RESONATE-2 update: First-line ibrutinib has sustained efficacy in older CLL patients

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.

In older patients with chronic lymphocytic leukemia (CLL), first-line treatment with ibrutinib resulted in a long-term progression-free survival benefit versus chemotherapy, according to extended follow-up results of a phase 3 trial.

The quality of response to ibrutinib continued to improve over time in the study, including a substantial increase in the proportion of patients achieving complete response, the updated results of the RESONATE-2 trial show.

Rates of serious adverse events decreased over time in the study, while common reasons for initiating treatment, such as marrow failure and disease symptoms, all improved to a greater extent than with chlorambucil, reported Paul M. Barr, MD, of the University of Rochester (N.Y.) and colleagues.

“These data support the use of ibrutinib in the first-line treatment of CLL as a chemotherapy-free option that can be taken continuously, achieving long-term disease control for the majority of patients, including those with high-risk features,” Dr. Barr and coauthors said in the journal Haematologica.

Previously reported primary results of the RESONATE-2 trial, which showed an 84% reduction in risk of death for ibrutinib versus chlorambucil with a median follow-up of 18 months, led to the approval of ibrutinib for first-line CLL treatment, the authors said.

The study included 269 patients with untreated CLL or small lymphocytic lymphoma who had active disease and were at least 65 years of age. They were randomized 1:1 to ibrutinib or chlorambucil.

Out of 136 ibrutinib-treated patients, 107 (79%) remained on therapy at this extended analysis, which had a median follow-up of 29 months.

The extended analysis also showed an 88% reduction in risk of progression or death for those patients randomized to ibrutinib (P less than .0001), with significant improvements in subgroups evaluated, which include groups typically considered high risk, according to Dr. Barr and colleagues.

The rate of complete response improved over time in ibrutinib-treated patients, from 7% at 12 months, to 15% at 24 months, and to 18% with a maximum of 36 months’ follow-up, they said.

The overall response rate for ibrutinib was 92% in this extended analysis, with comparable findings in high-risk subgroups, including those with del(11q) at 100% and unmutated IGHV at 95%, according to the report.

Lymphadenopathy improved in most ibrutinib-treated patients, with complete resolution in 42% versus 7% with chlorambucil. Splenomegaly improved by at least 50% in 95% of ibrutinib-treated patients versus 52% for chlorambucil, with complete resolution in 56% of ibrutinib-treated patients and 22% of chlorambucil-treated patients.

Adverse events of grade 3 or greater were generally seen more often in the first year of ibrutinib therapy and decreased over time. Rates of grade 3 or greater neutropenia, anemia, and thrombocytopenia were 8.1%, 5.9%, and 2.2%, respectively, in the first 12 months of treatment; those decreased to 0%, 1%, and 0% in the third year.

The rate of atrial fibrillation increased from 6% in the primary analysis to 10% in extended follow-up; however, investigators said ibrutinib dose reductions and discontinuations because of this adverse effect were uncommon and less frequent with extended treatment.

“Atrial fibrillation therefore appears manageable and does not frequently necessitate ibrutinib discontinuation,” they concluded.

The study was supported by Pharmacyclics, an AbbVie company, and by grants from the National Institutes of Health and the MD Anderson Moon Shot Program in CLL. Pharmacyclics designed the study and performed analysis of the data. Several study authors reported funding from various companies, including Pharmacyclics.

SOURCE: Barr PM, et al. Haematologica. 2018;103(9):1502-10.