Receipt of Maintenance Therapy Is Most Predictive of Survival in Older Acute Lymphoblastic Leukemia Patients Treated with Intensive Induction Chemotherapy Regimens.

Abstract

AbstractAbstract 2600 Background:Older patients diagnosed with acute lymphoblastic leukemia (ALL) receiving intensive induction therapy often suffer from poor outcomes due to therapy-related toxicity and high rates of relapse. We previously reported that patients age ≥60 diagnosed with ALL and treated at our institution with either hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine (hyperCVAD) or daunorubicin, vincristine and prednisone (DVP) induction therapies achieved comparable rates of survival. Now with longer follow-up and further analysis, we describe additional outcomes and factors predictive of survival in this patient population. Methods:Thirty-seven patients diagnosed with ALL at age ≥60 and treated at the University of Pennsylvania between July 2003 and June 2011 who received induction therapy with either hyperCVAD (≥1 A+B cycle) or DVP (phase I+II) were analyzed. HyperCVAD was administered as first described at the MD Anderson Cancer Center and DVP per the ECOG 2993/UKALL XII protocol. Therapy adjustments and bone marrow biopsy to confirm remission were performed at the discretion of the treating physician. Almost all Philadelphia chromosome (Ph) positive patients received a tyrosine kinase inhibitor. Event-free survival (EFS) was defined as the time from diagnosis to either relapse or death from any other cause. Results:Table 1 describes baseline characteristics. Table 2 describes outcomes. If achieved, morphologic remission was recognized upon the first bone marrow assessment performed while on therapy, which occurred after a median of 4 (2 A+B) cycles of hyperCVAD and by completion of phase II induction of DVP. EFS and overall survival (OS) trended in favor of DVP. HyperCVAD patients were more likely to complete intensive therapy but less likely to receive maintenance therapy, and more likely to relapse with the majority of relapses occurring off active treatment. Primary reasons for not starting or stopping maintenance therapy were infections and cytopenias. Relapsed disease was the most frequent cause of death. Table 3 describes univariate Cox regression analysis. Receipt of maintenance therapy demonstrated the strongest association with survival (p=0.0001, hazard ratio 0.06 for EFS; p=0.0002, hazard ratio 0.05 for OS). Valid multivariate analysis could not be performed due to small sample size. Conclusions:In older ALL patients treated with aggressive induction therapies and achieving remission, receipt of maintenance therapy appears to be most predictive of EFS and OS. Outcomes in the DVP and hyperCVAD groups were similar although a trend towards prolonged survival in the DVP group was seen, which may be explained by a lower rate of relapse due to a higher likelihood of remaining on therapy over time. Our findings suggest that these patients may benefit from attenuated courses of intensive initial therapy in order to avoid developing toxicities that may prohibit tolerance of prolonged maintenance therapy.Table 1– Baseline characteristicsFactorAll (n=37)DVP (n=13)HyperCVAD (n=24)p valueMeidan age at diagnosis (years)6464641.0%Age ≥653231331.0%Ph positive3862250.04%High-risk WBC (≥30×103 cells/μL if B-cell, ≥100×103 cells/μL if T-cell)3031291.0Table 2- OutcomesFactorAllDVPHyperCVADp value%Complete response9292921.0%Relapse5642640.29%Completion of intensive therapy (hyperCVAD x8 or DVP induction/intensification/consolidation), if remitting3817500.07%Receipt of any post-remission therapy91100850.28%Receipt of any maintenance therapy, if intended7991720.36%Off treatment at relapse (if not having completed maintenance)5925690.25Median length of follow-up (months)17.232.817.00.10Median EFS (months)14.944.513.80.06%EFS at 2 years3054170.028Median OS (months)18.167.317.30.07%OS at 2 years3554250.15Table 3– Univariate Cox regression analysisFactorEFSOSp valueHazard ratiop valueHazard ratioAge >65 vs. ≤650.60-0.36-Ph(+) vs. Ph(-)0.87-0.79-High-risk WBC vs. low-risk0.68-0.80-DVP vs. hyperCVAD, all0.06-0.07-DVP vs. hyperCVAD, if remitting0.06-0.06-Completion of intensive therapy (hyperCVAD x8 or DVP induction/intensification/consolidation) vs. not, if remitting0.14-0.22-Receipt of any post-remission therapy vs. none0.0020.120.010.17Receipt of any maintenance therapy vs. none, if intended0.00010.060.00020.05 Disclosures:No relevant conflicts of interest to declare.