Break Ikaros, break exhaustion

B-cell lymphoma 2 (BCL2) inhibitor venetoclax plus obinutuzumab in patients with high-risk treatment-naive CLL.The results of this study will be particularly relevant because it is expected to be enriched for patients with TP53 abnormalities, which remain an unmet medical need even in the current era.No ongoing study tests early intervention with a novelnovel combination (ie, BTKi plus BCL2 inhibitor).And, finally, should results of this study discourage genetic testing in CLL? Absolutely not!Genomic biomarkers remain prognostic and strongly contribute to the decision regarding therapy selection.In regions where chemotherapy is still used, analysis for del (17p) and other high-risk abnormalities is particularly important to avoid the high toxicity yet compromised efficacy of such treatment.In sum, the days of early intervention in CLL have not dawned upon us.Although in the era of precision oncology we continue to have increasingly safe and effective ammunition, unlike the Chekhov's gun, it is not always destined to go off. Conflict-of-interest disclosure: A.V.