58th ASH Annual Meeting & Exposition

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The 58th American Society of Hematology Meeting & Exposition took place over the 3rd – 6th December. We were delighted to be able to support Carmela Ciardullo with a Bright Red travel grant.

Carmela is a Research Associate at the Northern Insitute for Cancer Research, and was invited to present her abstract focusing on Chronic Lymphocytic Leukaemia.

Carmela said “ASH 2016 was an invaluable experience with thousands of delegates attending and numerous high quality oral and poster presentations. The excellent education program provided an opportunity to learn about research outside my normal field of interest and the scientific committee sessions as always provided up to the minute insights into a range of topics.

Of particular interest to me were both oral and poster presentations regarding novel MDM2 antagonists as a treatment options for patients with haematological malignancies. Christian Klein from Roche Innovation Center Zurich discussed their preclinical data demonstrating a strong anti-tumoral efficacy of combining the CD20 antibody obinutuzumab with the Bcl-2 inhibitor venetoclax and the MDM2 inhibitor RG7388. Their data showed that the triple combination of obinutuzumab with venetoclax and RG7388 can further improve outcome in two preclinical human wildtype p53 NHL tumor xenograft models, in particular regarding complete tumor remissions and long term response, and support the clinical investigation of this triple combination for the treatment of B cell malignancies.

Another study by William Pierceall showed that multiparametric flow cytometry MRD assessment is an early indication aligning with cCR in relapsed/refractory AML patients treated with RG7388. Further, assessment for association with progression-free survival indicated that the lowest quartile patients by MRD flow cytometry measurement (<1%) are likely to exhibit a pronounced survival benefit over those patients with higher detectable levels of MRD (>1%). As such, the data presented support inclusion of MRD assessment by flow cytometry as a prognostic indicator to provide guiding information for assignment of depth of AML patient response. This biomarker for diagnostic potential and prognostic indicator of survival-based outcomes should be monitored in future randomized clinical studies of RG7388.

Another study from MD Anderson Cancer Center reported the initial results of a Phase I trial aimed at characterizing the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles and preliminary efficacy of the MDM2 antagonist DS3032b in in patients with hematological malignancies.

However, a clinical challenge is that not all the tumors bearing wild-type TP53 are sensitive to MDM2 inhibition. In this respect, a group from MDM Anderson Cancer Center discovered novel gene profiling-based algorithms for predicting tumor sensitivity to MDM2 inhibition using DS-3032b, a novel potent MDM2 inhibitor, which is currently in early clinical trials.

Of particular interest to me were the presentations regarding novel treatment options for patients with chronic lymphocytic leukemia, as well as the numerous updates on CLL genomics and epigenomics. I also had the amazing opportunity to present my abstract entitled “The p53-MDM2 Antagonist RG7388 Activates p53 and Induces a Predominantly Pro-Apoptotic Gene Expression Signature in Chronic Lymphocytic Leukemia” and I had useful and positive feedback.

Overall ASH 2016 was an excellent experience. Many thanks to Bright Red for the Travel Award and for supporting my participation to this meeting.”

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