Beat AML in the Time of COVID-19: A Powerful New Video
Like many clinical trials across the U.S. and the globe, The Leukemia & Lymphoma’s Beat AML Master Trial has been dramatically impacted by the COVID-19 pandemic and has had to make adjustments to continue to provide critical treatment to patients who were previously enrolled.
A Groundbreaking Trial
LLS has been leading this first-of-its kind collaboration since 2016 to simultaneously test multiple treatments for patients with acute myeloid leukemia. The Beat AML Master Trial was launched to address the 40-year practice of treating all patients with the same combination of chemotherapies which simply doesn’t work for many, especially older patients for whom the drugs are highly toxic.
AML is a fast-moving disease with multiple subtypes that needs to be treated quickly once diagnosed; using advanced technology we’ve shown we can rapidly analyze an AML patient’s genetics to identify the mutation driving their subtype of cancer. In Beat AML we’ve shown we can turn around the genetic analysis within an unprecedented seven days and safely make a treatment decision about the right therapy for the right patient.
To date, we’ve screened more than 900 patients, with many of them going on to receive a targeted treatment at one of the 16 cancer centers around the country hosting the trial.
Data shows that patients who were part of the Beat AML study had a lower early mortality compared to patients who elected standard of care, and superior overall survival. In one sub-study, patients’ median survival was 12.8 months vs. 3.9 months for patients with standard of care
Beat AML has set stage for how clinical trials using a precision medicine approach can be done in blood cancers in the future. The trial is changing the paradigm for how AML is treated using a precision medicine approach.
The Leukemia & Lymphoma Society (LLS) congratulates Carl June, MD, of the University of Pennsylvania, whose groundbreaking research ushered in a new era in cancer immunotherapy, for his election into the U.S. National Academy of Science (U.S. NAS). Dr. June earned this prestigious honor through recognition by his peers for his “distinguished and continuing achievements in original research.”
LLS is a long-time, proud supporter of Dr. June, whose innovative research pioneered the advancement of chimeric antigen receptor (CAR) T-cell therapy, a first-of-its-kind personalized cellular therapy for cancer that engineers a patient’s own immune cells to fight their cancer. The treatment first received FDA approval in August 2017, and approval for additional indications in 2018.
Dr. June is part of a class of more than 140 new inductees from around the world who have been elected to this elite groups group of nearly 2,900 members around the world. The U.S. NAS is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and—with the National Academy of Engineering and the National Academy of Medicine—provides science, engineering, and health policy advice to the federal government and other organizations.
CAR-T has been a game-changer, maybe even a cure, for many patients with certain types of leukemia and lymphoma who have failed multiple prior therapies. Scores of adults and children who were near death are now in remission, and some remain healthy more than five years after treatment.
LLS has been funding Dr. June and his team for more than two decades, an investment exceeding $20 million, supporting his efforts to harness the power of T cells to fight cancer. And we continue to support his work through a recently-awarded Specialized Center of Research grant to expand the use of CAR-T for use in other types of blood cancers.
Overall, LLS has invested more than $90 million in adoptive cellular therapy research, and $50 million into CAR T-cell therapies in particular. LLS is also supporting the next-generation of CAR-T by supporting Dr. June and many other researchers performing advancing novel approaches to make CAR T-cell therapy even more effective and useful for more patients.
Carl June’s pioneering work in CAR-T is now opening the door to a critical new area of study: finding a treatment for patients with COVID-19. Dr. June, who himself was stricken with the virus for three weeks but now recovered, is applying knowledge he acquired while treating patients with CAR-T to address the dangerous symptoms experienced by many COVID-19 patients. An extreme immune response called cytokine storm syndrome is experienced by most patients treated with CAR-T, and June and his team identified a treatment to mitigate the condition. It turns out COVID-19 patients also experience cytokine storm syndrome, so they are testing the same treatment for these patients.
In February 2020, LLS honored Dr. June at its Seventh Annual Red & White Ball in Philadelphia, hosted by our Eastern Pennsylvania Chapter, presenting him with the prestigious Robert de Villiers Spiral of Life Award in front of 600 attendees. The following video features Dr. June and survivor, Doug Olsen, who discusses the experience of being one of the original CAR-T patients. Click here to view the video.
The American Association of Clinical Research, like so many other organizations, was forced to move its major annual meeting from sunny San Diego to a virtual format this past week in response to the COVID-19 pandemic. AACR made the decision to host the meeting on a virtual platform over two days to give scientists an opportunity to present their latest discoveries across the spectrum of cancer research.
