The addition of ibrutinib to standard-of-care chemoimmunotherapy significantly prolongs progression-free survival in older patients with previously untreated mantle-cell lymphoma, according to an international trial presented at this year’s ASCO congress. 

Results from the double-blind phase III SHINE trial, which was simultaneously published in the NEJM, found the median progression-free survival (PFS) was 6.7 years with ibrutinib in combination with bendamustine-rituximab and rituximab maintenance (n=261), compared to 4.4 years  for those who received a placebo with bendamustine-rituximab and rituximab maintenance (n=262) (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.01).

“The separation of the progression-free survival curves occurred within the first year after the initiation of treatment, and the benefit was durable throughout the median follow-up of 7 years,” noted the research team which included Professor Judith Trotman from Concord Repatriation General Hospital in Sydney. 

In terms of secondary endpoints the complete response rate was 65.5% in the ibrutinib group compared to 57.6% in the placebo group, a finding that was not statistically significant. Overall survival was also similar between the groups; 55% in the ibrutinib group at 7 years and 56.8% in the placebo group (hazard ratio for death, 1.07; 95% CI, 0.81 to 1.40) .

Adverse events of grade 3 or 4 during the treatment period occurred in 81.5% of the patients in the ibrutinib group and in 77.3% of those in the placebo group. The incidence of infections during the maintenance period were higher in the ibrutinib group than in the placebo group. 

“In rare cases, infections were fatal, which suggests the continued need for vigilance in identifying and managing these adverse events,” the researchers said. 

“Overall, despite more adverse events and related discontinuations in the ibrutinib group than in the placebo group, the finding that patient-reported outcomes were similar in the two groups supports an acceptable safety profile of the trial combination,” they commented.

The research group noted that the trial was not designed to answer the question of whether first-line combination therapy with ibrutinib, bendamustine, and rituximab would be superior to ibrutinib therapy given after bendamustine and rituximab treatment. 

“Given the shorter progression-free survival with current standard-care chemoimmunotherapy options, a prolongation of progression-free survival in response to primary therapy may provide patients with an improved opportunity for durable disease control in order to prevent or delay relapse,” they wrote. 

The SHINE trial was supported by Janssen Pharmaceuticals NV & Pharmacyclics LLC, an AbbVie Company.