642. CLL: Therapy, excluding Transplantation: Maintenance Therapy and Long-Term Follow-Up Targeted Therapy Trials
Anna Maria Fink, Jasmin Bahlo, Robrecht Sandra, Othman Al-Sawaf, et al.
Conclusion: Lenalidomide is a feasible and efficacious maintenance option for high risk CLL after chemoimmunotherapy and substantially prolonged PFS in high risk CLL patients resulting in a relative risk reduction for progression of more than 80%. An independent data monitoring committee assessed the results as being robust and reliable and recommended unblinding of the study as well as continuing treatment with lenalidomide. The PFS observed in the placebo arm independently confirms the prognostic significance of the MRD based risk assessment model, which might be used in future trials.
Robin Foà, Anna Schuh, Andrey Zaritskey, Sergey Semochkin, et al.
Conclusions: LEN maintenance therapy significantly improved PFS from 9.2 to 33.9 months following second-line treatment in pts with CLL. The incidence of invasive SPMs was similar in both arms, and LEN maintenance treatment had an expected and acceptable safety profile.
Andrew D Zelenetz, Jennifer R. Brown, Julio Delgado, Herbert Eradat, et al.
Conclusion: IDELA in combination with BR is superior to BR alone with regard to OS in RR CLL. The improvement in OS was observed across risk categories. Opportunistic infections (PJP, CMV) and SAEs were more frequent in the IDELA vs placebo arm. Results of IDELA-containing regimens may be further improved with implementation of adequate PJP prophylaxis and CMV monitoring measures. This regimen represents an important new option for pts with RR CLL.
Philip A Thompson, Paolo Strati, Michael Keating, Susan M. O'Brien, et al.
Conclusions: Among patients with CLL receiving first-line FCR, the best pre-treatment predictor of achieving MRD-negativity and subsequent longer PFS was IGHV-M. Post-treatment MRD-negativity correlated with subsequent PFS; patients with IGHV-M who achieved MRD-negativity after 3 courses had a particularly favorable outcome, even after abbreviation of therapy. However, despite achieving MRD-negativity, many patients subsequently relapse; serial MRD monitoring in peripheral blood can herald relapse with a lead-time of approximately 2 years and potentially direct monitoring and/or early intervention strategies.
Susan M. O'Brien, Richard R. Furman, Steven E. Coutre, Ian W. Flinn, et al.
Conclusions: Single-agent ibrutinib continues to show durable responses in pts with TN or R/R CLL/SLL including those with del17p, del11q, or unmutated IGVH. With extended treatment, CRs were observed in 29% of TN and 10% of R/R pts, having evolved over time. Ibrutinib provided better PFS outcomes if administered earlier in therapy than in the third-line or beyond. Those without CK experienced more favorable PFS and OS than those with CK. Ibrutinib was well tolerated with the onset of AEs decreasing over time, allowing for extended dosing for 65% of TN and 30% of R/R pts who continue treatment.
Paul M. Barr, Tadeusz Robak, Carolyn J Owen, Alessandra Tedeschi, et al.
Conclusions: With a median time on study of 28.6 mo, ibr continued to have substantial efficacy, with 88% reduction in risk of progression or death. Furthermore, the quality of responses has improved over time, with 18% of CLL/SLL pts achieving a CR/CRi with single agent ibr. Treatment limiting AEs decreased in frequency with longer follow-up, with 79% of this elderly pt population continues daily ibr. Lastly, even with a high rate of cross-over in the clb arm, OS remains significantly improved for pts randomized to ibr.