Acute Myeloid Leukemia: LSD1 Inhibition In Combination With Azacitidine in the Elderly

MedicalResearch.com Interview with:

Dr Carlos Buesa

Dr Buesa

Dr. Carlos Buesa PhD
Chief Executive Officer
Oryzon Genomics 

MedicalResearch.com: What is the background for this study?

Response: Lysine specific demethylase 1 (LSD1, also known as KDM1A) is a histone modifying enzyme that removes methyl groups, thereby regulates the expression of many genes important in cancer progression and cell proliferation.

Aberrant expression of LSD1 has been shown in many types of cancers. In particular, LSD1 expression is upregulated in bladder, small cell lung (SCLC), and colorectal clinical cancer tissues when compared with the corresponding nonneoplastic tissues. LSD1 has also been shown to be overexpressed in some breast cancers and may function as a biomarker of the aggressiveness of the disease.

However, the function of LSD1 is most understood in acute leukemia, particularly Acute Myeloid Leukemia and Acute Lymphoblastic leukemia. LSD1 is crucial for the function and maintenance of the leukemic stem cells, a subset of malignant cells that is believed to be the ultimate reason for relapse in these patients. LSD1 inhibition might be a therapeutic solution to avoid those relapses.

MedicalResearch.com: What are the main findings?

Response: Data presented at the 24th Congress of the European Hematology Association (EHA-2019) in Amsterdam, showed that the combination of iadademstat with azacitidine demonstrated a good safety profile in the first six patients who completed treatment in Part 1 of the Phase II ALICE study. The full target engagement at this initial planned dose allowed us to determine the recommended dose of iadademstat for Part 2 of this Phase II trial (90 ug/m2). The preliminary clinical efficacy results are also positive. The drug produces a clear differentiation effect in the blasts of patients and the clinical efficacy responses are encouraging, with 80% of objective responses in the five patients who were evaluable.

Of these, 75% were complete remissions with incomplete hematologic recovery (CRi) and 25% were partial remissions (PR) (3/5 CRi and 1/5 PR). Interestingly, the observed clinical responses appear rapidly with a median time of 1.5 months.

MedicalResearch.com: What should readers take away from your report? 

Response: Although the total number of patients is still small to date, the results are promising and suggest continued development. In particular, we want to highlight the high percentage of complete remissions, the quick onset of response, and the tolerability of the combination with azacitidine.

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: The data presented suggest continued development of iadademstat, which we believe has a powerful differentiating effect in hematologic cancers. Further phase 2 data from the ALICE study will be presented later in the year at the ASH conference.

We are also evaluating a second combination of iadademstat, with platinum/etoposide, in second line SCLC patients (CLEPSIDRA study). Initial preliminary efficacy data from this Phase II study is expected September 2019. 

Citation:

24th Annual Congress of the European Hematology Association, June 13-16, Amsterdam, Netherlands

https://library.ehaweb.org/eha/2019/24th/266077/carlos.buesa.alice.an.aml.study.with.lsd1.inhibition.in.combination.with.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Diadademstat 

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