Faculty Collaboration Database

Outcomes of front-line ibrutinib treated CLL patients excluded from landmark clinical trial. Am J Hematol 2018 Nov;93(11):1394-1401

Date

08/23/2018

Pubmed ID

30132965

Pubmed Central ID

PMC7552812

DOI

10.1002/ajh.25261

Scopus ID

2-s2.0-85053839727 (requires institutional sign-in at Scopus site)   54 Citations

Abstract

Ibrutinib demonstrated superior response rates and survival for treatment-naïve chronic lymphocytic leukemia (CLL) patients in a pivotal study that excluded patients younger than 65 (<65) and/or with chromosome 17p13 deletion (del[17p13]). We examined outcomes and toxicities of CLL patients who would have been excluded from the pivotal study, specifically <65 and/or those with del[17p13]. This multicenter, retrospective cohort study examined CLL patients treated with front-line ibrutinib at 20 community and academic centers, categorizing them based on key inclusion criteria for the RESONATE-2 trial: <65 vs ≥65 and present vs absent del[17p13]. Of 391 included patients, 57% would have been excluded from the pivotal study. Forty-one percent of our cohort was <65, and 30% had del(17p13). Patients <65 were more likely to start 420 mg of ibrutinib daily; those who started at reduced doses had inferior PFS. The most common adverse events were arthralgias, fatigue, rash, bruising, and diarrhea. Twenty-four percent discontinued ibrutinib at 13.8 months median follow-up; toxicity was the most common reason for discontinuation, though progression and/or transformation accounted for a larger proportion of discontinuations in <65 and those with del(17p13). Response rates were similar for <65 and those with del(17p13). However, patients with del(17p13) had inferior PFS and OS. Ibrutinib in the front-line setting has extended beyond the population in which it was initially studied and approved. This study highlights and compares important differences in ibrutinib dosing, treatment interruptions, toxicities, reasons for discontinuation, and survival outcomes in two important patient populations not studied in RESONATE-2.

Author List

Mato AR, Roeker LE, Allan JN, Pagel JM, Brander DM, Hill BT, Cheson BD, Furman RR, Lamanna N, Tam CS, Handunnetti S, Jacobs R, Lansigan F, Bhavsar E, Barr PM, Shadman M, Skarbnik AP, Goy A, Beach DF, Svoboda J, Pu JJ, Sehgal AR, Zent CS, Tuncer HH, Schuster SJ, Pickens PV, Shah NN, Rhodes J, Ujjani CS, Nabhan C

Author

Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenine
Age Factors
Aged
Chromosomes, Human, Pair 17
Clinical Trials as Topic
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Male
Middle Aged
Piperidines
Pyrazoles
Pyrimidines
Remission Induction
Retrospective Studies
Sequence Deletion
Survival Analysis
Treatment Outcome