Real-world patient management practices in responders to venetoclax for newly diagnosed acute myeloid leukemia.

Venetoclax (VEN) is approved for adult patients (pts) with newly diagnosed (ND) acute myeloid leukemia (AML) in combination with hypomethylating agents (HMAs) or low dose cytarabine. This abstract describes real-world pt management practices among pts with ND AML who respond to VEN+HMA. The AML Real world evidenCe (ARC) Initiative is a multicenter chart review study of adults with ND AML treated with VEN at 17 academic sites in the US, Israel, and Canada. Pts ineligible for intensive chemotherapy (IC; ie, aged ≥75 years or ≥1 Ferrara criteria comorbidity) who initiated VEN+HMA on or after April 2016 were included (ie, before and after release of product label). Pt management practices in first-line VEN treatment and related impact on duration of response (DoR; assessed with Kaplan-Meier analyses) were examined among pts achieving composite complete remission (CRc; ie, CR or CR with partial hematologic recovery or incomplete count recovery). Among IC-ineligible VEN-treated pts, 116 (60.4%) achieved CRc (median age 73.0 years, 37.9% female, 53.4% European LeukemiaNet 2017 adverse risk, 24.2% Eastern Cooperative Oncology Group grade ≥2). Median DoR was 11.0 months (95% confidence interval: 8.8; 15.2). Most pts (75.9%) received VEN + azacitidine. Median observed VEN treatment duration was 5.8 months and 31.9% remained on VEN as of data entry; 12.1% received hematopoietic stem cell transplant post-VEN. Almost all pts (93.6%) had ≥1 marrow assessment post-VEN initiation, usually in cycle 1 (68.0%) or 2 (19.4%). During VEN treatment, 44.8% received granulocyte colony stimulating factor. Antifungals were used in cycle 1 by 68.1% (83.5% prophylactic; 63.3% strong CYP3A4 inhibitor); DoR did not differ by antifungal use. Most pts (68.1%) had VEN dose ramp-up, from a median of 100 mg to 400 mg daily over 3 days. In cycle 1, 59.5% started with 28 VEN dosing days; this proportion declined in subsequent cycles. Among pts still treated, 48.6% and 54.8% had ≤21 dosing days in cycles 2 and 3, respectively. Most pts achieved CRc in cycle 1 (58.6%) or 2 (21.6%); median DoR did not differ significantly between these pts vs later responders. Among 93 pts treated for ≥1 cycle post-response, most (87.1%) had a dose hold before initiating the next cycle; 51.6% of these 93 pts had a dose hold up to 14 days. Of 50 pts remaining on 28 dosing days until CRc, 26.0% reduced to ≤21 dosing days in the next cycle. Neither postremission dosing days modifications nor between-cycle dose holds significantly impacted DoR. Among VEN-treated ND pts with AML achieving CRc in real-world academic settings, most achieved CRc by the end of cycle 2, consistent with clinical trial results. Nevertheless, timing of response did not appear to affect DoR. Postremission dosing days modifications and between-cycle dose holds were common in clinical practice and did not appear to impact DoR.

Duke Scholars

Author Thomas William LeBlanc Medicine, Hematologic Malignancies and Cellular Therapy