Long-Term Studies Assessing Outcomes of Ibrutinib Therapy in Patients With Del(11q) Chronic Lymphocytic Leukemia. Clinical lymphoma, myeloma & leukemia Kipps, T. J., Fraser, G., Coutre, S. E., Brown, J. R., Barrientos, J. C., Barr, P. M., Byrd, J. C., O'Brien, S. M., Dilhuydy, M., Hillmen, P., Jaeger, U., Moreno, C., Cramer, P., Stilgenbauer, S., Chanan-Khan, A. A., Mahler, M., Salman, M., Eckert, K., Solman, I. G., Balasubramanian, S., Cheng, M., Londhe, A., Ninomoto, J., Howes, A., James, D. F., Hallek, M. 2019


BACKGROUND: 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).PATIENTS AND METHODS: 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.RESULTS: 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).CONCLUSION: 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.

View details for DOI 10.1016/j.clml.2019.07.004

View details for PubMedID 31447270