Landscape of AML

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