Abstract Background: The H. Jean Khoury Cure CML Consortium (HJKC3) was established with the overarching goals of improving the outcomes for patients (pts) with CML and achieving a deeper understanding of CML biology through innovative clinical trial paired with rationally-designed correlative studies within a well-coordinated network of CML Centers of Excellence. The HJKC3 CML registry collects data from patients treated at participating HJKC3 institutions. This study used data from the CML registry to describe the demographic and clinical characteristics of pts treated with TKIs in real-world settings across the US. Secondary objectives included assessing clinical outcomes, adverse events, PROs, and reasons for treatment modifications. Methods: Data from deceased pts are collected under a waiver of informed consent; living pts provide informed consent. Pts are registered, and retrospective data from the electronic health record are entered into a REDCap database by trained data managers. Prospective data are collected approximately every 6 months. Pts have the option to complete annual patient-reported outcome (PRO) assessments via REDCap. NIH PROMIS measures are administered; a score of 50 corresponds to the average score in the U.S. general population, and a score at least 1 standard deviation (10 points) worse than average is considered moderate-to-severe. Inclusion criteria for data extraction for this study included pts diagnosed with chronic phase CML on or after June 1st 2010 and treated with imatinib (IM), dasatinib (DAS), nilotinib (NIL), bosutinib (BOS), ponatinib (PON), or asciminib (ASC). Pts who were on a clinical trial at any time during their TKI therapy were excluded. Summary statistics are presented. Results: Of the 342 pts in the registry, 208 were eligible for this study, and 115 completed a PRO assessment at registration (55%). The median age was 51 years (range 38-62), 52% were male, and race was white (80%), Black (12.5%), Asian (3.5%), andother/unknown (4%). At the time of entering the registry, 15% were deceased. First-line TKI was IM (43%), DAS (41%), NIL (12%), BOS (2.9%), and ASC (1.4%). Current TKI was IM (14%), DAS (43%), NIL (6.3%), BOS (12%), PON (9.7%), and ASC (15%). Overall, 34.6% of pts had received one TKI, 29.8% received two, 18.2% received three, and 17% received three TKIs. Among the 37 patients treated with asciminib, 3 received it as first-line therapy, 6 as second-line, and 28 as third-line or later.The percentage of pts who discontinued their first TKI for any reason was IM (74%), DAS (52%), NIL (38%), and BOS (83%). Discontinuation of first-line TKI for intolerance vs resistance was 31% vs. 43% for IM, 32% vs 20% for DAS, 38% vs 0% for NIL, and 17% vs 67% for BOS. Currently, most pts are not on full dose TKI: IM 38% were on 400 mg/day, DAS 71.1% were 100 mg/day, NIL 84% were on 600 mg /day, BOS 71% 400 mg/day, PON 55% 30 mg/day, and ASC 34.3% 80 mg/day. GI toxicities (nausea, vomiting and diarrhea) were reported in 65% (IM), 64% (BOS), 29% (DAS), 26.1% (NIL), 25.1% (PON) and 16.2% (ASC). Pleural effusions were reported in 13% (DAS), 4% (BOS), 2.7 % (ASC), with none for IM, NIL, PON. Cytopenias occurred in 19% (PON), 18% (NIL), 17% (DAS), 17% (IM), 8% (BOS), 5.4% (ASC), and fatigue was reported in 29% (DAS), 28% (IM), 22% (ASC), 16% (NIL), 16% (PON) and 14% (BOS). Cardiovascular symptoms were reported in 13% (PON), 11% (NIL), 2.8% (DAS), 2.7% (ASC), 2.5% (IM), 2.6% and none for BOS. Participants who completed a PRO assessment reported on their symptoms and functioning over the preceding week. At registration, 27% reported moderate-to-severe pain that interfered with daily life, 24% had moderate-to-severe physical dysfunction, 19% had moderate-to-severe cognitive dysfunction, 18% reported moderate-to-severe anxiety, 14% reported moderate-to-severe nausea, and 10% reported moderate-to-severe diarrhea. Conclusion: The HJKC3 registry data suggests that currently the most common first-line TKIs prescribed in the US are IM and DAS. More than 60% of CML pts receive more than one TKI over time. In addition, most pts in the US are taking doses lower than the labeled starting doses. Despite this, a sizeable number of pts report ongoing moderate-to-severe symptoms and dysfunction. The adverse events recorded in clinical notes track with published phase 2 and 3 studies. Taken together, these results add to ongoing efforts to clarify the long-term effects of TKIs at a population level.
Rein et al. (Mon,) studied this question.