Subclonal TP53 mutations are frequent and predict resistance to radioimmunotherapy in follicular lymphoma

W. Richard Burack, Hongli Li, Diana Adlowitz, Janice M. Spence, Lisa M. Rimsza, Mazyar Shadman, Catherine M. Spier, Mark S. Kaminski, John P. Leonard, Michael L. Leblanc, Sonali M. Smith, Jonathan W. Friedberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Although TP53 is commonly mutated in transformed follicular lymphoma, mutations are reported in <5% of pretreatment follicular lymphoma (FL) specimens. We assayed archival follicular B-cell non-Hodgkin lymphoma specimens from a completed clinical trial, Southwest Oncology Group S0016, a phase 3 randomized intergroup trial of CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) chemotherapy plus R-CHOP (rituximab-CHOP) compared with CHOP chemotherapy plus 131-iodine tositumomab (radioimmunotherapy [RIT]-CHOP). Subclonal TP53 mutations (median allele frequency 0.02) were found in 25% of diagnostic FL specimens and in 27% of a separate validation cohort. In the R-CHOP arm, pathogenic TP53 mutations were not associated with progression-free survival (PFS) (10-year PFS 43% vs 44%). In contrast, among patients with no detectable pathogenic TP53 mutation, RIT-CHOP was associated with a longer PFS than with R-CHOP (10-year PFS 67% vs 44%; hazard ratio = 0.49; P = .008). No relationship was detected between PFS and the extent of activation-induced cytidine deaminase (AICDA)-mediated heterogeneity. In summary, subclonal TP53 mutations are common in FL and are a distinct phenomenon from AICDA-mediated genetic heterogeneity. The absence of a detectable subclonal mutation in TP53 defined a population that particularly benefited from RIT.

Original languageEnglish (US)
Pages (from-to)5082-5090
Number of pages9
JournalBlood Advances
Volume7
Issue number17
DOIs
StatePublished - Sep 12 2023
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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