Study Warns on Venetoclax in Double-Hit Lymphoma

Adding the BCL2 inhibitor venetoclax to chemoimmunotherapy worsened outcomes and caused excess mortality in patients with newly diagnosed double-hit lymphoma in a randomized phase II trial. The negative safety signal challenges the rationale of combining venetoclax with standard regimens in this aggressive B-cell non-Hodgkin lymphoma subtype characterized by concurrent MYC and BCL2 rearrangements. These results suggest that despite the biological logic of targeting BCL2 in tumors harboring BCL2 translocations, the added toxicity outweighs any potential benefit in this setting.