Ibrutinib as a treatment option for relapsed or refractory CLL

This study examined the effectiveness of ibrutinib (Imbruvica) in treating relapsed or refractory chronic lymphocytic leukemia (CLL). Researchers reported that ibrutinib was associated with low disease progression rates at low and high doses.

Chemotherapy and immunotherapy are usually the first-line treatments of CLL. In cases of a relapse (return of the disease) of CLL, alternative treatment options are usually explored. This is because many patients develop a resistance to standard therapy over time.

Tyrosine kinase inhibitor therapy is a type of targeted therapy that blocks signals needed for tumors to grow and spread. This includes the Bruton tyrosine kinase inhibitor ibrutinib. Ibrutinib blocks a signal that keeps the CLL cell alive. This treatment is especially helpful in CLL that is hard to treat, such as when there are certain genetic abnormalities due to CLL. It may also be an effective treatment option for relapsed CLL.

The aim of this study was to examine the effectiveness of ibrutinib for relapsed CLL.

85 CLL patients were included in this study. Patients had either relapsed or were no longer responding to standard therapy. 65% had advanced-stage disease and had undergone an average of 4 previous therapies. 51 patients were treated with a 420 mg daily dose of ibrutinib (low dose). 34 patients were treated with 840 mg of ibrutinib daily (high dose). Treatment outcomes were followed for an average of 20.9 months.

64% of patients were still receiving treatment after 20.9 months. 36% had discontinued treatment.

Treatment response was 71% in the low dose group. This included 2 complete responses and 34 partial responses. Treatment response was the same (71%) in the high dose group. Of these, all were partial responses. 20% achieved a partial response with lymphocytosis (persistent lymphocytes in the blood). The response to ibrutinib was not affected by the presence of advanced-stage disease.

33% of patients presented with the genetic abnormality of a deletion of the 17p13.1 chromosome. 36% of patients had 11q22.3 deletions. For patients with a 17p13.1 deletion, treatment response was 68%. This was similar to patients without this deletion (71%).

The overall survival rate (proportion who have not died from any cause since treatment) at 26 months was 83%. 75% of patients were progression-free at 26 months. 11 patients (13%) developed disease progression during the study period. Of these, 7 had transformed into a fast-growing type of lymphoma (Richter’s syndrome). The average time from CLL diagnosis to this transformation was 98 months. Of the 11 patients with disease progression, 10 (91%) had a 17p13.1 or a 11q22.3 deletion (a type of genetic alteration).

Most side effects were considered mild. The most common were diarrhea, fatigue, and upper respiratory tract infection. Serious side effects included pneumonia (in 10 patients) and dehydration (in 5 patients). 2 patients in the low dose group and in 4 patients in the high dose group discontinued treatment due to side effects.

Researchers concluded that ibrutinib is a safe and effective treatment for relapsed or persistent CLL.

Larger studies that compare the effectiveness of ibrutinib with other treatments or placebo (control drug with no active effect) are needed to confirm these results.