A combination of Imbruvica (ibrutinib) and Rituxan (rituximab) significantly extends the time to disease worsening or death in patients with a rare type of lymphoma called Waldenström’s macroglobulinemia, a Phase 3 trial shows.
While the approach failed to improve survival, the findings prompted Janssen — Imbruvica’s maker — to submit a supplemental new drug application with the U.S. Food and Drug Administration to expand Imbruvica’s use in combination with Rituxan for Waldenström’s macroglobulinemia.
Results from the iNNOVATE Phase 3 trial (NCT02165397) were recently presented in an oral presentation, “Randomized phase 3 trial of ibrutinib/rituximab vs placebo/rituximab in Waldenström’s macroglobulinemia,” at the 2018 American Society of Clinical Oncology Annual Meeting in Chicago.
At the same time, The New England Journal of Medicine published the findings of the study in an article titled “Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia.”
Imbruvica, jointly developed and marketed by Janssen and Pharmacyclics, is the only treatment approved by the FDA specifically for this disease. It works by blocking the activity of a protein called Bruton’s tyrosine kinase, inhibiting the survival of B-cell cancers.
The multicenter iNNOVATE trial was designed to test if adding Imbruvica to Rituxan could delay disease progression or death in Waldenström’s macroglobulinemia patients who had either failed or had not received any prior therapies. It included 150 patients who were randomized to receive Rituxan in combination with either daily Imbruvica or a placebo.
After a median follow-up of 26.5 months, more than half of the patients in the Imbruvica combination group still showed no signs of disease progression. Patients on Rituxan alone, however, had a median progression-free survival of only 20 months. This represents an 80% reduction in the risk for disease worsening or death, the researchers said.
Imbruvica’s superiority was seen across multiple patient subgroups. For patients who had not received prior therapies, Imbruvica reduced their risk for disease progression or death by 66%. For those with relapsed or refractory disease, the risk dropped by 83%.
Patients with genetic mutations linked to poor prognosis — MYD88L265P and CXCR4WHIM — also had at least a 79% lower risk of disease progression.
“Not only was there marked statistical and clinical difference in the efficacy compared to rituximab monotherapy, but the combination of ibrutinib and rituximab did not result in any unanticipated safety signals,” Meletios A. Dimopoulos, MD, professor at the National and Kapodistrian University of Athens‘ School of Medicine and lead iNNOVATE study investigator, said in a press release.
Patients treated with the combo therapy also showed better overall response rates and major response rates than with Rituxan alone. However, survival rates after 30 months were similar between both groups — 94% in the combination group and 92% in the Rituxan group.
“The results from the iNNOVATE study provide physicians with compelling evidence to consider Imbruvica in combination with rituximab for the treatment of patients living with Waldenström’s macroglobulinemia, across all lines of treatment and patient subtypes, offering the potential for a chemotherapy-free option for these patients,” said Craig Tendler, MD, vice president of clinical development and medical affairs at Janssen Research & Development. “We look forward to working with the U.S. FDA to bring Imbruvica to additional patients living with Waldenström’s macroglobulinemia who may benefit from this treatment option.”