Pre-existing clonal hematopoiesis of indeterminate potential (CHIP) variants are associated with therapy-related myeloid neoplasms (t-MNs) in ovarian cancer patients treated with rucaparib, according to a study published in JAMA Oncology.

The prevalence of pre-existing CHIP variants in TP53, but not other CHIP-associated genes, was significantly higher in patients with t-MNs, researchers found.

The team retrospectively analyzed peripheral blood samples from 64 patients treated with rucaparib in the ARIEL2 trial (ClinicalTrials.gov Identifier: NCT01891344) and the ARIEL3 trial (ClinicalTrials.gov Identifier: NCT01968213).


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The group included 20 patients who developed t-MNs and 44 random patients who did not. Next-generation sequencing was used to identify CHIP variants.

At least 1 CHIP event occurred in 45.0% of patients with t-MNs and 25.0% of those without t-MNs (odds ratio [OR], 2.5; 95% CI, 0.8-7.9; P =.10).

There were no significant differences between patients with and without t-MNs in the prevalence of variants in DNMT3A, TET2, and ASXL1.

However, variants in TP53 were significantly more common in patients with t-MNs than without — 45.0% and 13.6%, respectively (OR, 5.2; 95% CI, 1.6-16.0; P =.009).

Patients with TP53 CHIP variants had significantly longer exposure to prior platinum therapies than patients without these variants — a mean of 14.0 months and 11.1 months, respectively (P =.02).

Similarly, patients with t-MNs had longer platinum exposure than patients without t-MNs in both ARIEL2 (a median of 13.2 months and 9.0 months, respectively; P =.04) and ARIEL3 (a median of 12.4 months and 9.6 months, respectively; P =.003).

“The findings of this genetic association study suggest that pre-existing TP53 CHIP variants may be associated with t-MNs after rucaparib treatment,” the researchers concluded.

Disclosures: This research was partly supported by Clovis Oncology. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Kwan TT, Oza AM, Tinker AV, et al. Preexisting TP53-variant clonal hematopoiesis and risk of secondary myeloid neoplasms in patients with high-grade ovarian cancer treated with rucaparib. JAMA Oncol. Published online October 14, 2021. doi:10.1001/jamaoncol.2021.4664