Pharmacosmos Therapeutics supplied trilaciclib and blood samples for use in the study
Pharmacosmos Therapeutics presented new investigator-sponsored research at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. The abstract, “CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis” (Abstract #8419), was featured during a Plenary Scientific Session on December 7.
Led by investigators from Washington University in St. Louis and Memorial Sloan Kettering Cancer Centre, the study examined whether the intravenous CDK4/6 inhibitor trilaciclib can reduce the expansion of chemotherapy-associated TP53-mutant clonal hematopoiesis (CH), which is a risk factor for therapy-related myeloid neoplasms (tMN).
Pharmacosmos Therapeutics provided trilaciclib and blood samples from clinical trials with trilaciclib for use in this study, but did not sponsor or conduct the research.
The research revealed that across three placebo-controlled trials involving patients with small cell lung cancer (SCLC, metastatic triple-negative breast cancer (mTNBC), and metastatic colorectal cancer (mCRC), administration of trilaciclib before chemotherapy was associated with a significantly lower rate of TP-53-mutant CH clone expansion compared to placebo.
Concomitant treatment with trilaciclib and carboplatin prevented the expansion of p53-mutant hematopoietic stem cells while preserving normal progenitor cells under cytotoxic stress in preclinical murine models.
Kelly Bolton, principal investigator and senior author, from Washington University in St. Louis, said, “The first time that an approach has been identified to reducing expansion of TP53-mutant CH during therapy. The data generated regarding trilaciclib’s role are emerging across multiple clinical contexts, consistently demonstrating a potential pattern of reduced TP53-mutant CH growth.”
Omar Abdel-Wahab, co-corresponding author from Memorial Sloan Kettering Cancer Centre, said, “Therapy related myeloid neoplasms are a very troubling complication of cancer therapy. There are currently very limited effective treatments when therapy-related myeloid neoplasms occur. We are very excited about this study, as the results provide the first clue about a strategy to prevent the development of therapy-related myeloid neoplasms.”
