A small number of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) may benefit from chemotherapy intensification after not responding to venetoclax-based salvage therapy, according to a study published in the European Journal of Haematology

Remission and survival rates for patients with R/R AML who are unresponsive to first-line venetoclax therapies are poor; however, some of these patients may respond to chemotherapy intensification with venetoclax.

The authors performed a retrospective analysis of 28 patients who received multiple treatment lines and relapsed or did not achieve response after venetoclax-based salvage therapy. All patients received intensive chemotherapy with a median of 3 treatment lines; 16 patients received 1 or 2 allogeneic stem cell transplantations (alloSCT). Of the 16 receiving alloSCT, 13 relapsed within 1 year.

After initial venetoclax-based chemotherapy treatment, 22 patients received varying salvage treatments; 6 patients did not receive salvage treatment because of poor condition.


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The overall rate of complete remission (CR) was 18% (4 of 22 patients) and the overall response rate (ORR) was 23% (5 of 22 patients). Patients who received venetoclax-based salvage regimens before relapse had a response rate of 25%. Refractory patients had a CR rate of 10%.

Patients who received venetoclax with either actinomycin D or actinomycin D and low-dose cytarabine had a CR of 50% and a median overall survival of 9.4 months. Refractory patients had a CR of 10%. The authors suggest that cautiously intensifying chemotherapy with venetoclax in some patients may improve response.

Genetic mutations may contribute to lack of response to venetoclax-based therapies. In the analysis, 17 patients had adverse or complex karyotypes. However, targeted therapies did not induce object responses in the patient population analyzed.

The study only looked at data from patients treated at Vilnius University Hospital Santaros Klinikos, in Lithuania, and was limited by the small group size. Patients had similar characteristics and heterogeneity in their treatment regimens, limiting conclusions from the study.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Zucenka A, Pileckyte R, Trociukas I, et al. Outcomes of relapsed or refractory acute myeloid leukemia patients failing venetoclax based salvage therapies. Eur J Haematol. Published online September 30, 2020. doi:10.1111/ejh.13527