GLASDEGIB WITH LDAC IN NEWLY DIAGNOSED PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) UNSUITABLE FOR INTENSIVE CHEMOTHERAPY: EFFECTS ON TRANSFUSIONS AND MARROW RECOVERY VS LDAC ALONE
Author(s): ,
Eunice S Wang
Affiliations:
Roswell Park Comprehensive Cancer Center,Buffalo, NY,United States
,
Michael Heuser
Affiliations:
Hannover Medical School,Hannover,Germany
,
Pau Montesinos
Affiliations:
Hospital Universitari i Politècnic La Fe,Valencia,Spain;CIBERONC, Instituto Carlos III,Madrid,Spain
,
Mikkael A Sekeres
Affiliations:
Cleveland Clinic,Cleveland, OH,United States
,
Akil Merchant
Affiliations:
Cedars-Sinai Medical Center,Los Angeles, CA,United States
,
Carmen Pedro Olive
Affiliations:
Hospital del Mar,Barcelona,Spain
,
Olga Salamero
Affiliations:
Valle d' Hebrón Hospital,Barcelona,Spain
,
James K McCloskey
Affiliations:
John Theurer Cancer Center,Hackensack, NJ,United States
,
Caroline J Hoang
Affiliations:
Pfizer Inc,New York, NY,United States
,
Wei Dong Ma
Affiliations:
Pfizer Inc,New York, NY,United States
,
Mirjana Zeremski
Affiliations:
Pfizer Inc,New York, NY,United States
,
Ashleigh O’Connell
Affiliations:
Pfizer Inc,New York, NY,United States
,
Geoffrey Chan
Affiliations:
Pfizer Inc,New York, NY,United States
Jorge E Cortes
Affiliations:
University of Texas, MD Anderson Cancer Center,Houston, TX,United States
EHA Library. S Wang E. Jun 14, 2019; 266072; PF272
Dr. Eunice S Wang
Dr. Eunice S Wang
Contributions
Abstract

Abstract: PF272

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
The United States FDA recently approved glasdegib (GLAS) in combination with low-dose cytarabine (LDAC) for AML in patients not suitable for intensive chemotherapy. Approval was based on a Phase 2 randomized trial showing overall survival benefit vs LDAC alone. No increased risk of infectious or bleeding complications was seen, with lower rates of hemorrhage (36% vs 42%) and pneumonia (19% vs 24%) with GLAS+LDAC vs LDAC alone. This is consistent with the mechanism of GLAS, which inhibits the hedgehog pathway (not implicated in normal hematopoiesis).

Aims
To evaluate hematopoietic recovery and transfusion independence with GLAS+LDAC vs LDAC alone.

Methods
This post hoc analysis included AML patients receiving GLAS 100 mg QD + LDAC (n=75) or LDAC alone (n=36) in the Phase 2 randomized trial (NCT01546038). We compared transfusion rates and recovery of 3 cell lineages, all at 2 thresholds: absolute neutrophil count (ANC; ≥1000 or 500/µL), hemoglobin (Hb; ≥10 or 9 g/dL), and platelets (≥100,000 or 50,000/µL); requiring measurements at ≥2 consecutive visits. Time to recovery and cycle analyses required ≥1 on-study measurement; cycle analysis included only remaining patients at risk in that cycle. Patients receiving transfusions were not excluded from analyses.

Results
The median treatment duration was 3 cycles (range 1–44) for the GLAS+LDAC arm and 2 (range 1–9) for the LDAC-alone arm. For all 3 cell lineages, a higher proportion of patients had measurements above the thresholds at ≥2 consecutive visits with GLAS+LDAC, with greater differences for patients below threshold at baseline (Table). For ANC recovery, ≥1000/µL was achieved by 56% vs 38% of the GLAS+LDAC vs LDAC-alone arms, and ≥500/µL by 65% vs 53%. For Hb, ≥10 g/dL was achieved by 32% vs 22%, and ≥9 g/dL by 61% vs 41%. For platelets, ≥100,000/µL was achieved by 42% vs 13%, and ≥50,000/µL by 53% vs 25%. Compared with LDAC-alone, median time to recovery with GLAS+LDAC was longer for ANC, shorter for Hb, and similar for platelets (Table). For all 3 lineages, the proportion of patients achieving recovery in the GLAS+LDAC arm rose over cycles 2–3 and remained high (proportions to Cycle 44 generally: ANC ≥1000 >70%; ≥500 >80%; Hb ≥10 >50%; ≥9 >70%; platelets ≥100,000 >70%; ≥50,000 >80%). Patients in the GLAS+LDAC arm had fewer transfusions, regardless of study drug exposure (Table).

Conclusion
Blood count recovery for ANC ≥1000/µL, Hb ≥10 g/dL, and platelets ≥100,000/µL with GLAS+LDAC was seen as early as Cycle 1 for a meaningful proportion of patients, and counts were maintained or continued to improve during subsequent cycles in the remaining patients at risk. ANC recovery, at both 500 and 1000/µL thresholds, occurred in most patients during Cycle 2. Count recovery was consistent in all 3 lineages, and at different thresholds, regardless of baseline counts. The frequency of count recovery for GLAS+LDAC is higher than the 24% CR/CRi rate reported in this study, consistent with observed clinical benefit even in those not achieving complete remission. More GLAS+LDAC patients were transfusion-independent and when exposure-adjusted, LDAC-alone patients required transfusions twice as often; although quality of life was not measured, it is reasonable to expect improved quality of life and resource utilization with decreased transfusion requirements. The GLAS+LDAC combination is a promising option to minimize cytopenias in the upfront treatment of AML patients not suitable for intensive chemotherapy.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, Clinical trial, Neutropenia, Treatment

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