Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study

TY - JOUR

T1 - Depth and durability of response to ibrutinib in CLL

T2 - 5-year follow-up of a phase 2 study

AU - Ahn, Inhye E

AU - Farooqui, Mohammed Z H

AU - Tian, Xin

AU - Valdez, Janet

AU - Sun, Clare

AU - Soto, Susan

AU - Lotter, Jennifer

AU - Housel, Stephanie

AU - Stetler-Stevenson, Maryalice

AU - Yuan, Constance M

AU - Maric, Irina

AU - Calvo, Katherine R

AU - Nierman, Pia

AU - Hughes, Thomas E

AU - Saba, Nakhle S

AU - Marti, Gerald E

AU - Pittaluga, Stefania

AU - Herman, Sarah E M

AU - Niemann, Carsten U

AU - Pedersen, Lone B

AU - Geisler, Christian H

AU - Childs, Richard

AU - Aue, Georg

AU - Wiestner, Adrian

N1 - © 2018 by The American Society of Hematology.

PY - 2018/5/24

Y1 - 2018/5/24

N2 - The safety and efficacy of ibrutinib (420 mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase 2 study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled because of age 65 years or older (elderly cohort). Both cohorts included patients with treatment-naive (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20.9%) patients for a rate of 6.4 per 100 patient-years. No serious bleeding occurred. The overall response rate at 6 months, the primary study endpoint, was 95.8% for the TP53 cohort (95% confidence interval, 85.7%-99.5%) and 93.9% for the elderly cohort (95% confidence interval, 79.8%-99.3%). Depth of response improved with time: at best response, 14 (29.2%) of 48 patients in the TP53 cohort and 9 (27.3%) of 33 in the elderly cohort achieved a complete response. Median minimal residual disease (MRD) in peripheral blood was 3.8 3 102 2 at 4 years, with MRD-negative (<102 4 ) remissions in 5 (10.2%) patients. In the TP53 cohort, the estimated 5-year progression-free survival (PFS) was 74.4% in TN-CLL compared with 19.4% in RR-CLL (P 5 .0002), and overall survival (OS) was 85.3% vs 53.7%, respectively (P 5 .023). In the elderly cohort, the estimated 5-year PFS and OS in RR-CLL were 64.8% and 71.6%, respectively, and no event occurred in TN-CLL. Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733.

AB - The safety and efficacy of ibrutinib (420 mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase 2 study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled because of age 65 years or older (elderly cohort). Both cohorts included patients with treatment-naive (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20.9%) patients for a rate of 6.4 per 100 patient-years. No serious bleeding occurred. The overall response rate at 6 months, the primary study endpoint, was 95.8% for the TP53 cohort (95% confidence interval, 85.7%-99.5%) and 93.9% for the elderly cohort (95% confidence interval, 79.8%-99.3%). Depth of response improved with time: at best response, 14 (29.2%) of 48 patients in the TP53 cohort and 9 (27.3%) of 33 in the elderly cohort achieved a complete response. Median minimal residual disease (MRD) in peripheral blood was 3.8 3 102 2 at 4 years, with MRD-negative (<102 4 ) remissions in 5 (10.2%) patients. In the TP53 cohort, the estimated 5-year progression-free survival (PFS) was 74.4% in TN-CLL compared with 19.4% in RR-CLL (P 5 .0002), and overall survival (OS) was 85.3% vs 53.7%, respectively (P 5 .023). In the elderly cohort, the estimated 5-year PFS and OS in RR-CLL were 64.8% and 71.6%, respectively, and no event occurred in TN-CLL. Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents/administration & dosage

KW - Bone Marrow/metabolism

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Kaplan-Meier Estimate

KW - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Neoplasm, Residual

KW - Protein Kinase Inhibitors/administration & dosage

KW - Pyrazoles/administration & dosage

KW - Pyrimidines/administration & dosage

KW - Treatment Outcome

U2 - 10.1182/blood-2017-12-820910

DO - 10.1182/blood-2017-12-820910

M3 - Journal article

C2 - 29483101

SN - 0006-4971

VL - 131

SP - 2357

EP - 2366

JO - Blood

JF - Blood

IS - 21

ER -