Original StudySalvage Therapy Outcomes in a Historical Cohort of Patients With Relapsed or Refractory Acute Myeloid Leukemia
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.
References (22)
Relapsed acute myeloid leukemia: why is there no standard of care?
Best Pract Res Clin Haematol
(2013)- et al.
Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation
Blood
(2013) - et al.
Decitabine and sorafenib therapy in FLT-3 ITD-mutant acute myeloid leukemia
Clin Lymphoma Myeloma Leuk
(2015) - et al.
Quantifying the survival benefit for allogeneic hematopoietic stem cell transplantation in relapsed acute myelogenous leukemia
Biol Blood Marrow Transplant
(2009) - et al.
Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia
Blood
(2017) - et al.
Spotlight on midostaurin in the treatment of FLT3-mutated acute myeloid leukemia and systemic mastocytosis: design, development, and potential place in therapy
Onco Targets Ther
(2018) - et al.
Outcome of patients with acute myelogenous leukemia after second salvage therapy
Cancer
(2005) - et al.
Outcome of relapsed or refractory acute myeloid leukemia treated with intensive salvage chemotherapy in real life in comparison to intermediate dose cytarabine in phase 3 studies
Leuk Lymphoma
(2019) - et al.
Results of second salvage therapy in 673 adults with acute myelogenous leukemia treated at a single institution since 2000
Cancer
(2018) - et al.
Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia
J Clin Oncol
(2004)