A phase I clinical trial to study the safety of treatment with tipifarnib combined with bortezomib in patients with advanced stages of myelodysplastic syndrome and oligoblastic acute myeloid leukemia. (June 2021)

• Record Type: Journal Article
• Authors: Muus, Petra; Langemeijer, Saskia; van Bijnen, Sandra; Blijlevens, Nicole; de Witte, Theo
• Is Part Of: Leukemia research. Volume 105(2021)
• Publication Date: 2021-06
• Subjects: Farnesyltransferase inhibitor -- Tipifarnib -- Proteasome inhibitor -- Bortezomib -- Phase I -- Hypomethylating agents -- Myelodysplastic syndromes -- Acute myeloid leukemia; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2021.106573
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: First ever report on safety and effectivity of tipifarnib and in combination with and bortezomib in adults with treatment naïve higher risk MDS and AML with less than 30 % blasts. The regimen was tolerated well and generated clinical responses. Literature with either of the two agents in MDS / AMLor both (only one study in heavily pretreated AML) are reviewed. A possible place for the combination in the current MDS/AML treatment schema is discussed. Patients who failed vidaza or decitabine may profit from this treatment. Abstract: Purpose: To determine the safety of tipifarnib in combination with escalating doses of bortezomib and to determine the maximum tolerated dose in patients with untreated high-risk MDS and oligoblastic acute myeloid leukemia, who were not eligible for intensive therapy. Experimental Design: In a "3 + 3″ design, patients received fixed doses of tipifarnib 200 mg bid (days 1–21) and escalating doses of bortezomib (days 8, 15, 22) every 4 weeks in 4–6 cycles. Results: The combination was tolerated well by the 11 patients in this study without reaching the maximum tolerated dose. Myelosuppression was the most frequent side effect, but usually of short duration. Interestingly a complete response with or without complete count recovery was observed in three patients and three additional patients had stable disease. The median duration of overall survival was 449 days. Two patients were still alive at 4.0 and 4.3 years, including one patient in continuing CR. Conclusions: The combination of tipifarnib and bortezomib was tolerated well and appeared to have clinical activity in patients with high-risk MDS and AML with low counts of marrow blasts. Our results warrant further evaluation in a phase II study.