Precision Medicine Approach Leads to ‘Exceptional Responses’ in Patients With Aggressive Hematologic Cancers

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A precision medicine approach proved clinically feasible and effective for patients with advanced hematologic cancers, according to researchers. The team described the approach in Cancer Discovery.

In the EXALT trial (ClinicalTrials.gov Identifier: NCT03096821), researchers used an image-based single-cell functional precision medicine (scFPM) approach to guide treatment of patients with aggressive hematologic cancers.

The researchers obtained cancer cells from patients via biopsy, bone marrow aspirate, or peripheral blood draw. The team then tested potential treatments on the cells ex vivo and used the results to guide treatment decisions for the patients.


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Of the 143 eligible patients, 56 were treated based on the results of scFPM. The patients had acute myeloid leukemia (n=14), B-cell non-Hodgkin lymphoma (n=26), or T-cell non-Hodgkin lymphoma (n=16). The patients’ median age was 64 years (range, 23-86 years), and they had received a median of 3 (range, 1-8) prior therapies.

At a median follow-up of 23.9 months, 30 patients reached a progression-free survival (PFS) ratio of 1.3 or higher, with a median PFS ratio of 3.4 (interquartile range, 2.2-5.7).

“This indicates that their individual PFS on scFPM-guided treatment more than tripled when compared to their most recent individualized response time,” the researchers explained.

Overall, there was a significant increase in PFS with scFPM-guided treatment compared with patients’ prior treatment (hazard ratio, 0.58; P =.0093). The 1-year PFS rate was 23% with scFPM-guided therapy and 5% with previous treatment.

The objective response rate was 55% for all patients who received scFPM-guided therapy — 60% for patients with lymphoid malignancies and 41% for patients with myeloid neoplasms.

The researchers identified 12 patients (40% of responders) who were “exceptional responders.” These patients had a 3-fold longer PFS than would be expected for their disease.

Patients treated based on scFPM also had a significant overall survival benefit compared with the observational cohort (P =.035). The observational cohort encompassed 20 patients who were not treated based on scFPM and instead received physician’s choice of treatment.

“The results of the EXALT study … show that scFPM can be an effective tool for clinical decision-making and therapy optimization based on the functional characteristics of each patient’s tumor,” the researchers concluded. “The EXALT trial shows that functional testing can be integrated into clinical workflows and provide individual patient benefit for late-stage hematological cancer patients.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Kornauth C, Pemovska T, Vladimer GI, et al. Functional precision medicine provides clinical benefit in advanced aggressive hematological cancers and identifies exceptional responders. Cancer Discov. Published online October 11, 2021. doi:10.1158/2159-8290.CD-21-0538



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