Several presentations relevant to the blood cancers drew my interest.
Off-the-shelf CAR-T
It’s no surprise that the revolutionary immunotherapy, chimeric antigen receptor (CAR) T-cell therapy, continues to attract significant attention at cancer conferences. The treatment has given thousands of very ill patients who had exhausted all existing options a new shot at life, maybe even a cure, by harnessing their own engineered T cells to fight the cancer.
LLS has played a significant role in funding the discovery and advancement of CAR-T.
But since its first approval in 2017 for acute leukemia, followed by approvals for large B-cell lymphomas, the therapy has yet to receive FDA approvals for other cancers. FDA decisions are nearing for several other types of blood cancers, including mantle cell lymphoma and myeloma.
CAR-T is a costly, time-consuming procedure, as the CAR-Ts have to be engineered from each patient’s own cells. Developing pre-made “off-the-shelf” CAR-Ts would shave weeks off the manufacturing time, delivering a faster, more affordable option.
But using donor cells has challenges as the donor immune cells can attack the patient’s own cells – a life-threatening condition called graft v. host disease (GVHD).
A group from China presented their approach to this off-the-shelf CAR-T during the AACR meeting. The study was in a small group of patients with a very difficult to treat leukemia, called T-cell acute lymphoblastic leukemia (T-ALL), which has a very poor prognosis. The CAR T-cell therapy - TruUCAR GC027- induced encouraging early response rates in four of the five patients in the study. The team used a gene editing process called CRISPR/CAS9 to modify the protein responsible for causing GVHD.
While LLS did not support the study presented, an LLS-research funded team at Baylor College of Medicine is conducting similar research. Maksim Mamonkin, Ph.D., who leads the team at at Baylor, was the first researcher to show that CAR-Ts targeting the CD7 protein commonly found on the surface of T-ALL has the potential to treat this deadly disease. Like the Chinese group, his team is also attempting to develop an off-the shelf version. LLS is supporting multiple other projects developing off-the-shelf CAR-Ts – potentially bringing on the next wave in this revolutionary treatment.
Glimmer of Hope for a vexing disease
Another exciting study presented at AACR had many connections to LLS-funded research. LLS has long supported research to address a genetic mutation – the MLL1 fusion protein – associated with a very deadly form of leukemia called mixed lineage leukemia – rearranged (MLL-r). Sustained LLS-supported research at University of Michigan, led by Jolanta Grembecka, Ph.D., was key to the discoveries presented at AACR by a company called Syndax.
The study was small - only six patients, with two of them responding, one with a complete remission, and another with a partial response. This might seem like a small victory, but the fact is, this disease has long been considered “undruggable.” Clearly, more study is warranted in this approach. LLS is also supporting research in MLL inhibitors in patients with acute myeloid leukemia at other institutions.
Blood cancer therapies for COVID-19
As the topic of COVID-19 is unavoidable in these frightening days, it was also a subject of study and discussion at the AACR meeting.
Not surprisingly, several studies out of China, where the virus first emerged, and Italy, also hit hard by the pandemic, noted that cancer patients infected with the COVID-19 virus are at greater risk of getting very sick. In fact, one study showed that cancer patients are two to three times more likely to die than cancer-free individuals with the novel coronavirus.
One of the most deadly symptoms of the virus is a very intense, often fatal immune response that attacks the respiratory system and other organs of the body. Researchers presenting at the AACR conference, as well as many researchers supported by LLS, are investigating the use of therapies used to treat blood cancer patients to treat the COVID-19 patients.
One very dangerous immune response, called the cytokine release syndrome, is well-known among researchers who treat blood cancer patients with CAR-T. The same therapy used to mitigate CRS in CAR-T patients is now being tested in COVID-19 patients. Other therapies approved for blood cancer patients, including ruxolitinib, that treats patients with a blood malignancy called myeloproliferative neoplasms, and several BTK-inhibitors approved for chronic lymphocytic leukemia and mantle cell lymphoma, are also being investigated to treat COVID-19.
AACR will hold the second portion of its virtual meeting June 22-24. American Society of Clinical Oncology (ASCO), which holds the world’s largest cancer conference annually in Chicago in early June, is also moving to the virtual platform. I’ll be following along with these conferences as well, so stay tuned….
