Adverse Events

Adverse events were the most common reason for discontinuation or reduction in dose. “Those were unique for each drug. Atrial fibrillation was the most common reason for discontinuation of ibrutinib,” Nooruddin noted.

In the first line, 27% (328) of the veterans received ibrutinib. Adverse events accounted for nearly all of the 83 (25%) dose reductions with bleeds and rashes each responsible for 15% of reductions. Adverse events, primarily atrial fibrillation (20%), major bleeds (19%) and infection (11%), also drove two-thirds of the 108 (33%) drug discontinuations in the first line. Median duration of therapy was eight months and median overall survival from initiation of ibrutinib was 31 months, the researchers found.

Nearly two-thirds of the veterans with relapsed or refractory disease received ibrutinib as their second-line therapy. One-third of them required a dose reduction and another third discontinued the therapy, with adverse events responsible for 89% of the reductions and 63% of the discontinuations. Thrombocytopenia, arthralgia/myalgia, and infection each accounted for about 13% of reductions, while atrial fibrillation, infection and major bleed accounted for 11% to 19% of discontinuations. In the second line, median duration of therapy on ibrutinib was 12 months and median overall survival from initiation was 39 months.

Only 4% of veterans received idelalisib in the relapsed/refractory setting. Adverse events accounted for all dose reductions, which occurred in 16% of cases, with neutropenia the cause in half of the instances. Just over half of the discontinuations (84%) resulted from adverse events, including infection (27%) and pneumonia (18%). Median duration of therapy was five months from initiation.

At the same time, 7% of relapsed/refractory patients received venetoclax. Twenty-eight percent of patients required a dose reduction, all from adverse events, including neutropenia and thrombocytopenia, each responsible for 27%. Adverse events, including neutropenia, thrombocytopenia and infection also accounted for 41% of discontinuations, which occurred in 31% of the veterans. Follow up time was insufficient to calculate a meaningful overall survival rate in this group, the researchers reported.

“The biggest challenges in CLL today in the VA are managing our unique population with multiple comorbidities, determining how to sequence the drugs. The landscape has become very complex and oncologists need to be aware of all the choices and bring them into practice sooner rather than later,” Nooruddin said. With the pace of approvals for CLL drugs, staying up to date on the options has become a significant challenge, she added.

The new options represent the best hope for many patients, Noorudin noted, adding, “The landscape has changed drastically in the last five years, with novel agents becoming the treatment of choice in all but a very small percentage of patients in both the first-line and relapsed/refractory setting. New agents are moving upfront before the traditional chemotherapy that we’ve used for decades. That’s leading to fewer adverse events, as these agents are generally better tolerated.”

Frei CR, Le H, McHugh D, et al. Treatment Patterns and Outcomes of 1205 Patients on Novel Agents in the US Veterans Health Administration (VHA) System: Results from the Largest Retrospective EMR and Chart Review Study in the Real-World Setting. 2019