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Shifting the Treatment Paradigm in Blood Cancers: New Insights

For decades, the approach to treating diseases like acute leukemia, lymphoma, and myeloma was based on assigning patients to prognostic groups and making uniform treatment decisions within that group. But with comprehensive genomic profiling, we can begin to unravel the heterogeneity within each group and develop more effective treatments for each individual.

We are already seeing the benefits of this approach. For example, acute myeloid leukemia (AML) is particularly complex to treat, especially for older patients (>60 years old) who have a particularly poor prognosis. After 40 years of no change in standard of care, novel targeted therapies have been emerging at a rapid pace in recent years. Nine new targeted therapies for AML have been approved by the FDA in past two years – a sure sign of progress. Still, these therapies are not suitable for all patients – other approaches are needed.

In conjunction with The Leukemia & Lymphoma Society, we are excited to present new advances in the treatment of AML at the American Society of Hematology (ASH) Annual Meeting in San Diego, CA.

In October 2016, The Leukemia & Lymphoma Society announced a landmark master trial to advance the treatment of elderly patients with newly diagnosed AML using a precision medicine approach that identifies specific genomic alterations in these patients and matches them with novel investigational agents. We are proud to be the genomic sequencing partner in this effort. Patients are profiled and assigned to a treatment arm within seven days – a novel approach in itself, as patients have historically been treated almost immediately after diagnosis with little opportunity to obtain genomic sequencing information to guide therapy.

In the initial report of this study being presented at ASH, 95.2 percent (200/210) of patients with AML were successfully assigned to treatment within seven days, confirming the feasibility of this approach, and changing the standard paradigm of the time between diagnosis and treatment. Of those, 52.4 percent (110/210) received treatment through one of the sub-study arms.

One of these sub-studies assesses the efficacy of the oral IDH2 inhibitor, enasidenib, in patients with previously untreated IDH2-mutant AML and has completed Phase II enrollment. Results from this study demonstrated significant clinical activity of enasidenib with achievement of complete response or complete remission with incomplete blood count recovery in 43 percent of patients. In conjunction with a promising safety profile, these findings provide support for further pursuit of the single agent enasidenib or novel combination strategies in the management of these patients.

Data from another sub-study are also being presented on the combination of an anti-CD33 antibody with chemotherapy, and also showed promising efficacy and safety across different patient populations.

We are excited to be part of such a groundbreaking effort that has enormous potential to change the treatment landscape of AML as it is a landscape in much need of change.

Precision medicine also continues to impact care in other acute leukemias beyond AML. We recently published a study in The Oncologist using FoundationOne®Heme to identify a subset of B-acute lymphoblastic leukemia (B-ALL) known as BCR-ABL1-like B-ALL.1 This type of B-ALL is found across all age groups and is associated with a poor prognosis. Unfortunately, the gold standard for definitive identification of such patients is gene expression profiling which is not widely available in routine clinical practice. In this study, we explored whether FoundationOne Heme might alternatively be able to identify these patients.

FoundationOne Heme, which interrogates 406 genes through DNA sequencing and 265 genes through RNA sequencing, was used to profile 450 patients. The testing revealed a wide range of genomic alterations which were consistent with classification of BCR-ABL1-like B-ALL in 29 percent of cases, supporting the ability of this test to serve as a clinically available alternative for identifying a subset of these patients. Accurate identification can help make more informed decisions, and ultimately improve outcomes.

Blood cancers can affect individuals of all ages and are characterized by many more genomic alterations than previously believed. This complexity necessitates a comprehensive genomic profiling approach. As evidenced by the promising efforts described above, we continue to make major advances in how we diagnose and treat these devastating diseases so as to bring the promise of precision medicine to more patients.

Visit our ASH 2018 page for all Foundation Medicine abstracts and posters, as well as those to which Foundation Medicine has contributed (subject to availability).

Learn more about The Leukemia & Lymphoma Society’s Beat AML trial here.



Notes

1 Severson et al. Genomic landscape of adult and pediatric BCR-ABL1-like B-lymphoblastic leukemia using parallel DNA and RNA sequencing. The Oncologist, 2018.