Can the New and Old Drugs Exert an Immunomodulatory Effect in Acute Myeloid Leukemia?

Abstract

Acute myeloid leukemia (AML) is considered an immune-suppressive neoplasm capable of evading immune surveillance through cellular and environmental players. Increasing knowledge of the immune system (IS) status at diagnosis seems to suggest ever more attention of the crosstalk between the leukemic clone and its immunologic counterpart. During the last years, the advent of novel immunotherapeutic strategies has revealed the importance of immune dysregulation and suppression for leukemia fitness. Considering all these premises, we reviewed the “off-target” effects on the IS of different drugs used in the treatment of AML, focusing on the main advantages of this interaction. The data reported support the idea that a successful therapeutic strategy should consider tailored approaches for performing leukemia eradication by both direct blasts killing and the engagement of the IS.

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

“…Otherwise, it can be explained that the higher dose of ATG used in HID transplantation, compared with MSD or UD transplantation, in our study could be a cause of the more frequent CMV infections, which is supported by recent data showing a similar frequency of CMV infections in MUD and HID when using the same RIC regimen and ATG dose [ 36 ]. Nevertheless, despite concerns about the immunosuppressive effects of venetoclax [ 37 , 38 ], the incidence of CMV infection observed in this study was not higher than that with post-IC transplantation reported in other studies [ 20 , 28 , 35 ]. As suggested with GVHD complications, traditional risk factors, such as donor type and ATG dosage, are likely to play a greater role in the occurrence of post-transplant infectious complications than the regimens used prior to allo-HCT.…”

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

“…Traditionally, new drugs have been tested in newly diagnosed cases of acute myeloid leukemia with relapse or at risk of disadvantage [ 12 , 49 – 51 ]. One possibility is on the MRD setting.…”

Doxorubicin Activity Is Modulated by Traditional Herbal Extracts in a 2D and 3D Multicellular Sphere Model of Leukemia

“…Treatments for AL are focused on the direct elimination of tumor cells and, more recently, on the activating of the antitumor immune response [ 22 , 23 ]. However, other therapies, such as phytomedicines, can have a simultaneous effect on leukemic and microenvironment cells due to their multimolecular nature [ 24 , 25 , 26 ]; furthermore, in synergy with conventional therapy, they can improve the therapeutic response by reducing its toxicity and limiting the secondary effects of chemotherapy [ 27 , 28 , 29 ].…”