Ibrutinib shows promise for CLL del 17p

Single-agent ibrutinib therapy was highly effective and well tolerated in 29 patients with chronic lymphocytic leukemia and deletion of part of the short arm of chromosome 17 (del 17p) who were part of a phase II study.

Treatment with the investigational selective Bruton’s tyrosine kinase inhibitor was associated with rapid control of disease in the nodes, spleen, marrow, and blood in both treatment-naive and relapsed/refractory patients, Dr. Adrian Wiestner reported at the annual International Conference on Malignant Lymphoma in Lugano, Switzerland.

These findings are notable because patients with chronic lymphocytic leukemia (CLL) and del 17p typically have poor progression-free and overall survival when treated with standard chemoimmunotherapy, Dr. Wiestner said, adding that the potential role of ibrutinib for the treatment of these difficult-to-treat patients will be further investigated.

At a median follow-up of 9 months, 88% of 25 evaluable patients had a nodal response with a median 70% reduction in lymph node size, 48% had a partial response by International Workshop on CLL (IWCLL) criteria, and 40% had a partial response with lymphocytosis. One patient had progressive disease, said Dr. Wiestner of the National Heart, Lung, and Blood Institute, National Institutes of Health.

Of 15 treatment-naïve patients aged 33-82 years, 82% achieved a nodal response, and of 14 relapsed/refractory patients aged 56-79 years, 93% achieved a nodal response. The estimated 12-month event-free survival among the patients, who were the first in the study to reach 9-month median follow-up, was 90%, Dr. Wiestner said.

Also, 22 evaluable patients had a median 46% reduction in splenomegaly (median volume reduction of 446 mL), and tumor burden in bone marrow biopsies of 23 patients decreased by a median of 76% as assessed by immunohistochemistry for CD79a.

The percentage of tumor cells with del 17p decreased by a median of 55% in 15 patients, remained unchanged in 1 patient, and increased in 3 patients.

Treatment-naive patients included adults aged 33-82 years, and relapsed/refractory patients were adults aged 56-79 years. All were treated with 420 mg of oral ibrutinib daily until disease progression; treatment response was assessed every 6 months.

Ibrutinib, which has been granted multiple Breakthrough Therapy designations by the Food and Drug Administration – including a recent designation for the treatment of CLL or small lymphocytic lymphoma with del 17p – was well tolerated; 14% of patients experienced grade 3 or higher nonhematologic toxicities. Two deaths occurred among patients in the study, but were not deemed treatment related.

This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute.

Single-agent ibrutinib therapy was highly effective and well tolerated in 29 patients with chronic lymphocytic leukemia and deletion of part of the short arm of chromosome 17 (del 17p) who were part of a phase II study.

Treatment with the investigational selective Bruton’s tyrosine kinase inhibitor was associated with rapid control of disease in the nodes, spleen, marrow, and blood in both treatment-naive and relapsed/refractory patients, Dr. Adrian Wiestner reported at the annual International Conference on Malignant Lymphoma in Lugano, Switzerland.

These findings are notable because patients with chronic lymphocytic leukemia (CLL) and del 17p typically have poor progression-free and overall survival when treated with standard chemoimmunotherapy, Dr. Wiestner said, adding that the potential role of ibrutinib for the treatment of these difficult-to-treat patients will be further investigated.

At a median follow-up of 9 months, 88% of 25 evaluable patients had a nodal response with a median 70% reduction in lymph node size, 48% had a partial response by International Workshop on CLL (IWCLL) criteria, and 40% had a partial response with lymphocytosis. One patient had progressive disease, said Dr. Wiestner of the National Heart, Lung, and Blood Institute, National Institutes of Health.

Of 15 treatment-naïve patients aged 33-82 years, 82% achieved a nodal response, and of 14 relapsed/refractory patients aged 56-79 years, 93% achieved a nodal response. The estimated 12-month event-free survival among the patients, who were the first in the study to reach 9-month median follow-up, was 90%, Dr. Wiestner said.

Also, 22 evaluable patients had a median 46% reduction in splenomegaly (median volume reduction of 446 mL), and tumor burden in bone marrow biopsies of 23 patients decreased by a median of 76% as assessed by immunohistochemistry for CD79a.

The percentage of tumor cells with del 17p decreased by a median of 55% in 15 patients, remained unchanged in 1 patient, and increased in 3 patients.

Treatment-naive patients included adults aged 33-82 years, and relapsed/refractory patients were adults aged 56-79 years. All were treated with 420 mg of oral ibrutinib daily until disease progression; treatment response was assessed every 6 months.

Ibrutinib, which has been granted multiple Breakthrough Therapy designations by the Food and Drug Administration – including a recent designation for the treatment of CLL or small lymphocytic lymphoma with del 17p – was well tolerated; 14% of patients experienced grade 3 or higher nonhematologic toxicities. Two deaths occurred among patients in the study, but were not deemed treatment related.

This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute.

Single-agent ibrutinib therapy was highly effective and well tolerated in 29 patients with chronic lymphocytic leukemia and deletion of part of the short arm of chromosome 17 (del 17p) who were part of a phase II study.

Treatment with the investigational selective Bruton’s tyrosine kinase inhibitor was associated with rapid control of disease in the nodes, spleen, marrow, and blood in both treatment-naive and relapsed/refractory patients, Dr. Adrian Wiestner reported at the annual International Conference on Malignant Lymphoma in Lugano, Switzerland.

These findings are notable because patients with chronic lymphocytic leukemia (CLL) and del 17p typically have poor progression-free and overall survival when treated with standard chemoimmunotherapy, Dr. Wiestner said, adding that the potential role of ibrutinib for the treatment of these difficult-to-treat patients will be further investigated.

At a median follow-up of 9 months, 88% of 25 evaluable patients had a nodal response with a median 70% reduction in lymph node size, 48% had a partial response by International Workshop on CLL (IWCLL) criteria, and 40% had a partial response with lymphocytosis. One patient had progressive disease, said Dr. Wiestner of the National Heart, Lung, and Blood Institute, National Institutes of Health.

Of 15 treatment-naïve patients aged 33-82 years, 82% achieved a nodal response, and of 14 relapsed/refractory patients aged 56-79 years, 93% achieved a nodal response. The estimated 12-month event-free survival among the patients, who were the first in the study to reach 9-month median follow-up, was 90%, Dr. Wiestner said.

Also, 22 evaluable patients had a median 46% reduction in splenomegaly (median volume reduction of 446 mL), and tumor burden in bone marrow biopsies of 23 patients decreased by a median of 76% as assessed by immunohistochemistry for CD79a.

The percentage of tumor cells with del 17p decreased by a median of 55% in 15 patients, remained unchanged in 1 patient, and increased in 3 patients.

Treatment-naive patients included adults aged 33-82 years, and relapsed/refractory patients were adults aged 56-79 years. All were treated with 420 mg of oral ibrutinib daily until disease progression; treatment response was assessed every 6 months.

Ibrutinib, which has been granted multiple Breakthrough Therapy designations by the Food and Drug Administration – including a recent designation for the treatment of CLL or small lymphocytic lymphoma with del 17p – was well tolerated; 14% of patients experienced grade 3 or higher nonhematologic toxicities. Two deaths occurred among patients in the study, but were not deemed treatment related.

This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute.