Early Benefit Assessment of Ibrutinib Shows Conflicting Results

Ibrutinib evaluated in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinaemia, and mantle cell lymphoma.

A recent review of the drug ibrutinib reveals that there is no added benefit from the drug for patients who have chronic lymphocytic leukemia or Waldenström macroglobulinaemia, but found a benefit for patients with relapsed or refractory mantle cell lymphoma.

The drug manufacturer created a dossier at the request of the Federal Joint Committee (G-BA) since the turnover of the drug exceeded 50 million Euros in the previous 12 months. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined the dossier to assess whether or not the drug has an added benefit for patients compared with other therapies.

Chronic Lymphocytic Leukemia

Patients were separated into pretreated and treatment-naïve groups. Pretreated patients were separated into 2 subpopulations, which resulted in 3 research questions.

Pretreated patients with the option of chemotherapy were treated with chemotherapy. No relevant information for these patients was provided in the dossier.

Pretreated patients without the option of chemotherapy were treated with idelalisib. It was reported that there was a non-quantifiable advantage in mortality and also potentially lesser benefit of ibrutinib in morbidity. Health-related quality of life was decreased due to many serious side effects. A benefit was not proven for these patients.

Idelalisib was the comparator therapy for treatment-naive patients where chemotherapy was not suggested. The dossier presented a study that was irrelevant for the research question, so added benefit is not proven for this patient group either.

Waldenström Macroglobulinaemia

There was no added benefit of ibrutinib for treatment-patients, according to the assessment by IQWiG.

The manufacturer submitted a historical comparison based on uncontrolled studies, since no randomized controlled trials were conducted in pretreated patients. Due to lack of data, conclusions about the benefits of the drug were not able to be formed, so there was no reported benefit in these patients either.

Relapsed or Refractory Mantle Cell Lymphoma

Patients were grouped by who would receive temsirolimus as their optimized treatment and patients for whom this treatment was not recommended. Due to lack of data provided, an added benefit is not proven for patients who would likely not receive temsirolimus as their treatment.

However, the manufacturer provided data from a study where ibrutinib was compared with temsirolimus in the other patient group. There was no statistically different survival rate in the 2 groups, but ibrutinib showed positive effects on the health status of the patient and side effects.

For these patients, there was an indication of a major added benefit for those who receive temsirolimus as their optimized treatment.

The G-BA has final say on the extent of added benefit of the drug, the review concluded.