PracticeUpdate Conference Series ASH 2018

Expedited Genetic Screening Feasible for Detecting Subtypes of AcuteMyeloid Leukemia Rapid turnaround of screening results translates to rapid initiation of the best targeted therapy. G enetic analysis, performed in 7 days or less, can be used to screen patients for particular subtypes of acute mye-

Of the 285 patients whowere diagnosedwith AML, the researchers were able to assign 273 to therapy within 7 calendar days of their samples arriving at the genomic provider, Foundation Medicine. “We’ve achieved our primary endpoint of assigning therapy within 7 days in over 95% of patients,” Dr. Burd said. “What got us to the 7-day turnaround time is mostly by [Foundation Medicine] prioritizing samples and changing the logistical flow of how they come in,” Dr. Burd told Elsevier’s PracticeUpdate . “And also, by a little bit of what I call ‘brute force’ by going to three shifts a day, so they are processing samples 24 hours a day.” “But the technology will continue to advance, and we’ll see timelines improve, and Foundation Medicine is looking to advance it even further to create shorter turnaround times,” she said, adding that next-genera- tion sequencing technology continues to advance at a rapid pace. Overall, 146 patients have moved on to the study’s second phase, in which they are being treated in 1 of 11 clinical trials for experi- mental AML therapies that are targeting their specific AML subtype. In commenting on the clinical significance of being able to turn around this genetic analy- sis within 7 days, Joseph Mikhael, MD, of the International Myeloma Foundation in Phoenix, Arizona, said, “One of the greatest challenges we face in the concept of personalized med- icine is that by the time you determine what is best for a patient with diseases like AML, in a sense the horse is already out of the barn, and you’ve had to start the patient on treat- ment already, or the disease will progress quite rapidly.” He recalled that when he was in training, he would send out genetic evaluations on AML patients and would not obtain results until patients had already completed their first month of therapy. “So, to be able to get these early is so very fundamental,” he said. “And I know the objec- tive is to reduce the timeframe even further, so we can have closer to real in-time results to influence that individual patient.”

loid leukemia (AML) before they have even begun treatment, according to research presented here at ASH 2018. “Acute myeloid leukemia is the most com- monly diagnosed adult leukemia,” said Amy Burd, PhD, of The Leukemia & Lymphoma Society in White Plains, New York, during her presentation of the study, “and it is also the most lethal.” According to the National Cancer Institute, there will be an estimated 19,520 new cases of AML this year, and the 5-year survival rate is 27.4%. The Beat AML Master Trial, led by the Leukemia & Lymphoma Society, is a col- laboration of researchers, pharmaceutical companies, a clinical research organization, and a genomic provider. “We know that it is a heterogeneous disease,” she added. “Coupled with the increasing evi- dence of efficacy for targeted therapy in AML, we hypothesized that we can improve out- comes by matching patients to the increasing numbers of available targeted therapies.” The primary question the trial addresses is whether a personalized therapy based on genomics can be safely assigned to an AML patient. Expediting this kind of genetic analysis so that it is received within 7 days will help doctors match their patients with the ther- apy best suited to their disease as quickly as possible, something which is critical in treating patients with AML. As explained by Dr. Burd, because AML pro- gresses rapidly, physicians prefer not to wait the 2 or 3 weeks it takes to do a genomic analysis before beginning treatment. Therefore, they are likely to start all of their patients on the same treatment regimen until they determine which subtype a patient has. The researchers enrolled 356 patients over 60 years of age with suspected or confirmed AML between 2016 and 2018. Using samples from these patients, the researchers applied three types of genetic analysis techniques – cytogenetics, polymerase chain reaction (PCR), and next-generation sequencing – to create a genetic profile of each patients.

“In this patient population, four cycles of CHOP in combination with six applica- tions of rituximab are equally effective in eradicating the malignant lymphoma clone,” she said. “This conclusion is confirmed by the observation of similar response and, importantly, identical relapse rates.” Although the relapse rates were similar between arms in the trial, Dr. Poeschel said that she was surprised to find that cumulative relapses appeared to be linear during follow-up. Based on the literature, it is expected that 70% of DLBCL relapses will occur within the first year from diagnosis, with a declining rate of relapse thereafter. Thus, Dr. Poeschel cautioned that the “patients relapsing in our trial might have a different biological background” than would be observed in an unselected population of patients with DLBCL. Because the Flyer trial was designed in the pre-PET era, patients included in the trial were not required to undergo an FDG-PET scan. Dr. Poeschel suggested future studies may investigate whether performing an early PET scanmight allow for clinicians to further de-escalate the chemotherapy regimen given to younger, lower-risk DLBCL patients.

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ASH 2018 • PRACTICEUPDATE CONFERENCE SERIES