Original Study
Salvage Therapy Outcomes in a Historical Cohort of Patients With Relapsed or Refractory Acute Myeloid Leukemia

https://doi.org/10.1016/j.clml.2020.06.007Get rights and content

Abstract

Background

The prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is poor, with no universal standard salvage therapy currently available for most patients. Novel therapies with efficacy in patient subsets often have limited activity in alternative subsets, resulting in a majority of patients not gaining benefit from these therapies. This study systematically evaluated patient outcomes in a large cohort of R/R AML patients from a single institution across all salvage therapy lines, up to and including the third line.

Patients and Methods

Outcomes of R/R AML patients treated at a single institution (MD Anderson Cancer Center, Houston, TX) between 2002 and 2016 were entered into a central database. Eligible patients received one or more lines of salvage therapy after first occurrence of R/R AML. Patients who received second- or third-line salvage treatment were also included in the first salvage analysis. Eligible patients were ≥ 18 years old at time of initial AML diagnosis, with no central nervous system involvement.

Results

A total of 818 eligible patients received one or more lines of salvage therapy, 809 received second-line salvage therapy, and 397 received third-line salvage therapy. Complete remission rates decreased from 14% after first salvage therapy to 9% after second salvage therapy and 3% after third salvage therapy. Median overall survival was 6.30, 4.07, and 2.98 months after first, second, and third salvage therapies, respectively.

Conclusion

These data indicate that the best chance of obtaining long-term remission in AML is with a successful first induction. Strategies that improve initial response and decrease the likelihood of relapse should be pursued.

Introduction

The prognosis of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) is poor, with no universal standard salvage therapy currently available for most of these patients.1 Until recently, most clinical trials of investigational agents in patients with R/R AML accrued patients with a variety of disease characteristics. Salvage therapy options for these patients may improve long-term outcomes when patient subsets with well-defined molecular and cellular pathways are identified and therapeutically targeted.1

Novel therapies that show efficacy in specific patient subsets often have limited or no activity in alternative patient subsets, resulting in a majority of patients not gaining any benefit from these therapies as a result of a lack of efficacy.2 Furthermore, there is great variability in the regimens used across treatment centers and in clinical trials, making outcomes assessments for specific regimens difficult; often, studies only assess outcomes after a specific line of salvage therapy, not across multiple salvage therapy lines.3, 4, 5 In addition, outcomes from subsequent salvage therapies can be difficult to assess because of various factors that may influence these results; for example, second salvage treatment outcomes can be dependent on the regimen received in the first line of salvage therapy.

The aim of this study was to systematically evaluate patient outcomes in a large cohort of R/R AML patients from a single institution across all salvage treatment lines, up to and including the third line. These insights are expected to provide robust efficacy benchmarks for existing salvage therapies in R/R AML and inform the development of more effective therapies in this patient population.

Section snippets

Patient Population

Patients in this study were treated for R/R AML at a single institution (MD Anderson Cancer Center, Houston, TX) between 2002 and 2016. All clinical investigations were conducted in accordance with the Declaration of Helsinki and were approved by the institutional human research committee.

All data were prospectively entered into and maintained in a central database used for this analysis. Patients had experienced at least one prior treatment failure and had received at least one line of salvage

Results

A total of 818 eligible patients received at least one line of salvage therapy; 809 received second-line treatment, and 397 received third-line treatment. In general, baseline characteristics were balanced across salvage treatment lines (Table 1). The proportion of patients with baseline age at initial diagnosis less than 60 years increased with number of salvage treatment regimens received (first, 45%; second, 51%; third, 59%).

Overall, CR rates decreased from 14% after first salvage to 9%

Discussion

The National Comprehensive Cancer Network (NCCN) Guidelines for acute myeloid leukemia (version 3.2018) provide a comprehensive list of recommended regimens for a variety of R/R AML patient subgroups.9 The regimens recommended in the NCCN guidelines align with many of the regimens received by patients included in this analysis, including aggressive therapies containing HD cytarabine, less aggressive LD cytarabine-based regimens with hypomethylating agents, hypomethylating agents with FLT3

Conclusion

Overall, few R/R AML patients were able to achieve subsequent CR after second treatment failure or relapse. EFS was very short—typically less than 2 months, and almost invariably less than 6 months, due to most patients failing to achieve CR. Even at first salvage, median OS was only a little more than 6 months, and 74% of patients had died of disease by 1 year. In conjunction with evidence that some patients achieve long-term remission with first-line induction therapy, these data strongly

Disclosure

F.R. discloses the following: Sunesis: honoraria; Jazz: honoraria; Macrogenix: honoraria, research funding; AbbVie: research funding; Orsenix: honoraria; Bristol-Myers Squibb: research funding; Seattle Genetics: research funding; Xencor: research funding; Astellas Pharmaceuticals: consultancy, honoraria; Amgen: honoraria, research funding, speakers bureau. T.K. discloses the following: Pfizer: consultancy, research funding; Amgen: consultancy, research funding; BMS: research funding; AbbVie:

Acknowledgments

Funded by Amgen Inc. The authors wish to thank James Ziobro (funded by Amgen) for providing medical writing assistance.

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