Cytotoxic therapy in acute myeloid leukemia: not quite dead yet

AbstractGiven the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients. Indeed, the future likely lies in combinations of therapies that act with a spectrum of mechanisms. Using a case-based format, this review will outline current treatment expectations for patients according to karyotypic risk and familiarize readers with the basis for common induction choices. Relapsed/refractory disease may be especially amenable to interventions with novel agents or clinical trials; however, there are still some patients who most benefit from intensive chemotherapy. This review will outline risk systems that help the practitioner identify those with the best chances for response and survival. Finally, clinical tools, including geriatric assessments and comorbidity calculators, may help clinicians recognize patients for whom disease risk and comorbidity tip the balance against classical chemotherapy, a frequent challenge for those who treat this devastating disease.

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Novel Agents for Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers10110429 ◽

2018 ◽

Vol 10 (11) ◽

pp. 429 ◽

Cited By ~ 11

Author(s):

Mario Luppi ◽

Francesco Fabbiano ◽

Giuseppe Visani ◽

Giovanni Martinelli ◽

Adriano Venditti

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Standard Of Care ◽

Gemtuzumab Ozogamicin ◽

Novel Agents ◽

Current Standard ◽

New Agents ◽

Emerging Treatments ◽

Approved Drugs ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. Recent advances in the understanding of AML pathogenesis have paved the way for the development of new agents targeting specific molecules or mechanisms that contribute to finally move beyond the current standard of care, which is “3 + 7” regimen. In particular, new therapeutic options such as targeted therapies (midostaurin and enasidenib), monoclonal antibodies (gemtuzumab ozogamicin), and a novel liposomal formulation of cytarabine and daunorubicin (CPX-351) have been recently approved, and will be soon available for the treatment of adult patients with AML. In this review, we will present and describe these recently approved drugs as well as selected novel agents against AML that are currently under investigation, and show the most promising results as monotherapy or in combination with chemotherapy. The selection of these emerging treatments is based on the authors’ opinion.

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Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape

Therapeutic Advances in Hematology ◽

10.1177/2040620717703012 ◽

2017 ◽

Vol 8 (6) ◽

pp. 185-195 ◽

Cited By ~ 6

Author(s):

Valeriy Sedov ◽

Robert K. Stuart

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Survival Rates ◽

Standard Of Care ◽

Initial Response ◽

Current Treatment ◽

Phase Iii ◽

Double Blind ◽

Poor Outcomes ◽

Acute Myeloid

Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy. There is no standard of care for relapsed/refractory (R/R) AML, and no new therapies have shown consistently superior outcomes in this setting in over two decades. Vosaroxin is an anticancer quinolone derivative (AQD) that was evaluated in combination with cytarabine for the treatment of R/R AML in the randomized, double-blind, placebo-controlled, phase III VALOR study ( n = 711). Compared with placebo/cytarabine, the vosaroxin/cytarabine regimen demonstrated favorable CR rates and survival in patients ⩾60 years of age, with toxicities similar to other AML regimens. Here we review outcomes of recent studies of commonly used chemotherapy regimens for the treatment of R/R AML and evaluate the results of the VALOR trial in the context of the current treatment landscape.

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Novel Approaches to the Treatment of Acute Myeloid Leukemia

Hematology ◽

10.1182/asheducation-2011.1.43 ◽

2011 ◽

Vol 2011 (1) ◽

pp. 43-50 ◽

Cited By ~ 51

Author(s):

Gail J. Roboz

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Molecular Genetic ◽

Treatment Strategies ◽

Standard Of Care ◽

The United States ◽

Current Treatment ◽

Treatment Standards ◽

Acute Myeloid

Abstract Approximately 12 000 adults are diagnosed with acute myeloid leukemia (AML) in the United States annually, the majority of whom die from their disease. The mainstay of initial treatment, cytosine arabinoside (ara-C) combined with an anthracycline, was developed nearly 40 years ago and remains the worldwide standard of care. Advances in genomics technologies have identified AML as a genetically heterogeneous disease, and many patients can now be categorized into clinicopathologic subgroups on the basis of their underlying molecular genetic defects. It is hoped that enhanced specificity of diagnostic classification will result in more effective application of targeted agents and the ability to create individualized treatment strategies. This review describes the current treatment standards for induction, consolidation, and stem cell transplantation; special considerations in the management of older AML patients; novel agents; emerging data on the detection and management of minimal residual disease (MRD); and strategies to improve the design and implementation of AML clinical trials.

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Clinical Features and Recurrence Pattern of Perianal Abscess in Patients with Acute Myeloid Leukemia

Acta Haematologica ◽

10.1159/000475589 ◽

2017 ◽

Vol 138 (1) ◽

pp. 10-13 ◽

Cited By ~ 4

Author(s):

Hung Chang ◽

Ming-Chung Kuo ◽

Tzung-Chih Tang ◽

Tung-Liang Lin ◽

Jin-Hou Wu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Gastrointestinal Tract ◽

Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Perianal Abscess ◽

Standard Of Care ◽

Recurrence Pattern ◽

Surgical Interventions ◽

Acute Myeloid

Introduction: Perianal abscess may develop during neutropenia periods in patients with acute myeloid leukemia (AML). The standard of care for perianal abscess in AML is unclear. Methods: We retrospectively collected patient data in our institute from 2009 to 2012. Results: Two hundred ninety-two patients with AML were analyzed. In total, 1,051 chemotherapy sessions were administered. Twenty-three patients experienced perianal abscess. Patients with perianal abscess were younger than those without (44 vs. 60 years, p < 0.0001). Perianal abscess developed in various phases of treatment and in the stem cell transplantation period. Twelve recurrences developed in 6 patients. Patients with a prior perianal abscess have a 10-fold risk of developing a subsequent abscess following further chemotherapy. The microbiology profile revealed that most pathogens were derived from the intestinal tracts, which was similar to the findings of previous studies. The 28-day mortality was 14.3% and the direct cause of death was not perianal abscess in any case. Surgical interventions had no impact on recurrence or survival. Conclusion: In patients with AML, perianal abscess results from gastrointestinal tract pathogens. Many patients do not require surgical interventions. The mortality is low but recurrence is common following subsequent chemotherapies. Therefore, awareness of recurrence is important for the timely management of perianal abscess in AML.

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Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

Biomarker Research ◽

10.1186/s40364-021-00288-7 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Xiang Zhang ◽

Jiejing Qian ◽

Huafeng Wang ◽

Yungui Wang ◽

Yi Zhang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Underlying Mechanism ◽

Lymphocytic Leukemia ◽

First Line ◽

Dominant Mutation ◽

First Line Therapy ◽

Line Therapy ◽

Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

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