Contributions
Abstract: EP439
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Patients (pts) with acute myeloid leukemia (AML) who are older or ineligible for intensive chemotherapy have low remission rates and poor survival. In the phase 3, randomized, placebo (Pbo)‑controlled VIALE-C study (NCT03069352), median overall survival was 8.4 mo with venetoclax (Ven) + low-dose cytarabine (LDAC) vs 4.1 mo with Pbo+LDAC in older or unfit pts with newly diagnosed AML (Blood. 2020;135:2137-45).
Aims
To analyze the frequency and management of cytopenia in pts who achieved a best response of complete remission (CR) or CR with incomplete count recovery (CRi) in VIALE-C.
Methods
Enrolled pts had newly diagnosed AML and were ineligible for intensive chemotherapy due to age (≥75 y) or comorbidities. Pts were randomized 2:1 to once-daily 600 mg oral Ven or Pbo in 28-day cycles plus 20 mg/m2 subcutaneous LDAC on Days 1–10. After pts achieved blast clearance (bone marrow blasts <5%), dose modifications were used to manage cytopenia (Table 1). Cytopenia was defined as Grade 4 neutropenia (absolute neutrophil count <500/μL) or Grade 4 thrombocytopenia (platelet count <25×103/μL) lasting ≥7 days and was assessed using laboratory data.
Results
Of randomized pts who received Ven+LDAC (n=142) and Pbo+LDAC (n=68), 69 (49%) and 9 (13%), respectively, achieved a best response of CR/CRi. Of 69 pts in CR/CRi in the Ven+LDAC arm, cumulatively, 74%, 84%, 88%, 97%, and 99% achieved blast clearance by the end of Cycles 1, 2, 3, 4, and ≥7, respectively (1 pt achieved clearance after treatment discontinuation). Of 9 pts in CR/CRi in the Pbo+LDAC arm, cumulatively, 33%, 56%, 56%, 89%, and 100% achieved blast clearance by the end of Cycles 1, 2, 3, 4, and ≥7, respectively. After achieving blast clearance, delayed start of the next cycle to allow for count recovery occurred in 71% and 44% of pts in the Ven+LDAC and Pbo+LDAC arms, respectively, with a median delay (min-max) to the next cycle of 8 (2–31) and 3 (2–7) days, respectively. More pts in CR/CRi who received Ven+LDAC vs Pbo+LDAC had postremission cytopenia (75% vs 33%). The proportion of pts in CR/CRi with in-cycle dose interruptions (ie, days without Ven/Pbo exposure between a cycle’s first and last Ven/Pbo dose) was similar between arms (Ven+LDAC, 22%; Pbo+LDAC, 22%), with a median duration (min-max) of 3 days (1–12) for Ven+LDAC and 5 days (1–10) for Pbo+LDAC. A greater proportion of pts in CR/CRi who received Ven+LDAC vs Pbo+LDAC experienced postremission cycle delays due to cytopenia (62% vs 33%). More pts in CR/CRi had postremission reductions in Ven/Pbo dosing days and/or within cycle dose interruptions totaling ≥7 days due to cytopenia in the Ven+LDAC arm (61%) vs the Pbo+LDAC arm (22%). Of these pts, the median percentage of days (min-max) without Ven or Pbo administration while in remission (out of the total no. of remission days) was 14% (1–73) in the Ven+LDAC arm and 7% (4–9) in the Pbo+LDAC arm. Ultimately, 29 pts in CR/CRi (42%) in the Ven+LDAC arm and 1 (11%) pt in the Pbo+LDAC arm received ≤21-day Ven/Pbo dosing postremission, with a median (min-max) time from remission to first ≤21-day cycle of 71 days (1–339) for Ven+LDAC and 1 day (1–1) for Pbo+LDAC.
Conclusion
In this study, bone marrow blast clearance for responding pts at the end of Cycle 1 was higher among pts who received Ven+LDAC (74%) vs Pbo+LDAC (33%). Although postremission cytopenia and dose modifications were more frequent with Ven+LDAC, cytopenia was successfully managed with dose modifications, representing an important practice consideration in helping pts to prolong disease control.
