Combination Therapy with Immune Checkpoint Inhibitors and Histone Deacetylase Inhibitors or Alkylating Agents

Area of Science:

• Oncology
• Cancer Research
• Immunotherapy

Background:

• Immune checkpoint inhibitors (CPIs) are established treatments for numerous cancers.
• Histone deacetylase inhibitors (HDACis) and alkylating agents (AAs) may enhance CPI efficacy.
• Understanding potential synergistic interactions is crucial for advancing cancer therapy.

Purpose of the Study:

• To conduct a comprehensive literature review on the synergistic activity of CPIs combined with AAs and/or HDACis.
• To explore the potential of these combinations in various malignancies.
• To identify patterns in concomitant versus sequential administration strategies.

Main Methods:

• Systematic literature search of PubMed and oncology congress abstracts.
• Inclusion of clinical and non-clinical studies on CPIs, AAs, and HDACis.
• Classification of studies by agent type, tumor entity, and treatment sequence.

Main Results:

• 227 unique clinical studies were identified across solid tumors and hematological malignancies.
• Randomized trials combining CPIs with AAs showed superior outcomes compared to monotherapy.
• Combination therapy with CPIs and HDACis demonstrated promising anti-cancer activity.

Conclusions:

• Sequential or concomitant CPIs with AAs or HDACis may improve patient outcomes across diverse tumor types.
• There is a strong rationale for further investigation into CPI, AA, and HDACi synergy.
• These combinations represent a promising avenue for future cancer treatment strategies.