Given the high rate of relapse, there is rationale and need for post remission maintenance therapy to mitigate this risk. However with the recent completion of the QUAZAR AML-001 clinical study and FDA approval of CC-486 (oral azacitidine) this paradigm maybe set to change ( 21). The current standard of care for most patients with AML achieving a CR with induction and consolidation is observation without maintenance therapy, with the exception of acute promyelocytic leukemia where maintenance arsenic trioxide and retinoic acid have shown clear benefit ( 19, 20). A major reason for the success of alloSCT in maintenance of remission and cure of AML is through the generation of allo-reactive T cells and graft versus leukemia (GVL) effect ( 16– 18).
The most effective post remission therapy in AML continues to be alloSCT, but is not available to all patients with high-risk disease because high rates of complications limit broad applicability to patients with multiple comorbidities and some patients lack suitable donors ( 8, 13– 15). Patients with high risk AML that are ineligible for allogeneic hematopoietic stem cell transplantation (alloSCT) continue to have poor outcomes and low likelihood of cure ( 12). There is a critical need for therapeutic strategies that decrease this relapse risk and improve the survival of patients with AML. Despite these successes, relapse remains a major concern with relapse risk greater than 50% for all adults with high risk AML ( 9– 11). Consolidation therapy helps to eradicate residual leukemia and reduces the risk of disease relapse ( 2, 7, 8). For example, dose intensification and novel drug combinations during induction therapy have led to higher response rates and improved survival in patients with newly diagnosed AML ( 1– 6). In this review we summarize prior and ongoing maintenance therapy approaches in AML and highlight some of the most promising strategies.Īdvances in therapeutics and supportive care for acute myeloid leukemia (AML) have led to steady improvements in the outcomes for patients with AML. Ongoing and future studies will continue to elucidate the true role for maintenance therapy options in patients with AML. Recent strategies, especially with hypomethylating agents have begun to show promise as maintenance therapy in improving clinical outcomes.
Overall, the evidence in favor of maintenance therapy is limited. These approaches have included cytotoxic chemotherapy, immunotherapy, hypomethylating agents, and targeted small molecule therapy. For decades, investigators have attempted strategies of maintenance therapy to prolong both remission duration and overall survival in patients with AML. Despite these advances, even in patients that achieve a complete remission with initial therapy high rates of relapse remain a clinical dilemma. Recent advances in therapeutics coupled with steady improvements in supportive care for patients with acute myeloid leukemia (AML) have led to improved outcomes. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, United States.© 2019 by The American Society of Hematology. Outcomes from ongoing clinical trials for BPDCN can be evaluated relative to this contemporary cohort. This study highlights poor outcomes for patients with BPDCN in the modern era and the need for new treatments. We also identified disease responses to pralatrexate and enasidenib in some patients. Clinical characteristics at diagnosis associated with poorer outcomes included age >60 years, abnormal karyotype, and terminal deoxynucleotidyltransferase (TdT) negativity in the BPDCN cells. Only 55% of patients received intensive chemotherapy, and 42% of patients underwent stem cell transplantation. Intensive first-line therapy and "lymphoid-type" chemotherapy regimens were associated with better outcomes. In 59 studied patients with BPDCN, the median overall survival from diagnosis was 24 months, and outcomes were similar in patients with "skin only" or with systemic disease at presentation.
We therefore sought to define the clinical characteristics and outcomes of a group of patients with BPDCN treated at 3 US cancer centers in the modern era but before tagraxofusp was available. However, because there was no matched internal comparator in this or any clinical study to date, results of BPDCN trials testing new drugs are difficult to compare with alternative therapies. The interleukin-3 cytotoxin conjugate tagraxofusp was recently tested in phase 1/2 trials that led to US Food and Drug Administration approval, the first ever for BPDCN. Existing data on the clinical behavior of BPDCN are limited because reported outcomes are from small retrospective series, and standardized treatment guidelines are lacking. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy with poor outcomes.
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