Chronic lymphocytic leukemia (CLL) is a type of blood cancer where the bone marrow makes too many abnormal lymphocytes (a type of white blood cell). These abnormal cells can build up in the blood, bone marrow, lymph nodes, and spleen. Over time, the number of abnormal cells increases while the number of healthy blood cells decreases, which can lead to infection, anemia, and bleeding. CLL is typically a slow-growing cancer, but in some people it can be more aggressive. It is one of the most common types of leukemia in adults.
Ibrutinib is a targeted therapy drug used for treating certain blood cancers like CLL. It works by blocking Bruton’s tyrosine kinase (BTK), an enzyme that helps abnormal B cells grow and survive. By blocking BTK, ibrutinib can help kill cancerous B cells while leaving healthy cells alone. Ibrutinib was approved by the FDA in 2013 specifically for treating CLL. It has shown great promise in clinical trials for improving progression-free survival and overall survival in CLL patients. However, it is not yet considered a cure. Let’s explore the evidence on ibrutinib for CLL.
How is ibrutinib used for CLL?
Ibrutinib is taken orally once per day. It is typically the first treatment used (first-line therapy) for CLL, either alone or sometimes combined with obinutuzumab. For people whose cancer comes back after initial treatment, ibrutinib can be used as a second-line therapy. It may also be used first-line for high-risk CLL patients, such as those with 17p deletion. Ibrutinib is approved for treating CLL with or without 17p deletion. It has been revolutionary in the treatment of high-risk CLL.
What are the results from clinical trials?
Several large clinical trials have shown impressive results for ibrutinib in CLL:
First-line treatment
In a phase 3 trial of 269 untreated older patients, ibrutinib alone led to an estimated 89% progression-free survival at 36 months. The comparator arm using chemoimmunotherapy (bendamustine + rituximab) had only 34% progression-free survival at 36 months.
A trial of ibrutinib + obinutuzumab in previously untreated CLL reported 84% progression-free survival at 3 years, compared to only 36% with chlorambucil + obinutuzumab.
Relapsed/Refractory CLL
In a study of 195 relapsed/refractory CLL patients, ibrutinib achieved an overall response rate of 71% and median progression-free survival of 13.9 months.
Another study of relapsed/refractory CLL reported a 63% response rate to ibrutinib and estimated 22-month progression-free survival rate of 75%.
A comparative trial found ibrutinib significantly improved progression-free and overall survival over ofatumumab in relapsed/refractory CLL.
High-Risk CLL
In multiple trials of high-risk CLL patients with 17p deletion, ibrutinib has achieved overall response rates of 71-84% and 2-year progression-free survival around 41-68%.
This demonstrates ibrutinib’s ability to produce durable remissions even in difficult-to-treat CLL.
What are the side effects?
Ibrutinib is generally well tolerated, especially compared to chemotherapy. Common side effects can include:
– Diarrhea
– Muscle/joint pain
– Rash
– Bruising or bleeding
– Fatigue
– Nausea
– Fever
More severe side effects may include infections, heart rhythm problems, and high blood pressure.
There is also a small risk of bleeding or bruising from the drug’s mechanism of action. Patients on ibrutinib require regular blood monitoring to check for cytopenias (low blood cell counts).
Overall, most patients are able to manage the side effects of ibrutinib. It has a favorable side effect profile compared to traditional chemotherapy regimens.
Does ibrutinib cure CLL?
Based on the results from clinical trials, ibrutinib can lead to very durable remissions, even in high-risk patients. Many patients remain progression-free on ibrutinib for years. However, most experts consider ibrutinib unlikely to “cure” CLL for several reasons:
– Patients typically stay on ibrutinib continuously, rather than completing a finite course of treatment. Stopping the drug often leads to disease progression.
– Some CLL cells may persist at very low levels even during ibrutinib treatment. If therapy is stopped, these cells may proliferate again.
– Over several years on ibrutinib, some patients develop resistance mutations that make CLL cells insensitive to ibrutinib’s effects. This leads to relapse.
– Single-agent ibrutinib has not shown ability to eradicate minimal residual disease (small numbers of lingering cancer cells). Deeper remissions are seen when ibrutinib is combined with other therapies.
So while not considered curative, ibrutinib can keep CLL controlled for prolonged periods, essentially transforming CLL into a “chronic manageable condition” for many patients. The side effects are tolerable enough for continuous use. Clinical trials are exploring whether using ibrutinib in combinations or sequences with other therapies may further improve results.
Conclusion
Ibrutinib has been a game-changing therapy for CLL, able to induce remissions even in high-risk patients and those with relapsed/refractory disease. It has improved survival outcomes and quality of life compared to older regimens. While ibrutinib alone is not considered curative, it offers durable disease control that may last for many years when given continuously. Research is ongoing to identify optimal combination and sequencing strategies with ibrutinib to further improve CLL outcomes. For now, ibrutinib remains one of the most effective first-line therapies for CLL.