Outcomes of BTKi therapy for CLL after progression on venetoclax (VEN). (A) Individual patient characteristics and timelines of outcomes and treatments after BTKi initiation. Arrows at the ends of lanes indicate ongoing response to treatment at last follow-up, circles indicate death, and other treatments have specific symbols as indicated. The columns on the left indicate relevant pre-BTKi features. Gray fill indicates presence of a variable; white fill indicates absence. Where a TP53 abnormality or CK was first detected after progression on VEN, the cells have a diagonal line. In all other cases, the CLL patient had these genetic features before treatment with VEN. Patients who were treated for RT before BTKi are denoted by a red fill. Ibrutinib was the BTKi used in all patients except where zanubrutinib (ZANU) is indicated. Histology, treatment, and response of RT were as follows: lanes 1 and 5: diffuse large B-cell lymphoma (DLBCL): rituximab, ifosfamide, carboplatin, and etoposide followed by autologous (auto) SCT (CR in both cases); lane 6: DLBCL: rituximab, methotrexate, vincristine, and procarbazine followed by radiotherapy (partial remission [PR]); lane 13: Hodgkin variant: doxorubicin, bleomycin, vinblastine, and dacarbazine (CR); and lane 14: Hodgkin variant: cyclophosphamide, doxorubicin, etoposide, and prednisolone followed by radiotherapy (CR). (B) PFS (blue) and overall survival (OS) on BTKi (red) from initiation of BTKi after disease progression on VEN. In both, patient data were censored at allogeneic (allo) SCT if this occurred in first response to BTKi. (C) PFS on BTKi stratified by prior remission to VEN ≥24 (blue) or <24 months (red). HR, hazard ratio; UNK, unknown.