Real-World Evidence Reveals Patient Outcomes With Ibrutinib Treatment for CLL

For patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib monotherapy, real-world outcomes and treatment discontinuation rates were comparable to results from clinical trials. Researchers published their findings in Medicina.

“Randomized controlled trials (RCTs) and real-world studies provide distinct insight, sometimes contradictory, into ibrutinib therapy,” investigators said. “Furthermore, the real-life use of ibrutinib has sparked controversy on several other counts, including treatment adherence, adverse events (AEs), long-term outcomes, and high-risk factors.”

To elucidate real-world clinical outcomes, researchers conducted an observational retrospective study of 123 adults treated with ibrutinib for CLL and small lymphocytic lymphoma at Fundeni Clinical Institute in Romania. The study involved data from January 2016 to June 2021, and patients were excluded if they were enrolled in clinical trials or lacked information on date of death and last follow-up.

The investigators evaluated progression-free survival and overall survival, as well as overall response rate, drug toxicity, and any factors impacting survival and ibrutinib tolerability.

Thirteen percent of the participants received ibrutinib in the front-line setting, while 87% were treated for relapsed/refractory CLL. Of those who had received prior therapies, 39.3% of patients had been treated with fludarabine, and 86.9% had received anti-CD20 monoclonal antibodies such as rituximab, ofatumumab, and obinutuzumab. 

“The proportion of patients receiving both purine analog and anti-CD20 therapy was 37.4%,” researchers noted.

Median follow-up was 32 months. