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Ibrutinib improves survival in untreated chronic leukemia better than chemo

Written by Catharine Paddock PhD

Mon 7 December 2015

Read article on Medical News Today

 

Ibrutinib, a kinase inhibitor, is a significantly more effective frontline treatment for older patients with chronic lymphocytic leukemia or small lymphocytic lymphoma than traditional chemotherapy with chlorambucil.

 

This was the conclusion of the phase 3 RESONATE-2 study presented at the 2015 Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL, on Monday.
The multi-center, international randomized study followed 269 patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The results showed the 24-month overall survival rate for patients taking ibrutinib was 97.8% versus 85.3% for those on chlorambucil.

The study, led by Jan Burger, an associate professor in leukemia at the University of Texas MD Anderson Cancer Center in Houston, is published in the New England Journal of Medicine.

Prof. Burger says the study shows ibrutinib was superior to chlorambucil in patients who had received no prior treatments, as “measured by progression-free survival, overall survival, and response,” and it “also revealed significant improvements in hemoglobin and platelet levels.”

Ibrutinib is marketed as Imbruvica by its developer, Pharmacyclics, who part-funded the trial. The drug is approved in the US for use in patients with previously treated mantle cell lymphoma and CLL, and also for the treatment of Waldenström’s macroglobulinemia (WM), a rare form of cancer that begins in the body’s immune system.

 

Ibrutinib blocks key enzyme of leukemia cell receptor

CLL and SLL are types of non-Hodgkin lymphoma. They both affect a type of white blood cell called B-lymphocytes (B-cells), causing them to grow out of control. The only difference between CLL and SLL is where the cancer starts, so they are often lumped together as CLL.In CLL/SLL, cancer growth is driven by the B cell receptor (BCR), a molecule that sits on the surface of the leukemia cell and sends signals into the cell using enzymes, including Bruton’s tyrosine kinase (BTK).

Ibrutinib works by attaching to and blocking BTK, shutting down its signals and eventually triggering death of the leukemia cell. The drug also disables tissue anchor signals on the leukemia cells, so they are no longer attached to their nurturing environment and starve.

According to National Cancer Institute estimates, there will be 14,620 new cases of CLL in the US in 2015, and 4,650 deaths to the disease. CLL represents 0.9% of all new cancer cases among Americans and 0.8% of all cancer deaths.

Risk of death was 84% lower with ibrutinib than chemo

 

For the trial, the 269 previously untreated older patients with CLL or SLL were randomly assigned to receive either ibrutinib or chlorambucil, both orally. The patients were aged 65 years or older, and 44% had advanced stage disease.

Over a median follow-up of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil. Also, note the authors:

“The relative risk of progression was 84% lower and the relative risk of death was also 84% lower with ibrutinib than with chlorambucil.”

Of the patients receiving ibrutinib, 1 in 5 experienced side effects, including diarrhea, fatigue, cough and nausea.

“CLL is the most common adult leukemia in Western countries, and primarily affects older patients with a median age of 72 years at diagnosis,” Prof. Burger explains, as he sums up the significance of the study:

 

“In many countries, chlorambucil has remained the standard first-line therapy for such patients since the 1960s. This study paves the way for the use of ibrutinib in the front-line therapy setting.”

Earlier this year, Medical News Today learned how, following the discovery of a rare human antibody, researchers stumbled upon a way to make leukemia cells kill each other. Under lab conditions, they found 15% of cells were killed in 24 hours.

 

Written by Catharine Paddock PhD