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15-ICML: Genotyping of ctDNA in Classical Hodgkin Lymphoma

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Key Points

  • Variants were identified in 55% of patients, precisely in 53.3% of available biopsy samples and in 50% of available ctDNA samples.
  • Mutations in NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13, and SOCS1 were found.
  • Higher level of ctDNA at diagnosis was associated with age ≥ 45 years, presence of anemia, albuminemia < 40 g/L, sedimentation rate ≥ 50 mm, stage III to IV disease, lymphocyte count < 0.6 g/L, presence of B symptoms, International Prognostic Index ≥ 3, and elevated lactate dehydrogenase. Patients with mutations in ITPKB and B2M had more disseminated disease then patients with no mutations.
  • Median variant allele fraction was higher in ctDNA than in biopsy, and there was a moderate correlation between higher metabolic tumor volume and higher ctDNA.

An abstract presented by Camus et al at the 15th International Conference on Malignant Lymphoma (ICML; Abstract 138) found that targeted genotyping of circulating tumor DNA (ctDNA) in classical Hodgkin lymphoma at diagnosis “may help to assess early treatment response in complement to positron-emission tomography.”

Methods

Researchers developed a targeted next-generation sequencing panel to analyze nine commonly mutated genes in patients with classical Hodgkin lymphoma, either through biopsy or ctDNA samples. They then assessed ctDNA follow-up at diagnosis and after two cycles of chemotherapy. Sixty patients treated with first-line chemotherapy (BEACOPP escalated [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone], 21.3%) ABVD/ABVD-like (doxorubicin, bleomycin, vinblastine, and dacarbazine, 73.5%), and other regimens (5.2%) were included in this prospective trial.

Findings

Variants were identified in 55% of patients, precisely in 53.3% of available biopsy samples and in 50% of available ctDNA samples. Concordance between the genetic profiles for biopsy and ctDNA samples was accurate for 73.3% of patients.

Mutations in NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13, and SOCS1 were found.

Higher level of ctDNA at diagnosis was associated with age ≥ 45 years, presence of anemia, albuminemia < 40 g/L, sedimentation rate ≥ 50 mm, stage III to IV disease, lymphocyte count < 0.6 g/L, presence of B symptoms, International Prognostic Index ≥ 3, and elevated lactate dehydrogenase. Patients with mutations in ITPKB and B2M had more disseminated disease then patients with no mutations. Patients with mutations in XPO1 were more likely to be female. Median variant allele fraction was higher in ctDNA than in biopsy (3.23% vs 21.5%, P = .023), and there was a moderate correlation between higher metabolic tumor volume and higher ctDNA.

Regarding early therapeutic response, 83% of patients had a negative positron emission tomography after two cycles of chemotherapy. Researchers analyzed ctDNA after the two cycles of chemotherapy in 70% of patients, and rapid clearance of ctDNA in all cases was observed.

The researchers concluded, “ctDNA level and genotype are correlated with clinical characteristics and presentation.”

Disclosure: For full disclosures of the study authors, visit lymphcon.ch.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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