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).