Alternative novel therapies for the treatment of elderly acute myeloid leukemia patients

Abstract

With a median age at diagnosis of approximately 65–70 years, acute myeloid leukemia (AML) represents a major therapeutic challenge in the elderly. Only 30–35% of elderly patients with AML are considered eligible for intensive chemotherapy and do actually receive it. However, the long-term benefit associated with intensive chemotherapy remains marginal, and the overall outcome for this population remains poor. The remaining 60–65% of elderly AML patients receives supportive care only. Nevertheless, several studies have indicated that patients who receive any therapy had a better outcome if compared with patients who receive supportive care only. Thus, the development of novel, less toxic, targeted agents is offering new options to older AML patients who are unfit for intensive approaches. In the present review, we will report on the results achieved using intensive chemotherapy and novel agents, and will describe some of the new strategies under development for treating older AML patients.

Keywords::

• acute myeloid leukemia
• comorbidities
• elderly patients
• intensive therapy
• low-dose therapy
• novel agents
• prognostic factors
• transplantation

Acknowledgements

We thank N Musco and L Isidori for editing the English style of the manuscript free of any charge.

Financial & competing interests disclosure

The authors were supported in part by AIL Pesaro Onlus. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Acute myeloid leukemia (AML) presents at all ages, but is for the most part a disease of the elderly.

• • The adverse prognostic impact of older age is generally attributable to the concurrence of adverse disease-related features (e.g., poor cytogenetics, secondary AML, multidrug resistance phenotype) and poor patients-related factors (e.g., general conditions, organ dysfunctions and comorbidities).

• • No currently available treatment option for older patients with AML has demonstrated a survival advantage over any other.

• • Although complete remission rates of 40–80% can be achieved with intensive chemotherapy, in highly selected populations, long-term survival is extremely poor, with less than 10% of patients being alive at 2 years.

• • The 2-year overall survival (OS) data clearly indicate that elderly patients with AML have a very poor outcome, stressing the need of identifying less toxic and more successful therapies for this population.

• • No prospective, randomized clinical trials have been conducted on autologous stem cell transplantation (ASCT), and therefore should be limited only to selected patients.

• • With the use of reduced-intensity conditioning (RIC) regimens, allogeneic transplantation has become a valid option at least for patients up to 70 years in first complete response (CR).

• • The development of new drugs such as monoclonal antibodies, hypomethylating agents (HMAs), immunomodulatory and targeted drugs, is depicting a new scenario with novel magic bullets available for the treatment of elderly AML patients.

• • The progress in genomics suggests a wider and wider application of personalized therapies, although, up to now, a possible winner, or a group of possible winners, have not yet been identified among the available molecules.

• • A major hope, in a future years view, could be reserved to the immune modulation of the clonal evolution of the disease.