Long-Term Studies Assessing Outcomes of Ibrutinib Therapy in Patients With Del(11q) Chronic Lymphocytic Leukemia

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 19; no. 11; pp. 715 - 722.e6
• Main Authors: Kipps, Thomas J., Fraser, Graeme, Coutre, Steven E., Brown, Jennifer R., Barrientos, Jacqueline C., Barr, Paul M., Byrd, John C., O’Brien, Susan M., Dilhuydy, Marie-Sarah, Hillmen, Peter, Jaeger, Ulrich, Moreno, Carol, Cramer, Paula, Stilgenbauer, Stephan, Chanan-Khan, Asher A., Mahler, Michelle, Salman, Mariya, Eckert, Karl, Solman, Isabelle G., Balasubramanian, Sriram, Cheng, Mei, Londhe, Anil, Ninomoto, Joi, Howes, Angela, James, Danelle F., Hallek, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019
• Subjects: Abnormal Karyotype; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Chromosome Deletion; Chromosomes, Human, Pair 11; Clinical Trials as Topic; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Male; Prognosis; Prognostic factors; Proportional Hazards Models; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Risk factors; Small lymphocytic lymphoma; Survival; Treatment Outcome; Small lymphocytic lymphoma; Survival; Prognostic factors; Risk factors
• ISSN: 2152-2650; 2152-2669; 2152-2669
• DOI: 10.1016/j.clml.2019.07.004

Certain genomic features, such as del(11q), expression of unmutated immunoglobulin heavy-chain variable region (IGHV) gene, or complex karyotype, predict poorer outcomes to chemotherapy in patients with chronic lymphocytic leukemia (CLL). We examined the pooled long-term follow-up data from PCYC-1115 (RESONATE-2), PCYC-1112 (RESONATE), and CLL3001 (HELIOS), comprising a total of 1238 subjects, to determine the prognostic significance of these markers in patients treated with ibrutinib. With a median follow-up of 47 months, ibrutinib-treated patients had longer progression-free survival (PFS) than patients treated in the comparator arm, regardless of genomic risk factors. Among patients treated with ibrutinib, we found that high-risk genomic features were not associated with shorter PFS (63-75% across all subgroups at 42 months) or overall survival (79-83% across all subgroups at 42 months). Surprisingly, we observed that ibrutinib-treated patients with del(11q) actually had a significantly longer PFS than ibrutinib-treated patients without del(11q) (42-month PFS rate 70% vs. 65%, P = .02). These analyses not only demonstrate that genomic risk factors previously associated with poor outcomes lose their adverse prognostic significance but also that del(11q) can be associated with a superior PFS with ibrutinib therapy. [Display omitted] A pooled analysis of 1238 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma from three phase 3 studies found that genomic risk factors were not associated with shorter progression-free survival (PFS) or overall survival for patients treated with ibrutinib. Ibrutinib-treated patients with del(11q) were found to have a longer PFS than those without del(11q). These results suggest less prognostic relevance for certain genomic risk factors with ibrutinib treatment.