Comparing targeted therapy and chemoimmunotherapy as a frontline treatment for chronic lymphocytic leukemia and small lymphocytic lymphoma

This review aimed to compare the benefits and risks associated with targeted therapy (TT) and chemoimmunotherapy (CIT) as frontline treatments for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). 

The number of treatment options for CLL and SLL has increased in the last few years. For a long time, first line treatment included CIT with rituximab (Rituxan). This treatment increases the response of the immune system to attack and kill cancer cells. 

During recent years, TT with or without immunotherapy has emerged as the new standard for front-line treatment of CLL/SLL. These TTs target and block certain proteins on B cells (immune cells) that help cancer cells survive. This leads to cancer cells to die. The benefits and risks associated with TT and CIT as frontline treatments for CLL/SLL are still unknown.  

Recently published clinical trials on frontline CLL/SLL treatment were reviewed with a focus on comparing CIT and TT. 

Immunotherapy drugs such as rituximab and obinutuzumab (Gazyva) added to chemotherapy regimens resulted in improved survival without cancer worsening in patients with CLL/SLL.

TTs such as ibrutinib (Imbruvica) or acalabrutinib (Calquence) as continuous treatment with or without immunotherapies have given similar or better outcomes compared to conventional CIT regimens in previously untreated patients with CLL/SLL regardless of age and other medical conditions. 

Another important TT drug used in patients with CLL/SLL is venetoclax (Venclexta). Venetoclax combined with immunotherapies for a fixed duration of time showed a good effectiveness in patients with CLL/SLL. Newer TT drugs such as idelalisib (Zydelig), duvelisib (Copiktra), and umbralisib (Ukoniq) have shown very good promise when combined with immunotherapies in patients with newly diagnosed or relapsed CLL/SLL.

IgHV-mutated CLL/SLL may still have benefits from CIT. Current clinical trials are investigating combining venetoclax with another TT such as ibrutinib to improve effectiveness while reducing treatment duration.  

This review concluded that targeted therapies are becoming the new standard frontline treatment for CLL/SLL.