Condensed HDAC Schedule Superior to Standard Schedule in AML
Consolidation therapy with a condensed schedule of high-dose cytarabine is superior to a standard schedule.
SAN DIEGO – Among patients with acute myeloid leukemia (AML), consolidation therapy with a condensed schedule of high-dose cytarabine (HDAC) is superior to a standard schedule with respect to hematologic recovery, infection rate, and length of hospitalization, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1
"Repetitive cycles of higher doses of cytarabine 0.5 to 3 g/m2 administered over 3 to 6 days have been widely used for conventional intensive consolidation therapy of acute myeloid leukemia," said principal investigator Sonia Jaramillo, MD, a physician at University Hospital Ulm, Germany. “There remain open questions regarding the most appropriate schedule, dose, and number of cycles.”
The researchers compared a compressed schedule of high-dose cytarabine on days 1, 2, and 3 with standard HDAC given on days 1, 3, and 5, and evaluated the prophylactic use of pegfilgrastim after chemotherapy among patients in first complete remission receiving repetitive consolidation cycles for AML.
The investigators included 568 patients who were randomly assigned up-front 1:10 between the standard German intergroup-arm the AMLSG 07-04 study (Clinical Trials.gov Identifier: NCT00151242). Patients in AMLSG 07-04 received induction therapy consisting of 2 cycles of idarubicin, cytarabine, and etoposide with or without all-trans retinoic acid (ATRA).
For consolidation therapy, patients with high-risk AML were assigned to receive allogeneic hematopoietic cell transplantation. All other patients were assigned to 3 cycles of cytarabine 3g/m² twice daily on days 1, 3, 5 and pegfilgrastim on day 10 (HDAC-135) and or a condensed schedule with cytarabine 3g/m² twice daily on days 1,2,3 and pegfilgrastim on day 8 (HDAC-123). Patients randomly assigned into the German AML intergroup arm were treated with cytarabine 3g/m² twice daily on days 1, 3, 5 (HDAC-135) without prophylactic growth-factor support.
Time from start to chemotherapy until hematologic recovery with leukocytes greater than 1.0 g/L and neutrophils greater than 0.5 g/L was significantly (P < .0001 for both) shorter among patients receiving HDAC-123 compared with those given HDAC-135.
Time from chemotherapy initiation until hematologic recovery was further reduced by 2 days (P < .0001) with the addition of pegfilgrastim.
Rates of infection (P < .0001), length of hospitalization, and platelet transfusions were significantly reduced in patients receiving HDAC-123 vs HDAC-135, and rates of infections was significantly lower with added pegfilgrastim (P = .002).
“In this prospective study, we found that high-dose cytarabine administered on days 1, 2, and 3 compared with high-dose cytarabine given on days 1, 3, and 5 resulted in shorter white blood cell and neutrophil recovery, fewer platelet transfusions, lower infection rate, and fewer days in hospital,” said Dr Jaramillo.
“Pegfilgrastim growth factor support resulted in shorter white blood cell and neutrophil count recovery, lower infection rate, and fewer days in hospital,” Dr Jaramillo added.
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There were no significant differences in relapse-free survival (P = .48) or overall survival (P = .90) between the 2 groups.
“When using higher doses of cytarabine for consolidation therapy in younger adult patients with AML, administration of cytarabine on days 1, 2, and 3 every 12 hours appears to be the preferred treatment schedule, resulting in faster hematologic recovery, lower infection rate, and fewer days in the hospital,” concluded Dr Jaramillo. “Administration of pegfilgrastim may further reduce the rate of infections and duration of hospitalization.”
- Jaramillo S, Benner A, Krauter J, et al. Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim growth factor support in acute myeloid leukemia. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.