Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia

By J. Byrd, Jennifer R. Brown, S. O'brien, J. Barrientos, N. Kay, N. Reddy, S. Coutre, C. Tam, S. Mulligan, U. Jaeger and 25 more. New England Journal of Medicine, 2014

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Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)

Subfields: Genetics, Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/c6f4897e59e7e00117e30176dbce861205a3e022

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Citations in the corpus

Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. (2016, neutral): “Richter’s transformation 38 (28) 38 (5) 25 (33) 25 (6) 13 (22) 13 (3)”
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia (2015, neutral): “Upper respiratory tract infection 4 (3)”
Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia (2019, methodology): “332 Were eligible and started assigned treatment 352 Were included in the safety analysis 151 Were eligible and started assigned treatment 158 Were included in the safety analysis 22 Were ineligible or did not start assigned treatment 22 Were ineligible 17 Did not have translocation (11;14) tested b”
Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2015, positive): “– BCL2 antagonists alone or in combination within a clinical study – Bruton’s tyrosine kinase inhibitor ibrutinib [23] – PI3K inhibitor idelalisib in combination with rituximab [24] – Other chemoimmunotherapy combinations should only be administered if TP53 deletion/mutation was excluded (Figure 2).”
Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia (2015, neutral): “Platelet count ≤100,000/mm3 35 (26) 28 (21)”
Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. (2015, neutral): “Median platelets, 3 10(9)/L (range) 113 (32-217) 105 (2-310) 105 (2-310) #100 3 10(9)/L, n (%) 12 (39) 49 (49) 61 (46)”