With CML, Third Time Can Be a Charm

Chronic myeloid leukemia responds to third line TKI therapies

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) The course of chronic myeloid leukemia (CML) has changed substantially thanks to the use of a class of drugs called tyrosine kinase inhibitors (TKIs). How these drugs are being used is changing too.

Even after the first and second drug regimens fail against CML, a third attempt often works, according to a small recently published study out of Italy.

"Always be thorough when talking to your doctor about how you respond to drugs."

Antonella Vita Russo Rossi of the University of Bari, Italy and colleagues looked at the effects of third-line therapies for people with CML.

The first targeted TKI was Gleevec (imatinib), which is often prescribed for people newly diagnosed with chronic myeloid leukemia.

Studies have shown that the drug effectively works in over 80 percent of patients to eradicate all leukemia cells in what's called a complete cytogenic response.

The drug also dramatically reduces the number of leukemia cells in what's known as a major molecular response in about 70 percent of patients.

Then about 20 percent of patients do not respond to Gleevec, either from the beginning, or they become resistant to the drug over time.

That's when second generation TKIs - Sprycel (dasatinib) or Tasigna (nilotinib) - step in to take over the fight. These drugs treat about half of the people who have failed other drugs.

And what happens if these second-line drugs fail? All is not lost.

A small study involving 82 patients with CML looked at what happens when a third drug regimen is given. In this case, the patients were given either Sprycel or Tasigna after Gleevec no longer worked.

Here's what they learned:

  • A total of 34 patients failed on Tasigna and were started on Sprycel as third-line TKI therapy.
  • By contrast, 48 patients were switched from to Tasigna after Sprycel failed.
  • A cytogenetic response (reduction of leukemia cells) was seen in 32 of the 82 patients
  • Major molecular response (dramatic reduction of cells) occurred in 13 individuals.
  • The disease progressed in 12 people.
  • At the last follow-up, 85.4 percent of the patients were still alive, with the median overall survival being 46 months.

The authors wrote, "Our results show that third-line tyrosine kinase inhibitor therapy in chronic myeloid leukemia patients after failure of two prior sequential tyrosine kinase inhibitors may induce a response that, in some instances, could prolong overall survival and affect event-free survival."

This work was supported by Associazione Italiana contro le Leucemie, Linfomi e Mieloma (AIL)-Bari and MIUR (Ministero dell’Istruzione, dell’Universita’ e della Ricerca).

Reviewed by: 
Review Date: 
July 19, 2012
Last Updated:
February 21, 2013