P1182: a prospective study of tcr measurable residual disease in peripheral t-cell lymphoma

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Peripheral T-Cell Lymphoma (PTCL) is an aggressive rare subset (~10-15%) of non-Hodgkin lymphomas. PTCL treatment often starts with anthracycline based chemotherapy and then autologous stem cell transplantation (ASCT) for applicable patients. PET/CT has been used to monitor disease recurrence after the end of chemo treatment. However, its ability to predict relapse for PTCL is not ideal. In this prospective study, we explored the use a next-generation-sequencing (NGS) based TCR measurable residual disease (MRD) assay as a potential prognostic indicator for PTCL (NCT03297697). Aims: To explore TCR MRD assays as a potential prognostic biomarker in a prospective study of PTCL patients. Methods: 43 eligible patients with previous untreated PTCL (PTCL-NOS, AITL, ALK-ALCL, ALK+ALCL, PTCL-NOS-TFH, and MEITL) were enrolled in this study. LymphoTrack® TCR (TRG/TRB) assays, which demonstrates 10-5 sensitivity, were used to test both baseline samples (either tissue or PB), PB samples from end of chemo treatment (EOT/pre-ASCT), stem cells from eligible ASCT patients, and PB samples from post -ASCT patients. The stem cells were collected according to institutional protocols by apheresis after granulocyte colony stimulating factor (G-CSF) to stimulate the bone marrow production of stem cells for extraction. Clonality from baseline and stem cell samples was determined when the top % reads from this assay are ≥2.5% and ≥2x the background. The identified clonal sequences from the baseline samples were then tracked for MRD assessment in both EOT and post-ASCT samples from the same patients. Results: Of 43 enrolled patients, 41 provided baseline samples. 32 out of 41 baseline samples had detectable TCR clonal sequences for MRD tracking. Of the 32 patients, 30 had EOT samples available. 80% (24/30) patients had TCR MRD positive and 20% had MRD negative. Within the MRD positive group, 63% (15/24) patients had CR and 37% (9/24) had PR/PD at EOT. Within the MRD negative group, 4 patients had CR and 2 had PR at EOT. A total of 19 patients underwent consolidative ASCT after chemo, of which 10 patients had samples available for post-ASCT MRD testing. All 10 patients had detectable clonal sequence in baseline samples. Of the 10 ASCT patients, 7 provided stem cells for clonality analysis. 3 out of the 7 stem samples were TCR clonal. However, none of the clonal sequences matched with the sequences in the corresponding baseline samples. MRD analysis of the 10 ASCT patients shows 3 patients status remained TCR MRD negative from pre-ASCT to post ASCT and no relapse at 52, 31 and 34 months post-ASCT. 1 patient changed MRD status from MRD positive at pre-ASCT to MRD negative at post-ASCT and no relapse at 31 months post-ASCT. 6 patients remained TCR MRD positive status from pre-ASCT to post ASCT, 3 had relapsed at 3, 9 and 29 months post-ASCT, 3 had no relapse at 51, 20 and 28 months post-ASCT. Summary/Conclusion: We have demonstrated that NGS-based LymphoTrack® TCR assays are able to identify clonality from baseline and stem cell samples, and detect MRD in post-treatment (EOT and post ASCT) samples from PTCL patients in a prospective study. Clonality analysis of stem cells confirmed absence of the matched baseline clonal sequences. All 4 patients who tested MRD negative post-ASCT remain in remission at median 32.5 months after ASCT treatment. The negative predictive value of TCR MRD negative in post-ASCT should be further evaluated with a larger sample size. Keywords: Peripheral T-cell lymphoma, Minimal residual disease (MRD), Non-Hodgkin’s lymphoma, Clonality