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Rapid assignment of molecularly driven treatment feasible for acute myeloid leukemia
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SAN DIEGO — Clinicians used genetic information to match patients with acute myeloid leukemia to molecularly targeted therapies within a week of diagnosis, according to findings from the BEAT-AML study presented at ASH Annual Meeting and Exposition.
“[AML] is the most lethal adult leukemia,” Amy Burd, PhD, vice president of research strategy for the Leukemia and Lymphoma Society, said during a press conference. “It is a heterogeneous disease. We evaluated whether we could improve patient outcomes by matching patients to the appropriate therapy.”
Burd and colleagues and colleagues aimed to determine whether they could use genetic profiling to assign patients to molecularly defined, subtype-specific therapies within 7 days of diagnosis, and whether that treatment would be effective.
The analysis included 285 newly diagnosed patients aged older than 60 years (median age, 72 years; 58.6% men) with AML from 12 clinical sites.
Eligible participants were genetically screened at the point of entry with “broad and simple” criteria, Burd said.
Criteria used to determine AML subtypes and matching therapies included:
- core binding factor (1.4%; samalizumab [ALXN 6000, Alexion Pharmaceuticals] plus induction);
- NPM1 and FLT3-IDT mutation (13%; entospletinib [GS-9973, Gilead Sciences] plus induction for fit patients, or as monotherapy for unfit patients);
- mixed-lineage leukemia rearrangements (2.1%; entospletinib plus azacitidine);
- IDH2 mutation (11.2%; enasidenib [Idhifa; Celgene, Agios] plus azacitidine);
- IDH1 mutation (5.3% ivosidenib [Tibsovo, Agios] plus azacitidine);
- TP53 mutation (19.3%; entospletinib plus decitabine, or pevonedistat [MLN-4924, Millennium/Takeda] plus azacitidine);
- wild-type TP53 with complex karyotype (8%; entospletinib plus decitabine);
- FLT3 mutation (6.7%; gilteritinib [Xospata, Astellas] monotherapy or plus decitabine);
- TET2 and WT1 mutations (11.9%; BI 836858 [Boehringer Ingelheim] plus azacitidine); and
- marker-negative status (21.2%; BI 836858 [Boehringer Ingelheim] plus azacitidine).
Researchers used a variant allele frequently of at least 0.3 to determine the dominant clone. If that did not exist, the treatment algorithm used a variant allele frequency of at least 0.2.
“Given the heterogeneity of the disease, we used this algorithm to make our treatment assignments,” Burd said. “Ultimately, teatment assignments are made based on what’s best for the patient, even if that assignment is outside of the BEAT-AML study.”
Overall, 273 patients (95.8%) underwent treatment within 7 days.
“The answer to the question of can we assign using genomic information within 7 days is, yes,” Burd said. “We have achieved our primary endpoint.”
Thus far, 146 patients have been treated, whereas 139 (48.8%) were not treated. Most of those not treated chose standard of care (20%) or other therapies (before trial assignment, 7%; after trial assignment, 8.1%). Other reasons for lack of trial treatment included death during the 7 days (2.5%), palliative care (8.1%) or not specified (2.1%).
“The majority of patients will go on to therapy, and this will increase as we have more studies,” Burd said.
More studies using this protocol are ongoing and opening, according to Burd.
“I think the future of treatment for AML will include point-of-care screening to determine what type of AML the patient has and then make the treatment decision based on that information,” she said in a press release. “Being able to do genetic screening rapidly and efficiently is critical to making a decision for that patient within 7 days. This study demonstrates that the precision medicine approach is feasible and effective.” – by Rob Volansky
Reference:
Burd A, et al. Abstract 559. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.
Disclosures : Burd reports receiving research funding from Acerta and Pharmacyclics, and honoraria from Acerta and Jazz. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Joseph N. Mikhael, MD
One of the greatest challenges we faced in the concept of personalized medicine is by the time you have determined what is best for that patient for diseases like AML — to be blunt — the horse is already out of the barn. You had to have started the patient on treatment already, or else their disease could have progressed quite rapidly. In general, for many of these conditions, we have a bit of a grace period of a few days. Often, it takes a day or several hours to obtain a bone marrow result to even ensure that the patient has the disease. Trying to reduce that window within 7 days is so important. That’s why we wanted to highlight the rapidity of the work of the BEAT-AML study.
Whether it’s with genomic evaluations or the kind of evaluations done in the BEAT-AML study, we’ve seen we can come up with those answers more quickly when there is enhanced collaboration and the expertise of artificial intelligence.
In some previous advanced genomic studies, we would send off the cytotoxic evaluations for a patient with AML and get the result when the patient has already finished their first month of therapy. To be able to obtain them early is so fundamental. I know their objective is to shorten that time frame even further so that we can have closer to real, in-time results to influence the individual patient.
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