642. CLL: Therapy, excluding Transplantation: BTK Inhibitors and CAR T Cells in CLL
Conclusion cited from the abstract: In this study, we have completed enrollment of one of the largest prospective cohorts of TN patients with del(17p) CLL/SLL. Preliminary results suggested that zanubrutinib was active and generally well tolerated. Clinical trial information: NCT03336333.
Constantine S. Tam, et al.
Conclusion cited from the abstract: These data suggest that zanubrutinib monotherapy was generally well tolerated and active in the treatment of patients with CLL/SLL irrespective of 17p deletion status. The ORR, CRR, and 2-year PFS rates suggest this next generation BTK inhibitor can achieve deep and durable responses in patients with CLL/SLL.
Conclusion cited from the abstract: Phase 1 data with LOXO-305 demonstrate a favorable safety profile and provide proof-of-concept evidence of efficacy in heavily pretreated CLL and MCL patients, including patients with acquired resistance to available BTKis and venetoclax.
Anthony R. Mato, et al.
Conclusion cited from the abstract: In the largest experience of therapies following VEN dc in CLL, we demonstrated that therapy selection following VEN requires consideration of prior novel agent exposure and reasons for discontinuation. For BTKi naïve pts, selection of a covalently binding BTKi results in high ORR and durable remissions. PFS-2 data provide reassurance for using VEN prior to IBR. For BTKi exposed pts, BTK inhibition is not effective in the setting of BTKi resistance but should be considered if prior BTKi intolerance. PI3K inhibition following VEN does not appear to result in durable remissions even in PI3Ki naïve pts, suggesting possible overlap in resistance mechanisms (BTK or VEN with PI3K). We conclude that BTKi in naïve or previously responsive pts and alloHSCT following VEN appear to be the most effective strategies with durable responses. These data suggest that a number of effective regimens exist for post VEN pts, providing support for VEN use earlier in the course of CLL.
Tanya Siddiqi, et al.
Conclusion cited from the abstract: In this population of heavily pretreated pts with R/R CLL/SLL (all received prior ibrutinib and half failed both prior venetoclax and ibrutinib), liso-cel toxicities, including CRS and NE, were manageable at both DLs tested. Objective responses, CRs, and uMRD were rapidly achieved, with durable responses past 6 months. Updated safety, pharmacokinetic, and efficacy results from the phase 1 monotherapy part of the study will be reported. The phase 2 portion of the study is currently enrolling at DL2.
Jennifer Woyach, et al.
Conclusion cited from the abstract: Here we show for the first time that CLL relapse on A is mediated predominantly by mutations in BTK similar to I. While not unexpected, this is significant as resistant patterns could be different given the more selective nature of A as well as potentially higher BTK occupancy over time due to twice daily dosing. Monitoring for BTK resistance offers the opportunity to intervene clinically before symptomatic disease.