Keyword(s): Acute myeloid leukemia, Adult, Myelosuppression
Abstract: EP439
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Patients (pts) with acute myeloid leukemia (AML) who are older or ineligible for intensive chemotherapy have low remission rates and poor survival. In the phase 3, randomized, placebo (Pbo)‑controlled VIALE-C study (NCT03069352), median overall survival was 8.4 mo with venetoclax (Ven) + low-dose cytarabine (LDAC) vs 4.1 mo with Pbo+LDAC in older or unfit pts with newly diagnosed AML (Blood. 2020;135:2137-45).
Aims
To analyze the frequency and management of cytopenia in pts who achieved a best response of complete remission (CR) or CR with incomplete count recovery (CRi) in VIALE-C.
Methods
Enrolled pts had newly diagnosed AML and were ineligible for intensive chemotherapy due to age (≥75 y) or comorbidities. Pts were randomized 2:1 to once-daily 600 mg oral Ven or Pbo in 28-day cycles plus 20 mg/m2 subcutaneous LDAC on Days 1–10. After pts achieved blast clearance (bone marrow blasts <5%), dose modifications were used to manage cytopenia (Table 1). Cytopenia was defined as Grade 4 neutropenia (absolute neutrophil count <500/μL) or Grade 4 thrombocytopenia (platelet count <25×103/μL) lasting ≥7 days and was assessed using laboratory data.
Results
Of randomized pts who received Ven+LDAC (n=142) and Pbo+LDAC (n=68), 69 (49%) and 9 (13%), respectively, achieved a best response of CR/CRi. Of 69 pts in CR/CRi in the Ven+LDAC arm, cumulatively, 74%, 84%, 88%, 97%, and 99% achieved blast clearance by the end of Cycles 1, 2, 3, 4, and ≥7, respectively (1 pt achieved clearance after treatment discontinuation). Of 9 pts in CR/CRi in the Pbo+LDAC arm, cumulatively, 33%, 56%, 56%, 89%, and 100% achieved blast clearance by the end of Cycles 1, 2, 3, 4, and ≥7, respectively. After achieving blast clearance, delayed start of the next cycle to allow for count recovery occurred in 71% and 44% of pts in the Ven+LDAC and Pbo+LDAC arms, respectively, with a median delay (min-max) to the next cycle of 8 (2–31) and 3 (2–7) days, respectively. More pts in CR/CRi who received Ven+LDAC vs Pbo+LDAC had postremission cytopenia (75% vs 33%). The proportion of pts in CR/CRi with in-cycle dose interruptions (ie, days without Ven/Pbo exposure between a cycle’s first and last Ven/Pbo dose) was similar between arms (Ven+LDAC, 22%; Pbo+LDAC, 22%), with a median duration (min-max) of 3 days (1–12) for Ven+LDAC and 5 days (1–10) for Pbo+LDAC. A greater proportion of pts in CR/CRi who received Ven+LDAC vs Pbo+LDAC experienced postremission cycle delays due to cytopenia (62% vs 33%). More pts in CR/CRi had postremission reductions in Ven/Pbo dosing days and/or within cycle dose interruptions totaling ≥7 days due to cytopenia in the Ven+LDAC arm (61%) vs the Pbo+LDAC arm (22%). Of these pts, the median percentage of days (min-max) without Ven or Pbo administration while in remission (out of the total no. of remission days) was 14% (1–73) in the Ven+LDAC arm and 7% (4–9) in the Pbo+LDAC arm. Ultimately, 29 pts in CR/CRi (42%) in the Ven+LDAC arm and 1 (11%) pt in the Pbo+LDAC arm received ≤21-day Ven/Pbo dosing postremission, with a median (min-max) time from remission to first ≤21-day cycle of 71 days (1–339) for Ven+LDAC and 1 day (1–1) for Pbo+LDAC.
Conclusion
In this study, bone marrow blast clearance for responding pts at the end of Cycle 1 was higher among pts who received Ven+LDAC (74%) vs Pbo+LDAC (33%). Although postremission cytopenia and dose modifications were more frequent with Ven+LDAC, cytopenia was successfully managed with dose modifications, representing an important practice consideration in helping pts to prolong disease control.
Keyword(s): Acute myeloid leukemia, Adult, Myelosuppression