Treatment and Response
All patients received venetoclax in combination with either a hypomethylating agent or conventional chemotherapy. Median follow-up time was 8 months from venetoclax initiation (range 2 to 52 months). Treatment regimens and responses for each patient are summarized inTable 2 and in Figure 1. The standard adult AML dosing of 400 mg daily (or adult equivalent weight-based dosing), with a bioequivalent dose for patients receiving a concurrent CYP3A4 inhibitor, was given.17,18 Three of 8 patients with AML received venetoclax in combination with decitabine (20 mg/m2daily for 5 days). In two of these three cases, the patient was a poor candidate for conventional chemotherapy due to morbidities from prior therapy; in one case, the patient with SDS and newly-diagnosed AML was deemed ineligible for standard chemotherapy due to the risk of toxicity.19 The remaining 5 patients with AML received venetoclax in combination with cytarabine (1000 mg/m2/dose every 12 hours for 8 total doses). One patient with an intracranial myeloid sarcoma received venetoclax and cytarabine with concomitant focal radiation therapy. Both patients with MDS received venetoclax in combination with a hypomethylating agent (decitabine in one case and azacitidine in the other).
Two of the three patients with relapsed B-ALL received venetoclax in combination with vincristine, dexamethasone, and PEG-asparaginase. One patient with relapsed B-ALL received venetoclax in combination with fludarabine, high-dose cytarabine, and G-CSF (FLAG).
The median number of cycles of venetoclax combination therapy patients received was 1 (range <1 to 3). The most common reason for discontinuation of venetoclax was disease progression in 6 patients (46%), and in 2 cases it was discontinued due to infections.
Three (23%) patients achieved a CR; 2 (15%) achieved a PR; 3 (23%) had stable disease, and 5 (42%) had PD. Of the 3 patients who achieved a CR, two had a diagnosis of relapsed B-ALL, and one had a diagnosis of SDS-associated AML. Two of these patients became MRD negative after one cycle of venetoclax combination therapy. All three patients who achieved a CR remain alive with no evidence of disease with a median follow-up time of 48 months.
Nine patients (69%) experienced disease progression following venetoclax therapy. Median survival was 9 months from venetoclax initiation (range 2.5 to 52 months), and median time to progression was 3 months (range 2 weeks to 7.5 months). (Fig. 2).