Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study.

Abstract

The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients] were assessed in this non-interventional study. Median age of the patients was 33.5 years (range 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype are correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, NA=6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). Mean of DeltaSUVmax after C2 was -78.8%. We analyzed ctDNA after C2 for 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.

• Authors: Vincent Camus, Mathieu Viennot, Justine Lequesne, Pierre-Julien Viailly, Elodie Bohers, Lucile Bessi, Bénédicte Marcq, Pascaline Etancelin, Sydney Dubois, Jean-Michel Picquenot, Elena-Liana Veresezan, Marie Cornic, Lucie Burel, Justine Loret, Stéphanie Becker, Pierre Decazes, Pascal Lenain, Stéphane Lepretre, Emilie Lemasle, Hélène Lanic, Anne-Lise Ménard, Nathalie Contentin, Hervé Tilly, Aspasia Stamatoullas, Fabrice Jardin
• Journal: Haematologica (Haematologica) Vol. 106 Issue 1 Pg. 154-162 (01 01 2021) ISSN: 1592-8721 [Electronic] Italy
• PMID: 32079702 (Publication Type: Clinical Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA
• Bleomycin
• Vinblastine
• Dacarbazine
• Doxorubicin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor
• Bleomycin (therapeutic use)
• Circulating Tumor DNA (genetics)
• Dacarbazine (therapeutic use)
• Doxorubicin (therapeutic use)
• Genotype
• Hodgkin Disease (diagnosis, drug therapy, genetics)
• Humans
• Middle Aged
• Mutation
• Prospective Studies
• Retrospective Studies
• Vinblastine (therapeutic use)
• Young Adult