There were 124 evaluable patients with 4 deaths during induction (1 myocardial ischaemia, 2 intracerebral haemorrhage, 1 cerebral oedema), while 2 withdrew from study during induction. The remaining 118/124 (95%) entered haematological complete remission (hCR). 112/118 hCR patients proceeded to consolidation, each of whom attained molecular remission. 2/112 patients relapsed after completion of consolidation, one with initial molecular relapse after 166 days (followed by CNS relapse and death) and one with molecular relapse after 189 (dying from sepsis during salvage therapy).
This equates to a freedom from relapse (FFR) of 97.5% and overall survival (OS) of 93.2%. Age did not correlate with FFR or OS. The failure free survival (FFS) of 88.1% was a composite measure of time from commencement of ATRA therapy to the earliest of treatment failure (failure to achieve molecular CR or withdrawal of protocol therapy for any reason), relapse, or death. The results compared favorably with the group’s prior APML3 study which used ATRA and idarubicin (but no arsenic) in induction and consolidation.r
Comparison of APML4 with APML3 (historic control). (C) FFS.
© Blood 2012
Maintenance therapy in low/intermediate risk patients
A separate cooperative group phase III non-inferiority study (SWOG 0521) was conducted to examine the need for maintenance therapy in patients with low/intermediate risk APML. The primary end point was 3-year disease free survival. The study was closed to new enrolment prematurely (105 patients enrolled of the intended 400) due to slow accrual. However, there were no relapses amongst the randomised patients.r
Further studies in the role of maintenance therapy in patients with low/intermediate risk disease achieving molecular remission post ATRA or ATO containing consolidation regimens, may need to be explored.r