TY - JOUR
T1 - Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia
T2 - Extended phase 3 results from RESONATE-2
AU - Barr, Paul M.
AU - Robak, Tadeusz
AU - Owen, Carolyn
AU - Tedeschi, Alessandra
AU - Bairey, Osnat
AU - Bartlett, Nancy L.
AU - Burger, Jan A.
AU - Hillmen, Peter
AU - Coutre, Steven
AU - Devereux, Stephen
AU - Grosicki, Sebastian
AU - McCarthy, Helen
AU - Li, Jianyong
AU - Simpson, David
AU - Offner, Fritz
AU - Moreno, Carol
AU - Zhou, Cathy
AU - Styles, Lori
AU - James, Danelle
AU - Kipps, Thomas J.
AU - Ghia, Paolo
N1 - Funding Information:
This study was supported by Pharmacyclics LLC, an AbbVie company, by grants (CA016672 and 5P01CA081534-14) from the National Institutes of Health, and by the MD Anderson Moon Shot Program in CLL. Pharmacyclics LLC, an AbbVie company, sponsored and designed the study. Study investigators and their research teams collected the data. The sponsor confirmed data accuracy and performed analysis of the data. Medical writing support was funded by the sponsor.
Publisher Copyright:
©2018 Ferrata Storti Foundation.
PY - 2018/8/31
Y1 - 2018/8/31
N2 - Results of RESONATE-2 (PCYC-1115/1116) supported approval of ibrutinib for first-line treatment of chronic lymphocytic Rleukemia. Extended analysis of RESONATE-2 was conducted to determine long-term efficacy and safety of ibrutinib in older patients with chronic lymphocytic leukemia. A total of 269 patients aged ≥65 years with previously untreated chronic lymphocytic leukemia without del(17p) were randomized 1:1 to ibrutinib (n=136) or chlorambucil (n=133) on days 1 and 15 of a 28-day cycle for 12 cycles. Median ibrutinib treatment duration was 28.5 months. Ibrutinib significantly prolonged progression-free survival versus chlorambucil (median, not reached vs. 15 months; hazard ratio, 0.12; 95% confidence interval, 0.07-0.20; P<0.0001). The 24-month progression-free survival was 89% with ibrutinib (97% and 89% in patients with del[11q] and unmutated immunoglobulin heavy chain variable region gene, respectively). Progression-free survival rates at 24 months were also similar regardless of age (<75 years [88%], ≥75 years [89%]). Overall response rate was 92% (125/136). Rate of complete response increased substantially from 7% at 12 months to 18% with extended follow up. Greater quality of life improvements occurred with ibrutinib versus chlorambucil in Functional Assessment of Chronic Illness Therapy-Fatigue (P=0.0013). The most frequent grade ≥3 adverse events were neutropenia (12%), anemia (7%), and hypertension (5%). Rate of discontinuations due to adverse events was 12%. Results demonstrated that first-line ibrutinib for elderly patients with chronic lymphocytic leukemia provides sustained response and progression-free survival benefits over chemotherapy, with depth of response improving over time without new toxicity concerns. This trial was registered at clinicaltrials.gov identifier 01722487 and 01724346.
AB - Results of RESONATE-2 (PCYC-1115/1116) supported approval of ibrutinib for first-line treatment of chronic lymphocytic Rleukemia. Extended analysis of RESONATE-2 was conducted to determine long-term efficacy and safety of ibrutinib in older patients with chronic lymphocytic leukemia. A total of 269 patients aged ≥65 years with previously untreated chronic lymphocytic leukemia without del(17p) were randomized 1:1 to ibrutinib (n=136) or chlorambucil (n=133) on days 1 and 15 of a 28-day cycle for 12 cycles. Median ibrutinib treatment duration was 28.5 months. Ibrutinib significantly prolonged progression-free survival versus chlorambucil (median, not reached vs. 15 months; hazard ratio, 0.12; 95% confidence interval, 0.07-0.20; P<0.0001). The 24-month progression-free survival was 89% with ibrutinib (97% and 89% in patients with del[11q] and unmutated immunoglobulin heavy chain variable region gene, respectively). Progression-free survival rates at 24 months were also similar regardless of age (<75 years [88%], ≥75 years [89%]). Overall response rate was 92% (125/136). Rate of complete response increased substantially from 7% at 12 months to 18% with extended follow up. Greater quality of life improvements occurred with ibrutinib versus chlorambucil in Functional Assessment of Chronic Illness Therapy-Fatigue (P=0.0013). The most frequent grade ≥3 adverse events were neutropenia (12%), anemia (7%), and hypertension (5%). Rate of discontinuations due to adverse events was 12%. Results demonstrated that first-line ibrutinib for elderly patients with chronic lymphocytic leukemia provides sustained response and progression-free survival benefits over chemotherapy, with depth of response improving over time without new toxicity concerns. This trial was registered at clinicaltrials.gov identifier 01722487 and 01724346.
UR - http://www.scopus.com/inward/record.url?scp=85052879292&partnerID=8YFLogxK
U2 - 10.3324/haematol.2018.192328
DO - 10.3324/haematol.2018.192328
M3 - Article
C2 - 29880603
AN - SCOPUS:85052879292
SN - 0390-6078
VL - 103
SP - 1502
EP - 1510
JO - Haematologica
JF - Haematologica
IS - 9
ER -