The following article features coverage from the European Society of Medical Oncology (ESMO) Congress 2021. Click here to read more of Hematology Advisor’s conference coverage.

Among patients with chronic myelomonocytic leukemia (CMML) or other myelodysplastic/myeloproliferative neoplasms (MDS/MPN), tipifarnib appears to show some clinical activity, according to research presented at the European Society for Medical Oncology Congress 2021.

Patients with CMML who have RAS pathway mutations, which occur in approximately 30% of cases, have a higher risk of adverse outcomes. Tipifarnib — a selective inhibitor of farnesyl-transferase — may, according to previous research, be effective among patients with wild-type RAS.

There is, however, evidence that RAS isoforms are substrates of farnesyl-transferase. For this single-arm, phase 2 study ( Identifier: NCT02807272), researchers evaluated the safety and efficacy of tipifarnib in a population of patients with CMML or MDS/MPN who had biomarkers of interest.

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All patients received oral tipifarnib 400 mg on days 1 to 21 of 28-day cycles until disease progression or discontinuation due to toxicity. The study’s dual primary objectives were objective response rate (ORR) in patients with KRAS/NRAS wild-type vs mutant CMML and ORR among patients with MDS/MPN with a high vs low bone marrow CXCR4/CXCR2 ratio.

Overall, 44 patients were enrolled and received tipifarnib; 37 patients had CMML and 7 had MDS/MPN. Among patients with CML, 32 were evaluable for ORR, which was determined to be 21.9%. In 30 patients with known KRAS/NRAS status, 3 of 21 (14.3%) with wild-type KRAS/NRAS vs 3 of 9 (33.3%) with mutated KRAS/NRAS had an objective response.

Only 4 patients with MDS/MPN were, however, evaluable for ORR, rendering subgroup analysis impossible. Among these patients, 1 objective response was recorded.

Fifteen patients (34%) had a serious treatment-related adverse event; 7 (16%) discontinued treatment because of a treatment-related event. No treatment-related deaths were noted.

“Overall, data from this [phase 2] trial showed that in general, tipifarnib was reasonably well tolerated and demonstrated modest efficacy in a difficult-to-treat patient population with limited therapeutic options,” the authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Read more of Hematology Advisor’s coverage of ESMO 2021 by visiting the conference page.


Patnaik MM, Sekeres MA, DeZern A, et al. Final results of a phase II study of tipifarnib in chronic myelomonocytic leukemia (CMML) and other myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Presented at: European Society for Medical Oncology 2021 Congress; September 16-21, 2021. Abstract 854P.