Background: Detection and longitudinal monitoring of the cell-free circulating tumor-specific DNA (ctDNA) in plasma of cancer patients is a potent tool for treatment response assessment and detection of the early disease recurrence. There is a number of the next-generation sequencing (NGS) panels for analysis of the commonly mutated genes in tumors of classic Hodgkin lymphoma (cHL) patients, which are being validated for clinical use. The Cleveland Clinic team, in collaboration with Adaptive Biotechnologies, is exploring if longitudinal assessment of ctDNA encoding the patient- and tumor cell-specific rearranged heavy or light (kappa/lambda) chain IgG (r-IgH/r-IgK/L, could be used for the treatment response and early recurrence monitoring in cHL patients.
Methods: Enrolled are patients (9-99 y) with newly diagnosed and previously untreated cHL. First, the diagnostic biopsy specimen and the pre-treatment plasma are tested for concordant presence of dominant r-IgH/r- IgK/L ctDNA sequences. Sequence dominance and suitability for tracking is determined according to the Adaptive Biotechnologies’ diagnostic algorithm validated for other B cell neoplasms. If dominant r-IgH/r-IgK/L sequence(s) is detected, the patient plasma is serially tested during and following completion of therapy.
Results: Pilot results on first 4 patients are presented. Patients’ clinical characteristics are summarized in Table 1. P1 had a single dominant r-IgH ctDNA sequence; P2 had two dominant r-IgH ctDNA sequences; P3 had two r-IgH and one dominant IgK ctDNA sequences; the latter was chosen for serial tracking; P4 had a single dominant r-IgH ctDNA sequence. In P1 and P2, the concentration of ctDNA precipitously declined below detectable threshold following completion of the first two cycles of therapy, and remained undetectable through the end of treatment. These laboratory changes correlated well with the treatment response assessed by functional imaging. For P2 and P3, the in-treatment samples are in process of acquisition.
Conclusion: The preliminary results of this pilot project demonstrate feasibility of establishing trackable ctDNA sequences encoding IgG heavy or light chain, with intra- and interpatient clonotypic heterogeneity of the dominant sequences. Correlation between results of the functional imaging treatment assessment and detectable quantity of ctDNA in plasma was observed. Further testing is underway.
Ilia Buhtoiarov, Brian Hill, Ilan Kirsch, Nancy Richter, Rabi Hanna