SAFETY AND EFFICACY OF THE BRUTON TYROSINE KINASE INHIBITOR IBRUTINIB IN PATIENTS WITH HAIRY CELL LEUKEMIA: INTERIM RESULTS OF A PHASE 2 STUDY
(Abstract release date: 05/21/15)
EHA Library. Jones J. 06/14/15; 103204; S790
Disclosure(s): Ohio State UniversityDivision of Hematology
Dr. Jeffrey Jones
Contributions
Contributions
Abstract
Abstract: S790
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15
Location: Room A7
Background
Effective therapy for classical hairy cell leukemia (c-HCL) refractory to purine nucleoside analog (PA) treatment is limited, and there is no accepted treatment standard for either treatment-naïve or relapsed variant hairy cell leukemia (v-HCL). Ibrutinib, an oral small molecule inhibitor of Bruton tyrosine kinase (BTK), has shown single-agent efficacy and acceptable tolerability in patients with various B-cell malignancies, including CLL, mantle cell lymphoma, and Waldenstrom macroglobulinemia. However, while BTK is expressed in HCL cells, the clinical activity of ibrutinib in this disease has not been previously assessed.
Aims
To characterize the overall response rate (complete + partial response) and safety of single-agent ibrutinib treatment for hairy cell leukemia.
Methods
This NCI/CTEP-sponsored, single-arm phase 2 study enrolled patients with c-HCL (unfit for or relapsed after PA) and v-HCL (relapsed or treatment-naïve). Eligible patients required treatment, had ECOG ≤ 2, no active infection, and preserved end-organ function. Patients received continuous oral ibrutinib (420 mg daily) in 28-day cycles. A second cohort at higher dose (840 mg daily) has been accrued after a pre-determined response endpoint was not initially met at the 420 mg dose. Response, including bone marrow biopsy with immunohistochemistry for minimal residual disease (MRD), is assessed after 8 and 12 cycles. Soluble interleukin-2 receptor levels (sIL2R) were measured serially and correlated with clinical outcome. Patients experiencing clinical benefit may continue ibrutinib indefinitely absent unacceptable toxicity or progressive disease.
Results
Data are presented for the initial 420 mg/day cohort (n = 13). Enrolled subjects (1 treatment-naïve v-HCL, 1 relapsed v-HCL, 11 relapsed c-HCL) included 12 male and 1 female patients with median age 64 years (range: 43-76) and median 4 (range: 1-11) prior therapies. All relapsed patients had received prior PA, 5 (45%) were splenectomized, and 9 (82%) had prior rituximab. The most frequent (>20%) grade 3/4 adverse events (AEs) included lymphopenia (37%), hypophosphatemia (30%), neutropenia (23%), and infection (23%). Common grade 1/2 AEs included myalgias (61%), headache (38%), dizziness (38%), diarrhea (38%), arthralgias (30%), rash (30%), and fatigue (30%). Other hematologic AEs included grade 1/2 anemia (38%) and grade 1/2 thrombocytopenia (38%). In general, response has improved with continued treatment (Table). One MRD-negative complete response (c-HCL) and 5 partial responses have been observed (ORR 46%). Four additional patients (30%) with stable disease have experienced clinical benefit not meeting criteria for PR and continue on treatment. At median follow-up of 14.5 months, 9 patients (69%) remain progression-free on treatment, 3 patients (1 v-HCL, 2 c-HCL) have progressed and 1 patient (c-HCL) discontinued in cycle 8 after failing to resolve baseline neutropenia. Redistribution lymphocytosis (peaking at day 8) occurred in both v-HCL patients and 1 c-HCL patient with circulating disease at baseline. sIL2R levels were increased at baseline in all c-HCL patients for whom data were available and normalized in responders.
Summary
Ibrutinib is well-tolerated and can induce remissions, including MRD-negative complete remission, in hairy cell leukemia patients. The correlation between sIL2R levels and response will be investigated further. Accrual continues to the second cohort.
Keyword(s): Clinical trial, Hairy cell leukemia, Kinase inhibitor
Session topic: CLL: Refining outcomes
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15
Location: Room A7
Background
Effective therapy for classical hairy cell leukemia (c-HCL) refractory to purine nucleoside analog (PA) treatment is limited, and there is no accepted treatment standard for either treatment-naïve or relapsed variant hairy cell leukemia (v-HCL). Ibrutinib, an oral small molecule inhibitor of Bruton tyrosine kinase (BTK), has shown single-agent efficacy and acceptable tolerability in patients with various B-cell malignancies, including CLL, mantle cell lymphoma, and Waldenstrom macroglobulinemia. However, while BTK is expressed in HCL cells, the clinical activity of ibrutinib in this disease has not been previously assessed.
Aims
To characterize the overall response rate (complete + partial response) and safety of single-agent ibrutinib treatment for hairy cell leukemia.
