Clinical Outcomes of Patients with AML Receiving Lower Intensity Chemotherapy with or without the Use of Granulocyte-Colony Stimulating Factor (GCSF)

Introduction: Lower intensity chemotherapy combined with the BCL2 inhibitor venetoclax (VEN) is the standard for newly diagnosed AML among patients (pts) aged ≥ 75 years (yrs) or those ineligible for intensive therapy. Despite being classified as ‘lower-intensity’, these regimens are associated with frequent, often prolonged cytopenias, and infectious complications in the setting of neutropenia can add to the burden of morbidity and mortality. Granulocyte-colony stimulating factor (GCSF) is often integrated into intensive therapy in AML and used ad hoc among pts treated with VEN-based low intensity therapy. There is a lack of data which assesses the safety, clinical utility, and outcomes with GCSF in this setting. We evaluated count recovery, incidence of infection/febrile neutropenia (FN), overall survival (OS), and relapse-free survival (RFS) in pts with newly diagnosed AML treated with lower intensity therapy with or without GCSF.

Methods: This retrospective study included pts with newly diagnosed AML treated with VEN in combination with a hypomethylating agent (HMA) (intravenous [IV] azacitidine, IV decitabine, or oral decitabine/cedazuridine [ASTX]) or with cladribine + low-dose cytarabine (CLAD/LDAC). Response rates, early mortality, OS, RFS, incidence of infection/FN, and time to blood count recovery in induction (C1) and C2 were assessed. Log-rank assessments of survival and median time to count recovery were carried out via Kaplan Meier survival analysis and group differences were assessed with Chi square or Fischer's exact test.

Results: A total of 199 pts who achieved a response (either complete remission [CR] or CR with incomplete count recovery [CRi]) to their first treatment of AML were included. 120 pts received CLAD/LDAC VEN; 79 pts received HMA/VEN. The median age was 72 yrs (range, 52 - 92) in GCSF vs 70 yrs (26 - 85) in no GCSF, p=0.009. 81 pts (41%) received GCSF anytime during their treatment: CLAD/LDAC/VEN (53/120, 44%); HMA/VEN (28/79, 35%). Reasons for GCSF administration included: enhance count recovery, n = 46 (57%); response to infection/FN, n = 28 (35%); unknown, n = 7 (9%). The median duration of C1 VEN for all pts was 21 days (7 - 28); during C2, 14 days (5 - 28). There were no significant differences in median C1 or C2 VEN duration, median bone marrow blast %, or ELN risk between GCSF vs no GCSF.

There was no significant difference in OS (median 24.7 vs. 50.72 months for GCSF vs no GCSF, p=0.8196) or RFS (median 19.1 vs. 28.1 months, p=0.8139). In multivariate analysis, GCSF was not prognostic for RFS (HR 1.064; 95% CI, 0.714-1.586; p=0.761) or OS (HR, 1.137; 95% CI, 0.739-1.751; p=0.559). Within 8 weeks, there were 2 deaths (1 bleeding complication; 1 septic shock) in GCSF and no deaths in no GCSF.

36 pts (18%) received GCSF during C1. In GCSF vs no GCSF, respectively median time to ANC >0.5 was 31 vs 28 days, p=0.048; median time to ANC >1 was 34 vs 32 days, p=0.234; median time to plt >50 was 28 vs 23 days, p=0.0002; median time to plt >100 was 30 vs 26 days, p=0.002. When evaluating pts who recovered ANC within 28 days, median time to ANC >1 was 24 days vs 27 days in GCSF vs no GCSF, p=0.031; more pts achieved ANC >1 with the use of GCSF (OR, 7.9; 95% CI, 1.002-62; p=0.050). By univariate analysis, the achievement of ANC >1 during C1 was favorable for RFS (HR, 0.447; 95% CI, 0.276-0.725; p=0.001) and OS (HR, 0.461; 95% CI, 0.279-0.760; p=0.002). The incidence of infection/FN during C1 for all pts was 20% (40/199); for patients receiving GCSF the incidence was 25% (9/36) vs. 19% (31/163) in no GCSF, p=0.4167.

187 pts proceeded to C2, during which 26 pts (14%) received GCSF. In GCSF vs no GCSF, respectively median time to ANC >0.5 was 43 vs 35 days, p=0.3585; median time to ANC >1 was 43 vs 39 days in, p=0.7359; median time to plt >50 was 86 vs 75 days, p=0.6462; median time to plt >100 was 152 days vs not reached, p=0.9491. The incidence of infection/FN during C2 for pts receiving GCSF was 3.9% (1/26) vs. 9.9% (16/161) in no GCSF, p=0.475.

Conclusion: In our cohort of pts receiving low intensity therapy for AML, GCSF appeared to be safe; we were able to demonstrate that there was no significant difference in OS or RFS between pts who did or did not receive GCSF. The use of GCSF appeared to enhance count recovery in pts, allowing more patients to reach an ANC>1 at the end of C1. The use of GCSF should be explored as a viable option to enhance count recovery and potentially mitigate infection in responding pts after receiving low-intensity chemotherapy.

Sasaki:Daiichi-Sankyo: Consultancy; Novartis: Consultancy, Research Funding; Enliven: Research Funding; Chugai: Other: Lecture fees; Otsuka: Other: Lecture fees; Pfizer: Consultancy. DiNardo:Loxo: Research Funding; Astex: Research Funding; Foghorn: Research Funding; Rigel: Research Funding; Amgen: Consultancy; Astellas: Consultancy, Honoraria; Gilead: Consultancy; ImmuneOnc: Research Funding; Servier: Consultancy, Honoraria, Other: meetingsupport, Research Funding; Cleave: Research Funding; Schrodinger: Consultancy, Honoraria; Riegel: Honoraria; Notable Labs: Honoraria; Immunogen: Honoraria; GSK: Consultancy, Honoraria; GenMab: Consultancy, Honoraria, Other: data safety board; Genetech: Honoraria; BMS: Consultancy, Honoraria, Research Funding; AstraZeneca: Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria; Stemline: Consultancy. 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