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New CLL Therapy Showing Promise for AML

LLS-funded researcher Anthony Letai, MD, PhD, talks about how his work led to clinical trials of venetoclax for acute myeloid leukemia (AML) and a priority review by the FDA, and how these developments could ultimately lead to the first new therapy approval for AML in decades.

An associate professor in medicine at the Dana-Farber Cancer Institute, Letai has been the recipient of several LLS grants in recent years – supported as a Fellow and Scholar, and most recently, receiving Translational Research Program funding.

Investigational CLL Therapy to Get Priority Review by FDA

Marking another promising advance for the treatment of patients with chronic lymphocytic leukemia, including those with a rare subset of this blood cancer, the U.S. Food and Drug Administration (FDA) has granted priority review for an investigational compound that has shown positive results in a Phase II clinical trial.

Complications of CLL or CLL Treatment

Infection

People with CLL are more likely to get infections.  

CLL Staging

Doctors use staging to help them predict chronic lymphocytic leukemia's (CLL's) progression and develop an appropriate treatment plan. Two staging systems, the Rai system and the Binet System, have been used throughout the world. In 2016, a new prognostic model called the CLL International Prognostic Index (CLL-IPI) was released, enabling a more targeted management of CLL.

Staging systems for CLL take into account:

Immunotherapeutic Targeting of FCRL1 in CLL

Evolving insights into the B cell-restricted FCRL1 surface protein reveal that it integrates with critical signaling pathways and is a promising immunotherapeutic target in CLL. Based on preclinical evaluation of novel FCRL1 monoclonal antibodies, we propose developing chimeric antigen receptor (CAR) T cells for targeting in unique mouse models and patient-derived cells. The results will form the basis for strategic drug development and clinical testing in CLL and related B cell malignancies.

What is CLL?

#ASH15 Day 3: Big Advances in Treating Chronic Lymphocytic Leukemia

John Byrd, M.D., of the Ohio State University Comprehensive Cancer Center, is one of the world’s renowned scientists in the field of blood cancer. LLS has been supporting his work for the better part of two decades. While Byrd has, of late, turned his attention to the problem of finding better therapies for patients with acute myeloid leukemia (AML), it is in chronic lymphocytic leukemia (CLL) that he has made his mark. 

FDA Approves New Targeted Treatment for CLL/SLL

CLL-1 CAR-T cells and trametinib for the treatment of Ras-mutated CMML and JMML

We hypothesize that demonstrating activity of CLL-1 CAR-T (CLL1CART) cell therapy with or without trametinib in pre-clinical models of chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) is the most efficient method to bring cellular therapy to patients with these orphan diseases. In Aim 1, we will determine the in vitro and vivo efficacy of CAR-T cells redirected against CLL-1 using patient-derived xenograft (PDX) models of CMML and JMML. In Aim 2, we will evaluate the role of combining trametinib with CLL1CART cells.

Clinical and molecular determinants of CLL eradication with targeted combination therapy

The genomic architecture of residual CLL and molecular determinants of disease progression after targeted combination therapy are unknown. In a phase 2 study of zanubrutinib and venetoclax in CLL, I will investigate the depth of response and genomic changes using cellular and circulating tumor DNA. Data generated from this proposal will provide foundational evidence to develop genomic markers for non-invasive monitoring of treatment response and precise prediction of outcome.

Inhibition of PKCβ as a strategy for BTK inhibitor refractory CLL

Patients with CLL that have progressed on BTK inhibitors have high risk disease with few clinical options. Here we propose a novel, selective inhibitor of PKCβ, MS-553, as a strategy for these patients. Our project will evaluate this drug alone and in combination with venetoclax preclinically and will perform correlative studies from an ongoing phase 1/2 trial of this drug alone and in combination with venetoclax.

Reflections from the #ASH19 Meeting

As the 61st Annual ASH (American Society of Hematology) Meeting and Exhibition winds down here in Orlando, here are some thoughts on where things stand in the world of blood cancers.

Chronic Lymphocytic Leukemia (CLL)

BAFF-ligand CAR T-cells and pre-apheresis B cell lymphodepletion for relapsed / refractory CLL

Most CLL patients treated with CAR T-cells that target the CD19 antigen on the cell do not achieve a complete remission. CLL cells express other molecules on their surface; one of them is the receptor for BAFF (BAFF-R), which is highly expressed. We propose a phase I trial investigating LMY-920 for treatment of CLL. LMY-920 is a different type of CAR T-cell because it does not rely on an antibody structure to identify BAFF-R, but uses the structure of the ligand BAFF itself, and this may help avoid resistance to CAR T-cells.

More Updates from #ASCO19: Access, Priorities and Progress

What’s Next in Blood Cancer: Looking Ahead to 2023

The most important blood cancer scientific meeting, the American Society of Hematology (ASH), is held every December.

Spotlight on Chronic Lymphocytic Leukemia (CLL)

NHL & CLL Diagnosis and Treatment Update

Update On Chronic Lymphocytic Leukemia (CLL)

CLL: Navigating Treatment with BTK Inhibitors

Living With Chronic Lymphocytic Leukemia (CLL)

The Future of CLL Treatment: What’s Next?