A phase II study of omacetaxine mepesuccinate for patients with higher‐risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents

Short, Nicholas J.; Jabbour, Elias; Naqvi, Kiran; Patel, Ami; Ning, Jing; Sasaki, Koji; Nogueras‐González, Graciela M.; Bose, Prithviraj; Kornblau, Steven M.; Takahashi, Koichi; Andreeff, Michael; Sanchez‐Petitto, Gabriela; Estrov, Zeev; DiNardo, Courtney D.; Montalban‐Bravo, Guillermo; Konopleva, Marina; Alvarado, Yesid; Bhalla, Kapil N.; Fiskus, Warren; Khouri, Maria; Islam, Rubiul; Kantarjian, Hagop M.

doi:10.1002/ajh.25318

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…The discovery and d e v e l o p m e n t o f H H T a n d r e l a t e d c o m p o u n d s i s comprehensively reviewed by Itokawa et al (Itokawa et al, 2005). A semi-synthetic version of HHT, also known as omacetaxine mepesuccinate, has been reported to be an effective treatment for myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) in patients with resistance and intolerance toward hypomethylating agents such as azacitidine and decitabine (Short et al, 2019).…”

Section: Other Plant-derived Anticancer Agentsmentioning

confidence: 99%

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

et al. 2020

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Cancer is a severe health problem that continues to be a leading cause of death worldwide. Increasing knowledge of the molecular mechanisms underlying cancer progression has led to the development of a vast number of anticancer drugs. However, the use of chemically synthesized drugs has not significantly improved the overall survival rate over the past few decades. As a result, new strategies and novel chemoprevention agents are needed to complement current cancer therapies to improve efficiency. Naturally occurring compounds from plants known as phytochemicals, serve as vital resources for novel drugs and are also sources for cancer therapy. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, and podophyllotoxin analogs. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancer. The specific mechanisms include increasing antioxidant status, carcinogen inactivation, inhibiting proliferation, induction of cell cycle arrest and apoptosis; and regulation of the immune system. The primary objective of this review is to describe what we know to date of the active compounds in the natural products, along with their pharmacologic action and molecular or specific targets. Recent trends and gaps in phytochemical based anticancer drug discovery are also explored. The authors wish to expand the phytochemical research area not only for their scientific soundness but also for their potential druggability. Hence, the emphasis is given to information about anticancer phytochemicals which are evaluated at preclinical and clinical level.

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Section: Other Plant-derived Anticancer Agentsmentioning

confidence: 99%

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

et al. 2020

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“…This was observed with lenalidomide added back into treatment in patients who had lost response to azacitidine. 80 The same rationale is at the basis of recent studies combining HMAs with various agents possessing different mechanisms of action, [81][82][83] but results have not been encouraging. 84…”

Section: Add-on Strategymentioning

confidence: 99%

How I treat MDS after hypomethylating agent failure

Santini

2019

Blood

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Hypomethylating agents (HMA) azacitidine and decitabine are standard of care for myelodysplastic syndrome (MDS). Response to these agents occurs in ∼50% of treated patients, and duration of response, although variable, is transient. Prediction of response to HMAs is possible with clinical and molecular parameters, but alternative approved treatments are not available, and in the case of HMA failure, there are no standard therapeutic opportunities. It is important to develop a reasoned choice of therapy after HMA failure. This choice should be based on evaluation of type of resistance (primary vs secondary, progression of disease [acute leukemia or higher risk MDS] vs absence of hematological improvement) as well as on molecular and cytogenetic characteristics reassessed at the moment of HMA failure. Rescue strategies may include stem-cell transplantation, which remains the only curative option, and chemotherapy, both of which are feasible in only a minority of cases, and experimental agents. Patients experiencing HMA failure should be recruited to clinical experimental trials as often as possible. Several novel agents with different mechanisms of action are currently being tested in this setting. Drugs targeting molecular alterations (IDH2 mutations, spliceosome gene mutations) or altered signaling pathways (BCL2 inhibitors) seem to be the most promising.

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“…Advances in lower-intensity therapy in combination with targeted therapies, such as Menin inhibitors in patients with KMT2A rearrangements and NPM1 mutations, may lead to improved outcomes [ 56 , 57 , 58 , 59 ]. Additionally, improvements in the treatment of MDS with lower-intensity therapy will prevent disease progression and improve patient outcomes [ 26 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ].…”

Section: Intensive Chemotherapy Versus Low-intensity Chemotherapymentioning

confidence: 99%

Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities

Oshikawa

Sasaki

2023

Cancers

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Traditionally, the goal of AML therapy has been to induce remission through intensive chemotherapy, maintain long-term remission using consolidation therapy, and achieve higher rates of a cure by allogeneic transplantation in patients with a poor prognosis. However, for the elderly patients and those with comorbidities, the toxicity often surpasses the therapeutic benefits of intensive chemotherapy. Consequently, low-intensity therapies, such as the combination of a hypomethylating agent with venetoclax, have emerged as promising treatment options for elderly patients. Given the rise of low-intensity therapies as the leading treatment option for the elderly, it is increasingly important to consider patients’ age and comorbidities when selecting a treatment option. The recently proposed comorbidity-based risk stratification for AML allows prognosis stratification not only in patients undergoing intensive chemotherapy, but also in those receiving low-intensity chemotherapy. Optimizing treatment intensity based on such risk stratification is anticipated to balance treatment efficacy and safety, and will ultimately improve the life expectancy for patients with AML.

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A phase II study of omacetaxine mepesuccinate for patients with higher‐risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents

Cited by 11 publications

References 23 publications

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

How I treat MDS after hypomethylating agent failure

Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities

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