Methods
This NCI/CTEP-sponsored, single-arm phase 2 study enrolled patients with c-HCL (unfit for or relapsed after PA) and v-HCL (relapsed or treatment-naïve). Eligible patients required treatment, had ECOG ≤ 2, no active infection, and preserved end-organ function. Patients received continuous oral ibrutinib (420 mg daily) in 28-day cycles. A second cohort at higher dose (840 mg daily) has been accrued after a pre-determined response endpoint was not initially met at the 420 mg dose. Response, including bone marrow biopsy with immunohistochemistry for minimal residual disease (MRD), is assessed after 8 and 12 cycles. Soluble interleukin-2 receptor levels (sIL2R) were measured serially and correlated with clinical outcome. Patients experiencing clinical benefit may continue ibrutinib indefinitely absent unacceptable toxicity or progressive disease.
Results
Data are presented for the initial 420 mg/day cohort (n = 13). Enrolled subjects (1 treatment-naïve v-HCL, 1 relapsed v-HCL, 11 relapsed c-HCL) included 12 male and 1 female patients with median age 64 years (range: 43-76) and median 4 (range: 1-11) prior therapies. All relapsed patients had received prior PA, 5 (45%) were splenectomized, and 9 (82%) had prior rituximab. The most frequent (>20%) grade 3/4 adverse events (AEs) included lymphopenia (37%), hypophosphatemia (30%), neutropenia (23%), and infection (23%). Common grade 1/2 AEs included myalgias (61%), headache (38%), dizziness (38%), diarrhea (38%), arthralgias (30%), rash (30%), and fatigue (30%). Other hematologic AEs included grade 1/2 anemia (38%) and grade 1/2 thrombocytopenia (38%). In general, response has improved with continued treatment (Table). One MRD-negative complete response (c-HCL) and 5 partial responses have been observed (ORR 46%). Four additional patients (30%) with stable disease have experienced clinical benefit not meeting criteria for PR and continue on treatment. At median follow-up of 14.5 months, 9 patients (69%) remain progression-free on treatment, 3 patients (1 v-HCL, 2 c-HCL) have progressed and 1 patient (c-HCL) discontinued in cycle 8 after failing to resolve baseline neutropenia. Redistribution lymphocytosis (peaking at day 8) occurred in both v-HCL patients and 1 c-HCL patient with circulating disease at baseline. sIL2R levels were increased at baseline in all c-HCL patients for whom data were available and normalized in responders.
Response Category | Best Response (n = 13) | Post-Cycle 8 (n= 11) | Post-Cycle 12 (n = 11) |
CR | 1 | 0 | 1 |
PR | 5 | 5 | 5 |
SD | 6 | 6 | 4 |
PD | 1 | 0 | 1 |
Summary
Ibrutinib is well-tolerated and can induce remissions, including MRD-negative complete remission, in hairy cell leukemia patients. The correlation between sIL2R levels and response will be investigated further. Accrual continues to the second cohort.
Keyword(s): Clinical trial, Hairy cell leukemia, Kinase inhibitor
Session topic: CLL: Refining outcomes
Abstract: S790
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15
Location: Room A7
Background
Effective therapy for classical hairy cell leukemia (c-HCL) refractory to purine nucleoside analog (PA) treatment is limited, and there is no accepted treatment standard for either treatment-naïve or relapsed variant hairy cell leukemia (v-HCL). Ibrutinib, an oral small molecule inhibitor of Bruton tyrosine kinase (BTK), has shown single-agent efficacy and acceptable tolerability in patients with various B-cell malignancies, including CLL, mantle cell lymphoma, and Waldenstrom macroglobulinemia. However, while BTK is expressed in HCL cells, the clinical activity of ibrutinib in this disease has not been previously assessed.
Aims
To characterize the overall response rate (complete + partial response) and safety of single-agent ibrutinib treatment for hairy cell leukemia.
Methods
This NCI/CTEP-sponsored, single-arm phase 2 study enrolled patients with c-HCL (unfit for or relapsed after PA) and v-HCL (relapsed or treatment-naïve). Eligible patients required treatment, had ECOG ≤ 2, no active infection, and preserved end-organ function. Patients received continuous oral ibrutinib (420 mg daily) in 28-day cycles. A second cohort at higher dose (840 mg daily) has been accrued after a pre-determined response endpoint was not initially met at the 420 mg dose. Response, including bone marrow biopsy with immunohistochemistry for minimal residual disease (MRD), is assessed after 8 and 12 cycles. Soluble interleukin-2 receptor levels (sIL2R) were measured serially and correlated with clinical outcome. Patients experiencing clinical benefit may continue ibrutinib indefinitely absent unacceptable toxicity or progressive disease.
