Washington University School of Medicine, St. Louis, MO
Nicole C. Foley , David Russler-Germain , Marcus Watkins , Eric D. Jacobsen , Alison J. Moskowitz , Amanda F. Cashen , Todd A. Fehniger , Brad S. Kahl , Armin Ghobadi , Beth Reagan , Anne Fischer , Fei Wan , Austin Jacobsen , Karina Elias , Matt Holman , Natalie Hill , Skyler Gordon , Ying Huang , Steven M. Horwitz , Neha Mehta-Shah
Background: Roughly 80% of pts with peripheral T-cell lymphomas (PTCL) respond to CHOP-based therapy but 5-yr survival ranges between 20-40%. The high relapse rate after complete response (CR) suggests more sensitive response assessment, such as minimal residual disease (MRD) testing, could have prognostic or predictive value. Next generation sequencing (NGS) of the T-cell receptor (TCR) can detect a known TCR clonotype at 10-5. In a prospective study, we evaluated the utility of MRD testing via TCR NGS in PTCL (NCT03297697). Here we report results for pts pre- and post-autologous stem cell transplant (ASCT). Methods: This investigator-initiated, multi-institutional, prospective cohort study assessed MRD testing by TCR NGS in PTCL. Pts with previously untreated PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), PTCL with T-follicular helper (TFH) phenotype, or monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) treated with anthracycline-based curative-intent therapy were eligible. Baseline TCR (TRG or TRB) clonotypes were established from diagnostic tissue or peripheral blood if tissue was not available. TCR clonality was determined positive via the LymphoTrack TRG/TRB Assays – MiSeq (Invivoscribe, San Diego, CA) when top % reads were ≥2.5% and ≥2x above background. Samples were obtained at diagnosis (pre-treatment), following induction therapy (EOT/pre-ASCT), and serially post-ASCT. Results: Of 43 enrolled pts, 19 underwent consolidative ASCT, of which 10 had post-ASCT samples available for MRD testing (Table). Median age at ASCT was 62 years (range: 38-77). Baseline TCR clonotypes were identified in 10/10 pts. At pre-ASCT evaluation, 7/10 pts had detectable TCR MRD (‘pos’) and 3/10 pts had TCR MRD below the level of detection (‘neg‘). Of the 3 MRD neg pts pre-ASCT, 2 had CR and 1 had PR by PET-CT. All 7 TCR MRD pos pts pre-ASCT had CR by PET-CT. Of 7 MRD pos pts pre-ASCT, 6 remained MRD pos and 1 became MRD neg post-ASCT. Of the 4 MRD neg pts post-ASCT, none have relapsed at 52, 31, 34, and 31 mo post-ASCT. Of 7 MRD pos pts pre-ASCT, 3 have relapsed following ASCT (at 3, 9, and 29 mo post-ASCT). Conclusions: In this cohort of patients with PTCL receiving consolidative ASCT in CR1, all 4 pts with negative TCR MRD post-ASCT remain in remission at median follow up of 32.5 mo post-ASCT. The negative predictive value of TCR NGS MRD post-ASCT should be further evaluated. Clinical trial information: NCT03297697.
Pt # | Age | Dx | Induction | Pre-ASCT MRD | Pre-ASCT PET/CT | Post-ASCT MRD | Relapse post-ASCT | Follow-up Post-ASCT (mo) |
---|---|---|---|---|---|---|---|---|
1 | 52 | ALK- ALCL | CHOEP | - | PR | - | No | 52 |
2 | 39 | AITL | BV+CHP | - | CR | - | No | 31 |
3 | 69 | PTCL NOS | BV+CHP | - | CR | - | No | 34 |
4 | 71 | AITL | Aza + CHOP | + | CR | - | No | 31 |
5 | 68 | AITL | CHOEP | + | CR | + | No | 51 |
6 | 77 | AITL | Aza + CHOP | + | CR | + | Yes (3 mo) | 10 (died) |
7 | 70 | MEITL | CHOEP | + | CR | + | Yes (9 mo) | 11 (died) |
8 | 68 | PTCL NOS | CHOP | + | CR | + | No | 20 |
9 | 38 | AITL | Aza + CHOP | + | CR | + | No | 28 |
10 | 67 | TFH PTCL | Aza + CHOP | + | CR | + | Yes (29 mo) | 29 |
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