Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

Graeme A M Fraser, Asher Chanan-Khan, Fatih Demirkan, Rodrigo Santucci Silva, Sebastian Grosicki, Ann Janssens, Jiri Mayer, Nancy L Bartlett, Marie-Sarah Dilhuydy, Javier Loscertales, Abraham Avigdor, Simon Rule, Olga Samoilova, Miguel A Pavlovsky, Andre Goy, Anthony Mato, Michael Hallek, Mariya Salman, Monelle Tamegnon, Steven Sun, Anne Connor, Kerri Nottage, Natasha Schuier, Sriram Balasubramanian, Angela Howes, Paula Cramer, Graeme A M Fraser, Asher Chanan-Khan, Fatih Demirkan, Rodrigo Santucci Silva, Sebastian Grosicki, Ann Janssens, Jiri Mayer, Nancy L Bartlett, Marie-Sarah Dilhuydy, Javier Loscertales, Abraham Avigdor, Simon Rule, Olga Samoilova, Miguel A Pavlovsky, Andre Goy, Anthony Mato, Michael Hallek, Mariya Salman, Monelle Tamegnon, Steven Sun, Anne Connor, Kerri Nottage, Natasha Schuier, Sriram Balasubramanian, Angela Howes, Paula Cramer

Abstract

We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus ≤6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183-0.286]; p < .0001). Despite crossover of 63.3% of patients from the placebo plus BR arm to ibrutinib treatment upon disease progression, ibrutinib plus BR versus placebo plus BR demonstrated an overall survival benefit (HR 0.611 [95% CI 0.455-0.822]; p = .0010; median not reached in either arm). Long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone. Safety profiles were consistent with those known for ibrutinib and BR.

Keywords: 5-year follow-up; HELIOS phase 3 trial; Ibrutinib; overall survival; relapsed chronic lymphocytic leukemia.

Figures

Figure 1.
Figure 1.
Study design and follow-up assessments. IRC: independent review committee; PD: progressive disease. aDeletion 17p in ≥20% of examined cells. bStratified by purine analog refractory status (failure to respond or relapse in ≤12 months) and prior lines of therapy (1 line versus >1 line). cSimilar dosing to Fischer et al. [13]; bendamustine: 70 mg/m2 intravenously on Days 2–3 in Cycle 1 and Days 1–2 in Cycles 2–6; rituximab: 375 mg/m2 on Day 1 of Cycle 1 and 500 mg/m2 on Day 1 of Cycles 2–6. dAccording to 2008 International Workshop on Chronic Lymphocytic Leukemia criteria (Hallek et al. [17]).
Figure 2.
Figure 2.
Investigator-assessed PFS for ibrutinib plus BR versus placebo plus BR.
Figure 3.
Figure 3.
Investigator-assessed OS for ibrutinib plus BR versus placebo plus BR.
Figure 4.
Figure 4.
Prevalence of any grade TEAEs over time in the ibrutinib arm for (A) TEAEs of clinical interest and (B) TEAEs occurring in ≥30% of patients in the final analysis. aMajor hemorrhage TEAEs included serious/grade ≥3 hemorrhage and any grade central nervous system hemorrhage.

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Source: PubMed

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