Results
Data are presented for the initial 420 mg/day cohort (n = 13). Enrolled subjects (1 treatment-naïve v-HCL, 1 relapsed v-HCL, 11 relapsed c-HCL) included 12 male and 1 female patients with median age 64 years (range: 43-76) and median 4 (range: 1-11) prior therapies. All relapsed patients had received prior PA, 5 (45%) were splenectomized, and 9 (82%) had prior rituximab. The most frequent (>20%) grade 3/4 adverse events (AEs) included lymphopenia (37%), hypophosphatemia (30%), neutropenia (23%), and infection (23%). Common grade 1/2 AEs included myalgias (61%), headache (38%), dizziness (38%), diarrhea (38%), arthralgias (30%), rash (30%), and fatigue (30%). Other hematologic AEs included grade 1/2 anemia (38%) and grade 1/2 thrombocytopenia (38%). In general, response has improved with continued treatment (Table). One MRD-negative complete response (c-HCL) and 5 partial responses have been observed (ORR 46%). Four additional patients (30%) with stable disease have experienced clinical benefit not meeting criteria for PR and continue on treatment. At median follow-up of 14.5 months, 9 patients (69%) remain progression-free on treatment, 3 patients (1 v-HCL, 2 c-HCL) have progressed and 1 patient (c-HCL) discontinued in cycle 8 after failing to resolve baseline neutropenia. Redistribution lymphocytosis (peaking at day 8) occurred in both v-HCL patients and 1 c-HCL patient with circulating disease at baseline. sIL2R levels were increased at baseline in all c-HCL patients for whom data were available and normalized in responders.
Summary
Ibrutinib is well-tolerated and can induce remissions, including MRD-negative complete remission, in hairy cell leukemia patients. The correlation between sIL2R levels and response will be investigated further. Accrual continues to the second cohort.
Keyword(s): Clinical trial, Hairy cell leukemia, Kinase inhibitor
Session topic: CLL: Refining outcomes
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 08:00 to 14.06.2015 08:15
Location: Room A7
Background
Effective therapy for classical hairy cell leukemia (c-HCL) refractory to purine nucleoside analog (PA) treatment is limited, and there is no accepted treatment standard for either treatment-naïve or relapsed variant hairy cell leukemia (v-HCL). Ibrutinib, an oral small molecule inhibitor of Bruton tyrosine kinase (BTK), has shown single-agent efficacy and acceptable tolerability in patients with various B-cell malignancies, including CLL, mantle cell lymphoma, and Waldenstrom macroglobulinemia. However, while BTK is expressed in HCL cells, the clinical activity of ibrutinib in this disease has not been previously assessed.
Aims
To characterize the overall response rate (complete + partial response) and safety of single-agent ibrutinib treatment for hairy cell leukemia.
Methods
This NCI/CTEP-sponsored, single-arm phase 2 study enrolled patients with c-HCL (unfit for or relapsed after PA) and v-HCL (relapsed or treatment-naïve). Eligible patients required treatment, had ECOG ≤ 2, no active infection, and preserved end-organ function. Patients received continuous oral ibrutinib (420 mg daily) in 28-day cycles. A second cohort at higher dose (840 mg daily) has been accrued after a pre-determined response endpoint was not initially met at the 420 mg dose. Response, including bone marrow biopsy with immunohistochemistry for minimal residual disease (MRD), is assessed after 8 and 12 cycles. Soluble interleukin-2 receptor levels (sIL2R) were measured serially and correlated with clinical outcome. Patients experiencing clinical benefit may continue ibrutinib indefinitely absent unacceptable toxicity or progressive disease.
Results
Data are presented for the initial 420 mg/day cohort (n = 13). Enrolled subjects (1 treatment-naïve v-HCL, 1 relapsed v-HCL, 11 relapsed c-HCL) included 12 male and 1 female patients with median age 64 years (range: 43-76) and median 4 (range: 1-11) prior therapies. All relapsed patients had received prior PA, 5 (45%) were splenectomized, and 9 (82%) had prior rituximab. The most frequent (>20%) grade 3/4 adverse events (AEs) included lymphopenia (37%), hypophosphatemia (30%), neutropenia (23%), and infection (23%). Common grade 1/2 AEs included myalgias (61%), headache (38%), dizziness (38%), diarrhea (38%), arthralgias (30%), rash (30%), and fatigue (30%). Other hematologic AEs included grade 1/2 anemia (38%) and grade 1/2 thrombocytopenia (38%). In general, response has improved with continued treatment (Table). One MRD-negative complete response (c-HCL) and 5 partial responses have been observed (ORR 46%). Four additional patients (30%) with stable disease have experienced clinical benefit not meeting criteria for PR and continue on treatment. At median follow-up of 14.5 months, 9 patients (69%) remain progression-free on treatment, 3 patients (1 v-HCL, 2 c-HCL) have progressed and 1 patient (c-HCL) discontinued in cycle 8 after failing to resolve baseline neutropenia. Redistribution lymphocytosis (peaking at day 8) occurred in both v-HCL patients and 1 c-HCL patient with circulating disease at baseline. sIL2R levels were increased at baseline in all c-HCL patients for whom data were available and normalized in responders.
Response Category | Best Response (n = 13) | Post-Cycle 8 (n= 11) | Post-Cycle 12 (n = 11) |
CR | 1 | 0 | 1 |
PR | 5 | 5 | 5 |
SD | 6 | 6 | 4 |
PD | 1 | 0 | 1 |
Summary
Ibrutinib is well-tolerated and can induce remissions, including MRD-negative complete remission, in hairy cell leukemia patients. The correlation between sIL2R levels and response will be investigated further. Accrual continues to the second cohort.
Keyword(s): Clinical trial, Hairy cell leukemia, Kinase inhibitor
Session topic: CLL: Refining outcomes
{{ help_message }}
{{filter}}