The annual meeting of the American Society of Hematology (ASH) brings together leaders from around the world who treat people with blood cancers and other blood disorders. Doctors and researchers from Memorial Sloan Kettering presented their research at the meeting, held this year in Orlando. Below are some highlights from the past few days.
CAR T and Stem Cell Transplants
Chimeric antigen receptor (CAR) T cell therapies have been in the spotlight at the ASH meeting. Many scientists in the field are excited by the prospect of using the genome-editing tool CRISPR to engineer more-potent CAR T cells.
At MSK, researchers Michel Sadelain, Renier Brentjens, and Isabelle Rivière and their colleagues are at the forefront of CAR T science. Just last year, the team published results from the longest-running clinical trial of CAR therapy, showing which patients benefitted most. This year at ASH, another member of that team, MSK medical oncologist Jae Park, presented the results of a retrospective study that provides clues into who may benefit most from a stem cell transplant following CAR therapy.
A stem cell transplant replaces a person’s blood-forming stem cells with those from a donor. It can be a cure for some people with cancer, yet it comes with serious potential risks, such as life-threatening infections and graft-versus-host disease. Previous research from Dr. Park and his colleagues had suggested that there was no clear survival advantage to a stem cell transplant in adults with acute lymphoblastic leukemia (ALL) who were treated with CAR T cells. But the scientists were curious to find out if a group of patients would benefit from the procedure.
Of 53 adults with ALL who received CAR T cells at MSK, 16 of those who had a complete response to the CAR therapy went on to have a stem cell transplant. Dr. Park and his colleagues looked for correlations between how well these patients did and several variables: age, a prior stem cell transplant, the presence of the Philadelphia chromosome, the amount of disease measurable at the time of the CAR therapy, the severity of cytokine release syndrome, and neurotoxicity.
The only variables that seemed to make a difference were age and neurotoxicity. Specifically, being younger and having no severe neurotoxicity during CAR therapy were associated with improved overall survival following a stem cell transplant. Dr. Park cautioned that the small size of the study limits drawing firm conclusions. Nevertheless, the results point to a group of people for whom the potential benefits of a stem cell transplant may outweigh the risks. Further research is needed.Back to top
Advances in CLL
MSK hematologist-oncologist Anthony Mato presented the results of several studies aimed at improving care for people with chronic lymphocytic leukemia (CLL). One study dealt with identifying the best treatment options for people with CLL who have had to stop taking the targeted drug venetoclax (Venclexta®). Dr. Mato and colleagues conducted a retrospective study of 326 people with CLL from around the world who received venetoclax and then switched to another drug.
They looked at how well these people did on various treatments — specifically BTK inhibitors, PI3K inhibitors, CAR T therapy, and stem cell transplantation. Of these, they found that BTK inhibitors were an effective post-venetoclax treatment, provided the patients had not yet received BTK inhibitors or had not developed resistance to these drugs. They also found that a stem cell transplant was a good option that provided lasting benefits.
In a second presentation, Dr. Mato discussed the results of a first-in-human trial of a BTK inhibitor called LOXO-305. This targeted drug works differently than existing BTK inhibitors. The trial, which enrolled 13 people, showed that LOXO-305 was safe. It also provided proof of concept that this approach may be effective at helping people with CLL and other B cell cancers, including those who have developed resistance to existing BTK inhibitors.
Finally, Dr. Mato discussed results from a study that tested a combination of targeted drugs given at lower dosages to people with CLL. Combination approaches have the potential to preempt the emergence of drug resistance but are often too toxic when each drug is given at full strength.
The phase I study tested a lower-dose combination of the BTK inhibitor everolimus (Afinitor®, Zortress®) and pomalidomide (Pomalyst®). It included 33 people with CLL and lymphoma who lacked an approved treatment option. Dr. Mato and his colleagues found that this combination, named DTRM-555, was generally safe and showed signs of effectiveness in several people. A phase II study of the combination is underway.
“Together, these studies show the progress we at MSK are making in developing much-needed therapies for people with CLL,” Dr. Mato says.Back to top
Blood Clots and Cancer
Blood clots are a life-threatening side effect in people being treated for cancer. Known risk factors for blood clots include cancer type and stage, obesity, blood cell counts, and treatment with chemotherapy. However, it is still difficult for doctors to predict the risk of blood clots in individual people.
To find out if a tumor’s molecular profile could predict the risk of blood clots, MSK hematologist Simon Mantha and colleagues conducted a study in which they analyzed tumor DNA sequences for 341 genes in 11,695 people with cancer.
As Dr. Mantha presented at the ASH meeting, the scientists found that mutations in several genes — STK11, MET, KEAP1, CTNNB1, and KRAS — increase the risk of blood clots in people with cancer.
Dr. Mantha hopes these findings will ultimately translate into better methods to predict who is most at risk for this dangerous complication.Back to top