The U.S. Food and Drug Administration (FDA) has approved Imbruvica (ibrutinib) plus Rituxan (rituximab) for the treatment of patients with a rare type of non-Hodgkin’s lymphoma called Waldenström’s macroglobulinemia (WM).
This represents the first and only chemotherapy-free combination treatment specifically indicated for the disease.
Imbruvica was first approved as a single-agent therapy for WM in January 2015, and is the only FDA-approved treatment specifically for this type of lymphoma. This compound works by blocking the activity of a protein called Bruton’s tyrosine kinase, triggering the death of cancerous B-cells.
Imbruvica’s recommended dose, either alone or combined with Rituxan, is 420 mg taken in pill form until disease progression or unacceptable toxicity. In combo therapy, Imbruvica is given before Rituxan, if both are given in the same day.
“We are pleased to have Imbruvica approved, both as a single agent and combination therapy with rituximab, to provide an additional efficacious treatment option for people living with Waldenström’s macroglobulinemia,” Thorsten Graef, MD, PhD, head of clinical development at pharmacyclics, said in a press release.
“We are proud of our robust clinical development program, and this new approval reflects our continuous commitment to exploring the full potential of Imbruvica’s mechanism of action for treating patients with diseases that have great unmet medical need,” he said.
The approval was based on results from the iNNOVATE Phase 3 trial (NCT02165397), which recruited 150 patients with previously untreated and relapsed or difficult-to-treat refractory WM.
Patients randomly received Rituxan in combination with either daily Imbruvica or a placebo.
The findings, published in The New England Journal of Medicine in the article “Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia,” showed that after a median follow-up of 26.5 months, 82 percent of patients in the Imbruvica combo group had no signs of disease progression. Patients on Rituxan alone, however, had a median progression-free survival of only 20 months. Overall, this represents an 80% reduction in the risk for disease worsening or death.
Imbruvica’s superiority was seen across patient subgroups. Among those who were never treated, Imbruvica reduced the risk of disease progression or death by 66%; for patients whose disease relapsed or was hard to treat, the risk dropped by 83%.
The most common adverse reactions of the combo therapy included bruising (37%), musculoskeletal pain (35%), hemorrhage (32%), diarrhea (28%), rash (24%), arthralgia (24%), nausea (21%), and hypertension (20%).
“The … study demonstrated persuasive clinical evidence supporting the efficacy of [Imbruvica] plus rituximab in Waldenström’s macroglobulinemia,” said Meletios A. Dimopoulos, lead study investigator. “This approval is a significant milestone for the WM community who have limited treatment options.”