Background: CLL is the most common type of leukemia in adults in the US. Traditionally, chemotherapy (CT) and chemoimmunotherapy (CIT) have been the treatment mainstay, with new oral-targeted options recently becoming available. CLL patients (pts) who relapse and/or are refractory to their initial treatment have poorer outcomes compared with pts who are treatment naive, especially if they harbor high-risk genetic features (eg, 17p deletion [del(17p)]). As oral-targeted therapies became available in the US for pts with CLL, including those positive for del(17p), treatment patterns have changed. However, questions about how to sequence new therapies and traditional CIT/immunotherapy (IT) remain.
Aims: This study used an electronic health record database to characterize treatment sequencing and associated outcomes in relapsed/refractory (R/R) CLL pts. The association between treatment choices and outcomes stratified by del(17p) status and previous line of therapy (LoT) was also explored.
Methods: This was a retrospective observational study in CLL utilizing a large, longitudinal, demographically and geographically diverse database of US cancer pts (Flatiron Health 06/2017). An analytic cohort of pts treated mostly at community practice sites who initiated a LoT after Jan 2014 was developed. Time to next LoT or death (TTNLD), defined as the start date of a LoT to the start date of next LoT or death or the date of data cut, whichever comes first, was analyzed by Kaplan-Meier method. A Cox proportional hazard model was used for unadjusted and adjusted analyses including hazard ratios (HR) estimation.
Results: The analytic cohorts included 1,457 and 613 pts who initiated 2nd and 3rd LoT with either B-cell receptor or B-cell lymphoma 2 (BCR/BCL2) inhibitor or CT/CIT/IT after Jan 2014. Average age at CLL diagnosis was 64.8 years (64.0 years); 61.6% (60.7%) of pts were male; and 72.2% (71.8%) were Caucasian (2nd LoT, 3rd LoT, respectively). A subcohort included 374 pts who received either BCR/BCL2 or CT/CIT/IT as 2nd LoT following initial CT/CIT/IT. Among these 374 pts, 161 (43.0%) were treated with a BCR/BCL2 inhibitor; 213 (57.0%) were treated with CT/CIT/IT for the 2nd LoT. The rate of del(17p)-specific testing before initiation of 2nd LoT was 67.1%, and 68.4% before the initiation of 3rd LoT.
Median TTNLD in del(17p)-negative pts who initiated 2nd LoT with a BCR/BCL2 inhibitor was not reached (proportion of pts who experienced TTNLD at 06/2017 was less than 50%; Figure 1) vs 21.5 months in pts who initiated 2nd LoT with CT/CIT/IT; similarly, for del(17p)-positive pts: 28.3 months with BCR/BCL2 inhibitors vs 9.8 months for CT/CIT/IT. Pts treated with a BCR/BCL2 inhibitor had a lower risk of advancing to subsequent LoT than pts treated with CT/CIT/IT (HR 0.56; 95% CI: 0.47-0.67 [Figure 1, Table]).
Median TTNLD in del(17p)-negative pts who initiated 3rd LoT with a BCR/BCL2 inhibitor was 31.6 vs 12.2 months in pts who initiated 3rd LoT with CT/CIT/IT; similarly, for del(17p)-positive pts: 12.6 months with BCR/BCL2 inhibitors vs 5.5 months for CT/CIT/IT. The HR for advancing from 3rd LoT to subsequent LoT was 0.46 (95% CI: 0.36-0.58) for pts treated with a BCR/BCL2 inhibitor compared with CT/CIT/IT (Figure 2, Table).
Pts who were treated with 2nd-line BCR/BCL2 inhibitor following CT/CIT/IT had a median TTNLD that was not reached, significantly longer than the median TTNLD in pts who had CT/CIT/IT after initial CT/CIT/IT (median 26.6 months; HR 0.52; 95% CI: 0.35-0.78).
Conclusion: In this real-world analysis of treatment pattern of CLL pts, regardless of del(17p) status or LoT (2nd or 3rd), R/R CLL pts receiving an oral-targeted therapy had a longer TTNLD compared with pts receiving CT/CIT/IT. In particular, pts receiving a BCR/BCL2 inhibitor as subsequent LoT to initial treatment with CT/CIT/IT had a longer TTNLD than pts receiving CT/CIT/IT following CT/CIT/IT.
Kapustyan: AbbVie Inc.: Employment, Equity Ownership. Keim: AbbVie Inc.: Employment, Equity Ownership, Other: I am an employee of AbbVie, Inc and may own AbbVie and/or Abbott stock. Meissner: AbbVie Inc.: Employment, Equity Ownership, Other: I am an employee of AbbVie, Inc and may own AbbVie and/or Abbott stock. Nielsen: AbbVie Inc.: Employment, Equity Ownership. Zhang: AbbVie Inc.: Employment, Equity Ownership. Jiang: AbbVie Inc.: Employment, Equity Ownership.
Asterisk with author names denotes non-ASH members.