Long-term outcomes of the combination of ibrutinib, bendamustine and rituximab in relapsed/unresponsive CLL/SLL

This study aimed to investigate the long-term effectiveness of the combination of ibrutinib, bendamustine, and rituximab in relapsed/unresponsive chronic lymphocytic leukemia/small lymphocytic lymphoma. This study concluded that this combination was safe and effective in the long-term in these patients.  

Ibrutinib (Imbruvica) is a targeted therapy for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). It has shown good outcomes for these patients when given alone. Another, older treatment for CLL/SLL involves the BR regimen including chemotherapy drug bendamustine (Treanda) and immunotherapy drug rituximab (Rituxan).

It has been shown that ibrutinib added to BR treatment improves the survival of patients with relapsed or unresponsive CLL/SLL over 36 months. However, the long-term safety and effectiveness of this combination remain under investigation.

578 patients with relapsed or unresponsive CLL/SLL. Patients received 6 cycles of BR treatment and either daily ibrutinib or placebo. After the 6 BR cycles, they received either ibrutinib or placebo alone. Patients were followed up for an average of 63.7 months.  

Survival without cancer worsening was 65.1 months for the ibrutinib plus BR group compared to 14.3 months for the group that received placebo plus BR. Adding ibrutinib to BR was associated with a 77.1% lower risk of disease progression. 

Upon disease progression, 63.3% of patients from the placebo plus BR group crossed over to the ibrutinib plus BR group. Overall, at 60 months 75.7% of patients who received ibrutinib and BR were alive compared to 61.2% of the placebo and BR group. 87.2% of patients in the ibrutinib and BR group responded to treatment compared to 66.1% of the placebo and BR group.

90.2% of patients had at least one serious side effect in the ibrutinib and BR group. Most of these side effects appeared in the first 6 months. 7.7% of patients stopped treatment because of ibrutinib side effects. However, over time, this number decreased.

This study concluded that long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone for patients with CLL/SLL. 

This study was funded by Janssen, the manufacturer of ibrutinib.