Different From RCTs

With the increased use of these newer therapies, Nooruddin and her colleagues wanted to learn more about how they were used in daily practice and how well they were tolerated.

The researchers manually reviewed the choice of therapy for 1,366 veterans treated with a novel agent looking for any changes from the recommended dosage and duration. They focused on the three novel therapies used most often during the study period, October 2013 to March 2018. Those were ibrutinib, idelalisib and venetoclax. The final analysis included 1,205 veterans.

“We conducted one of the first real world studies for CLL,” noted Nooruddin. “We found that dose reductions and discontinuations occurred at a significantly higher rate than reported in the randomized clinical trials.”

The veterans in the study also differed significantly from the patients in the clinical trials, she observed. First, nearly all (98%) of the veterans were male. “The other interesting thing about the population was their age. The median age was 72 for all novel agents and approximately 10% were more than 89 years of age, which was the upper limit in the trials. The oldest age we treated was 96 in all arms,” Nooruddin said. “Also, the median Charleston score was 5 to 6, which was higher than in the clinical trials.”

“Because of these differences between the clinical trials and our study, which had older patients with multiple comorbidities, we saw more adverse events and higher discontinuation rates. In our study, for instance, 25% discontinued ibrutinib versus the 13% seen in the trial,” she added.

While different from the clinical trials, the VA’s rates of dose reduction and discontinuation are “similar to that seen in other healthcare systems in the country, despite our patient population’s unique comorbidities,” Nooruddin said. “The results reflect that care in the VA is similar to other healthcare systems in the U.S.”

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