Intensive consolidation in elderly AML patients – a phase IV study

On 17^th August 2017, in an article published in the American Journal of Hematology, Wolfgang R. Sperr, from the Medical University of Vienna, Wien, Austria, et al. reported results of their multi-center single arm phase IV study (EU Clinical Trials Register: 2007-005806-29), which aimed to assess the efficacy and feasibility of intensified consolidation in elderly patients with de novo Acute Myeloid Leukemia (AML). Additionally, the effect of pegfilgrastim (recombinant Granulocyte-Colony Stimulating Factor [G-CSF]) on neutropenia and hospitalization was also investigated.

Overall, 64 de novo AML patients were enrolled in this study between July 2008–November 2012. Thirty-nine patients (median age = 69.9 years) who achieved Complete Remission (CR) after induction chemotherapy were eligible for consolidation in this study. Patients were planned to receive intensive consolidation consisting of a 1^st cycle of FLAG with pegfilgrastim on day 6, 2^nd and 4^th consolidation cycle of Intermediate Dose cytarabine (IDAC) and pegfilgrastim on day 6 and the 3^rd cycle of IDAC was administered. All 4 planned consolidation cycles were administered in 59% of patients (23/39), 12.8%, 7.7%, 20.5% received three, two, and one cycles, 3/39 (7.7%) of consolidation therapy respectively.

The key results of the study were:

• Median duration of neutropenia in consolidation 1, 2, 3, and, 4; 9 vs 7 vs 11.5 vs 7.5 days 
• Probability of Overall Survival (OS) after 5 years was 32%
• OS was significantly better in patients that were < 75 years (n = 53) compared to patients that were ≥ 75 years (n = 11); P < 0.05

To evaluate the efficacy of pegfilgrastim, the authors compared consolidation cycles (2 and 4) where pegfilgrastim was given routinely on day 6 was compared to consolidation cycle 3 where pegfilgrastim was only used in case of infections and/or prolonged neutropenia. The key results were:

• Duration of neutropenia in patients (n = 17) differed significantly between consolidation 3 (11.5 days), consolidation 2 (7 days), and consolidation 4 (7.5 days), P < 0.05
• Duration of hospitalization in patients differed significantly between consolidation 3 (29 days), consolidation 2 (20 days), and consolidation 4 (22 days), P < 0.05

Sperr et al. concluded by stating that “intensified consolidation can be safely administered in AML patients aged ≥60 years and resulted in an improved survival”. Additionally, patients aged <75 years seem to benefit from this strategy.

Furthermore, addition of pegfilgrastim during consolidation shortened the duration of neutropenia and the duration of hospitalization significantly.

Abstract

The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization-time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction-chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation-cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (P < .05). Median overall survival was 1.1 years and differed significantly between patients aged <75 and ≥75 years (P < .05). The probability to be alive after 5 years was 32%. Together, intensified consolidation can be administered in AML patients ≥60, and those who are <75 may benefit from this therapy. Routine administration of pegfilgrastim during consolidation shortens the time of neutropenia and hospitalization in these patients.