Type: Oral
Session: 642. CLL: Therapy, excluding Transplantation II
Hematology Disease Topics & Pathways:
Elderly, B-Cell Lymphoma
Methods: From Oct 2015 to June 2019, informCLL (PCYC-1134; NCT02582879) enrolled eligible pts with CLL/SLL who were ≥18 years (y), initiated FDA-approved treatment for CLL/SLL within ±45 days of enrollment and provided consent. Pts were classified into 5 groups based on treatment received at enrollment (index): ibrutinib (single agent or combination), chemoimmunotherapy (CIT), chemotherapy (CT), immunotherapy (IT), and other novel agents. Descriptive analyses are presented.
Results: The registry fully enrolled with 1461 pts: 855 (59%) previously untreated and 606 (41%) relapsed/refractory (R/R) pts. Community-based practices enrolled 93% of pts. The median age was 71 y (33% ≥75 y), the majority were male (64%), and 88% had ECOG performance status of 0/1. For pts with staging performed at enrollment (n=852), 51% had Rai stage III/IV. Median (range) time from diagnosis to initial treatment on study was 18.6 months (mos, <0.1−471.3) for previously untreated pts; median time from diagnosis to index treatment was 84.27 mos (1.1−469.4) for R/R pts. Median (range) follow-up for previously untreated pts was 14.9 mos (0.03−46.9) and was 15.3 mos (0.03−44.0) for R/R pts.
FISH testing was performed in 28% (n=415) of pts and was more frequent in previously untreated vs R/R pts (33% vs 21%). TP53 mutation testing was performed in 11% (n=162) of pts (previously untreated: 13%; R/R: 9%). IGHV mutational status testing was performed in 12% (n=171) of pts (previously untreated: 13%; R/R 10%). Of pts with prognostic biomarker testing, 24% (100/415) had del(17p), 27% (43/162) had TP53 mutation, and 71% (121/171) had unmutated IGHV. Prognostic biomarker testing by treatment group is shown in Figure 1.
Table 1 shows the distribution of pts receiving different treatments on study. Across lines of therapy, the most common treatment was ibrutinib (46%); the majority (87%) started ibrutinib treatment at the recommended daily dose of 420 mg, and pts continuing ibrutinib therapy largely did not require dose modifications (75%). At 12 or 24 mos, 77% (307/401) and 68% (126/184) of pts continued on ibrutinib treatment, respectively. For pts who completed the most common CIT regimens (bendamustine + rituximab [BR] and fludarabine + cyclophosphamide + rituximab), 80% and 85%, respectively, received <6 cycles per physician discretion. Only 6% (n=82) of pts were treated with other novel agents as index treatment; venetoclax (single agent or combination) was the most commonly administered other novel agent, primarily used in R/R (n=56) pts vs previously untreated pts (n=1). Treatment for pts with high-risk features was examined for all pts. Of 100 pts with del(17p), 59% received ibrutinib, 28% CIT, 7% IT, and 6% other novel agents. Of 43 pts with TP53 mutation, 67% received ibrutinib, 21% CIT/CT, 5% IT, and 7% other novel agents. The proportion of pts with del(17p) and/or TP53 mutation receiving CIT decreased over time (2016–2018), although sample size was small. Of 121 pts with unmutated IGHV, 49% received ibrutinib, 39% CIT/CT, 7% IT, and 5% other novel agents.
Conclusions: The informCLL registry provides an opportunity to prospectively assess CLL treatment patterns in the era of novel agents. The most common index treatment was ibrutinib and the majority of ibrutinib-treated pts remained on therapy at 2 y follow-up; CIT (primarily BR) was also used for one-third of patients. Prognostic biomarker testing rates were poor, especially for TP53 and IGHV mutational status. Data from informCLL also indicate a ‘knowledge gap’ in terms of prognostic marker testing and selection of therapies for pts with high-risk disease. Data from the now complete pt population and with continued follow up will allow for the ongoing evaluation of real-world treatment decisions and pt care that cannot be addressed by data from randomized clinical trials.
Disclosures: Mato: Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; BeiGene: Consultancy; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genentech: Consultancy, Research Funding; LOXO: Consultancy, Research Funding. Barrientos: Janssen: Honoraria; Oncternal Therapeutics: Research Funding; Sandoz: Consultancy; Gilead: Consultancy; Genentech: Consultancy; Bayer: Consultancy; AstraZeneca: Consultancy. Sharman: AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BeiGene: Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding. Brander: Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; MEI Pharma: Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; Teva: Consultancy, Honoraria; Novartis: Consultancy, Other; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Tolero: Research Funding; Tolero: Research Funding; Teva: Consultancy, Honoraria; NCCN: Other; Juno/Celgene/BMS: Other, Research Funding; Genentech: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Other; NCCN: Other; Verastem: Consultancy, Honoraria, Other, Research Funding. Kadish: Bluebird Bio: Current equity holder in publicly-traded company; Blueprint Medicines: Current equity holder in publicly-traded company; Teva Pharmaceutical: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current equity holder in publicly-traded company; Editas Medicine: Current equity holder in publicly-traded company; Johnson & Johnson: Current equity holder in publicly-traded company; Sarepta Therapeutics: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company; Agios: Current equity holder in publicly-traded company; Celgene: Current equity holder in publicly-traded company, Speakers Bureau; Takeda: Speakers Bureau. Arango-Hisijara: Bristol-Myers Squibb: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Upasani: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment; Protagonist Therapeutics: Current Employment. Han: Johnson and Johnson: Current equity holder in publicly-traded company; Janssen: Current Employment, Other: Travel expenses. Huang: Janssen Scientific Affairs, LLC: Current Employment; Johnson & Johnson: Current equity holder in publicly-traded company. Iyengar: Express Scripts: Patents & Royalties; AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Ghosh: Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Celgene/Bristol-Myers Squibb: Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding.