Interpretation and Clinical Implications of SEQUOIA Arm C Results in CLL/SLL

This discussion builds on the results of the SEQUOIA trial, emphasizing its importance as the largest prospective dataset for patients with deletion 17p in the frontline treatment of CLL. The findings showed that patients with TP53 abnormalities achieved outcomes comparable to those without such mutations, particularly in terms of PFS and complete response (CR) rates. Specifically, the PFS in the deletion 17p cohort was around 72%, closely mirroring the outcomes in the wild-type group. This similarity in outcomes challenges the historical assumption that deletion 17p inevitably leads to poor response and supports the efficacy of BTK inhibitor monotherapy in overcoming this high-risk genetic marker.

The conversation further compares this approach with other treatment strategies. For example, time-limited therapy options, such as those studied in trials such as CLL14 and Clover, tend to show lower PFS rates for patients with deletion 17p —around 40% at 5 years. These comparisons highlight the strength of the SEQUOIA data and the potential of BTK inhibitors, particularly second-generation agents, to offer durable responses. The speakers strongly advocate for using newer BTK inhibitors over ibrutinib, citing both efficacy and safety concerns, including reduced cardiac risk. They also note that adding anti-CD20 antibodies (eg, obinutuzumab) offers no added benefit in patients with deletion 17p, reinforcing monotherapy as the standard.

The key takeaways include the ability of BTK monotherapy to neutralize the adverse prognostic value of deletion 17p in the short to medium term, the consistency of CR and PFS rates across subgroups, and the reassurance this offers patients. This is especially valuable for individuals who may feel discouraged after learning about their high-risk mutation. Overall, the data provide confidence that deletion 17p is no longer a barrier to effective frontline therapy when the right agents are used. Continued long-term follow-up will be important to assess durability and late-emerging safety concerns.