Venetoclax monotherapy in elderly patients with secondary acute myeloid leukemia

The oral selective B cell lymphoma 2 (BCL2) inhibitor, venetoclax, has previously demonstrated promising clinical responses as a monotherapy in patients with high-risk relapsed/refractory (R/R) acute myeloid leukemia (AML).¹ In addition to this, venetoclax has shown clinical efficacy in combination with low-dose cytarabine or hypomethylating agent (HMA) therapy in elderly patients with previously untreated AML, who are unfit for intensive chemotherapy.^2,3

Dr. Florian Huemer and Dr. Thomas Melchardt, from the Paracelsus Medical Private University, Salzburg, Austria, and colleagues published a retrospective case series analysis in the European Journal of Haematology. This study reported on the clinical outcomes and biomarker correlates of elderly patients (n = 7; median age = 74 years; range, 65–82) with secondary R/R AML who were considered unfit for intensive induction chemotherapy. Patients received venetoclax monotherapy at a single center, with an increasing dosing schedule (target dose = 800 mg/day), following treatment failure with HMAs.⁴

Key findings:

• At data cut-off, 19 October 2018, all patients (n = 7) had discontinued venetoclax monotherapy, and 6 patients had died
• Median progression-free survival (PFS) on prior HMA therapy: 222 days (range, 12–325)
• Median overall survival (OS) from initiation of venetoclax monotherapy: 55 days (range, 15–549)
• Two patients achieved complete remission: PFS of 505 and 352 days, respectively
  • Antileukemic benefit was seen in a third patient with complete peripheral blood blast clearance by day 9
  • The four non-responders showed rapid disease progression ≤35 days following venetoclax initiation
• Patients with high BCL2 and/or BIM expression were more likely to respond to venetoclax monotherapy, with response associated with superior median OS: 364 days (responders) vs 24 days (non-responders), P = 0.018
• Median OS from venetoclax initiation was greater in patients with primary refractory disease following HMA therapy, compared to HMA-responders: 126 days vs 15 days, P = 0.018

In conclusion, this retrospective analysis illustrated that venetoclax monotherapy is effective in elderly patients with secondary AML following failure to HMA therapy. This study highlighted that high baseline levels of BCL2 and/or BIM may help to identify patients who will respond to a regimen of venetoclax therapy. Due to the retrospective nature of this analysis, further prospective clinical trials are needed to validate these findings.