The SAKK 34/17 trial evaluated the efficacy of a modified treatment schedule with ibrutinib and venetoclax (IV) in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). This combination targets the dual pathophysiology of CLL by inhibiting both B-cell receptor signaling and BCL2-mediated survival. IV therapy typically begins with a brief ibrutinib lead-in phase to reduce tumor burden and mitigate the risk of tumor lysis syndrome (TLS). However, despite a significant reduction in lymph node and spleen size within three months, lymphocyte counts may remain elevated, a known risk factor for TLS.

To address this, the SAKK 34/17 phase II study extended the ibrutinib lead-in phase to six months for improved tumor control and prolonged the venetoclax combination phase to at least 24 months to optimize response, enhancing both complete remission rates and the transition to a low-risk TLS category.

The findings of this study suggest that the modified IV schedule offers an acceptable benefit-risk profile for patients with R/R CLL, providing an advantage over continuous BTKi therapy, with no evidence of emerging resistance clones.

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