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.
New targeted therapies approved in just the past two years alone are making precision medicine more of a reality for acute myeloid leukemia (AML). As I noted in a previous blog our own Amy Burd, Ph.D., LLS vice president of research strategy, presented compelling data that precision medicine, giving a patient a drug based on their molecular profile rather than one-size fits all, is bringing a paradigm change in how AML patients will be treated moving forward.
For patients with chronic lymphocytic leukemia (CLL), we’re seeing a decided shift toward chemo-free combinations of targeted medicines, opening a debate about whether the old standard, chemotherapy plus an antibody, will be replaced by a new regimen. Studies are showing that combinations of targeted therapies that work by blocking the activity of bad-acting genes, proteins or cellular pathways are quickly pushing their way to the front of the line for treatment of CLL. One study presented at the meeting showed that two targeted oral therapies given together, venetoclax and ibrutinib, resulted in deep remissions for CLL patients, with 75% having high rates of undetectable minimal residual disease, meaning no traces of cancer cells could be found with highly sensitive tests. LLS didn’t fund this study, but has invested millions over two decades to advance both of these therapies.
Further, with the advent of CAR T-cell immunotherapy and bispecific antibodies, both once the stuff of science fiction but now increasingly becoming mainstays of treatment with remarkable results, it’s clear we are experiencing a seismic shift in the standard of care for many patients with leukemia, lymphoma and myeloma.
Since coming on the scene, CAR-T has emerged as a miracle treatment that has brought patients from the brink of death to enduring remissions. But CAR-T doesn’t work for everyone and even many patients who initially respond, can relapse.
Enter mosunetuzumab. This new investigational drug is considered so game-changing for patients whose lymphoma has returned following treatment that it was featured during the plenary session, held in the biggest hall in the conference center to accommodate thousands of attendees. Mosunetuzumab is a bispecific antibody, meaning it binds two proteins, one on the surface of tumor cells (CD20) and the other on the surface of the recipient’s T cells (CD3).
The data presented in the plenary showed that of 124 patients with fast moving, aggressive lymphomas, 46 patients (37%) saw a decrease in the amount of cancer, with 24 (19%) achieving complete remission. Those with less aggressive disease still saw results; a reduction of disease was seen in 42 patients (63%), with 29 (43%) achieving complete remission as well. Among 18 patients whose lymphoma progressed after treatment with CAR-T, 22% experienced complete remissions. The remissions for these patients appear to be long-lasting.
The Leukemia & Lymphoma Society (LLS) launched our Beat AML® master clinical trial in 2016 to revolutionize how we treat patients with acute myeloid leukemia. After forty years of basically doing the same thing and treating AML patients with a one-size-fits-all approach despite it being a disease of multiple subtypes, it was time to try something new. Our study is testing multiple drugs simultaneously at 16 cancer centers around the U.S., using genomic technology to give AML patients the option to try a therapy that has a better chance of working for the specific mutation driving their diagnosis.
We are here in Orlando at the 61st ASH Annual Meeting, and yesterday Amy Burd, Ph.D., vice president of research strategy for LLS, presented an update from the Beat AML trial. The key takeaway: patients on the trial generally do better than patients who opt for standard chemotherapy.
According to Dr. Burd: “We have demonstrated that a precision medicine approach to assigning treatment within seven days is feasible and safe. Patients who elected the assigned treatment had a lower early death rate and superior overall survival compared to patients who elected standard of care. The data suggests that this umbrella approach has the potential to improve both short and long term outcomes in AM, and sets the stage for a precision medicine approach in other blood cancers.”
More AML News
Much discussion here at #ASH19 is focused on a drug called venetoclax, considered by many to be a game-changer for many forms of blood cancer. LLS has supported advances in venetoclax over the past two decades, helping to lead to its approval for chronic lymphocytic leukemia. The U.S. Food and Drug Administration approved it in 2018 for AML. Multiple studies presented at the meeting examine venetoclax in combination with other therapies for a variety of blood cancers, including AML.
One study by a team from University of Colorado, including Craig Jordan, MD, who leads a $5 million Specialized Center of Research grant from LLS, looks at why some patients with AML are resistant to venetoclax. Recent clinical trials report that more than 70% of previously untreated older AML patients respond to the combination of venetoclax with the chemotherapy azaciticine, but a subset of AML patients do not respond. The team’s study shows that AML patients with a prevalence of a type of white blood cell called a monocyte do not respond to this combination and clearly new strategies are needed for this subset of patients.
After a 40 year drought in new therapies for AML, several new drugs that target specific mutations were approved by the FDA from 2017 to 2019, potentially improving outcomes for certain subsets of AML patients. However, more novel targets are still needed. LLS-funded researcher, Xiangguo Shi, Ph.D., of Baylor College of Medicine, is presenting a study Monday at the ASH meeting discussing the role of a gene called NMNAT1 (nicotinamide nucleotide adenylyltransferase 1) in AML. The study shows that developing drugs that inhibit this gene’s activity warrant further consideration.
It’s that time of year again, when more than 30,000 scientists specializing in blood cancers and other blood disorders, oncologists and hematologists, pharmaceutical and biotechnology company representatives, and cancer patient advocacy organizations gather in one place to learn about the latest progress in treatments and share new ideas.
This year, we’re in sunny Orlando for the 61st ASH (American Society of Hematology) Annual meeting and Exposition.
Today (Saturday) was the first official day, and there is already much to talk about, but first The Leukemia & Lymphoma Society (LLS) raised the curtain on Friday with several LLS-hosted programs.