San Diego, California—Dynamic changes in circulating tumor DNA (ctDNA) that occur very early during therapy may predict outcomes for patients with mantle cell lymphoma, according to a recent analysis.

These findings were presented by Rahul Lakhotia, MD, Lymphoid malignancies branch, Center for Cancer Research, National Cancer institute, National Institutes of Health, Bethesda, Maryland, at the 2018 ASH Annual Meeting.

“Circulating tumor DNA (ctDNA) is a highly tumor-specific biomarker detectable in the blood of virtually all MCL patients,” said Dr Lakhotia and colleagues, who analyzed the clinical significance of ctDNA dynamics during therapy in patients undergoing treatment with bortezomib and dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) without consolidation.

Patients received bevacizumab alone for 1 cycle then induction with bevacizumab plus DA-EPOCH-R up to 6 cycles. After induction, patients were randomized to observation or maintenance bevacizumab for 18 months.

Serum was prospectively collected prior to treatment, after bevacizumab monotherapy, before each cycle, after induction, and with each surveillance visit. Pre-treatment specimens were analyzed for tumor-specific clonotypes. Levels of ctDNA were analyzed at baseline, after bevacizumab monotherapy, and after cycles 1 and 2 of induction.

Between September 2005 and January 2016, a total of 53 untreated patients with MCL received bortezomib and DA-EPOCH-R. After a median potential follow-up of 10 years, the median progression-free survival (PFS) is 29.3 months and 5-year overall survival (OS) is 78.2%. Bevacizumab maintenance had no impact on PFS or OS.

Of 52 patients with available biopsies, 50 (96%) had a tumor-specific clonotype identified. Of 48 patients with pre-treatment serum, 46 (86%) had detectable ctDNA, which was successfully tracked in 625 of 647 serum samples. The median level of ctDNA at baseline was 742.98 cell equivalents/mL (range 0 to 101,008.58). Baseline ctDNA was correlated with total metabolic tumor volume on PET scan but was not associated with PFS or OS. Of 42 patients who received bevacizumab monotherapy, 26 (62%) had decreases in ctDNA, 15 (36%) had increases, and 1 (2%) had no change. The median absolute decrease in ctDNA was 35 cell equivalents/ml (range -20,901 to +6,667) and the median relative decrease was 24% (range -100% to +530%).

Lower absolute ctDNA levels after bevacizumab were associated with improved PFS compared with patients whose ctDNA levels were about the median (34 months vs 22 months, p=0.23). Clearance of ctDNA after 2 cycles of bevacizumab plus DA-EPOCH-R was also associated with a superior median PFS (32.4 months vs 21.4 months, p=0.015) and a trend towards superior median OS (82.2 months vs 73.2 months, p=0.15).

“Dynamic changes that occur very early during therapy may predict clinical outcomes and may be an early readout for the activity of targeted agents,” concluded Dr Lakhotia and colleagues.

“Given its broad applicability, ctDNA should be prospectively studied as part of response-adapted approaches in MCL,” they added.—Janelle Bradley

Lakhotia R,  Melani C, Pittaluga S, et al. Circulating Tumor DNA Dynamics during Therapy Predict Outcomes in Mantle Cell Lymphoma. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 147.