Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma

• Published in: Leukemia Vol. 33; no. 4; pp. 969 - 980
• Main Authors: Fraser, G., Cramer, P., Demirkan, F., Silva, R. Santucci, Grosicki, S., Pristupa, A., Janssens, A., Mayer, J., Bartlett, N. L., Dilhuydy, M.-S., Pylypenko, H., Loscertales, J., Avigdor, A., Rule, S., Villa, D., Samoilova, O., Panagiotidis, P., Goy, A., Pavlovsky, M. A., Karlsson, C., Hallek, M., Mahler, M., Salman, M., Sun, S., Phelps, C., Balasubramanian, S., Howes, A., Chanan-Khan, A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2019; Nature Publishing Group
• Subjects: 631/67/1990/283/1895; 692/699/67/1990/283/1895; 692/700/565/1436/2185; Adenine - analogs & derivatives; Adolescent; Adult; Aged; Aged, 80 and over; Analysis; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bendamustine; Bendamustine Hydrochloride - administration & dosage; Cancer Research; Chronic lymphocytic leukemia; Clinical trials; Critical Care Medicine; Dosage and administration; Double-Blind Method; Drug therapy; Female; Follow-Up Studies; Hematology; Humans; Immunotherapy; Inhibitor drugs; Intensive; Internal Medicine; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphatic leukemia; Lymphocytic leukemia; Lymphoma; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Middle Aged; Minimal residual disease; Monoclonal antibodies; Non-Hodgkin's lymphomas; Ofatumumab; Oncology; Piperidines; Prognosis; Pyrazoles - administration & dosage; Pyrimidines - administration & dosage; Randomization; Recurrence (Disease); Rituximab; Rituximab - administration & dosage; Survival; Survival Rate; Targeted cancer therapy; Treatment outcome; Young Adult
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-018-0276-9

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1–45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159–0.265];
P
 < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454–0.935;
P
 = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (
P
 < 0.0001). Incidence of treatment-emergent adverse events (including grades 3–4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.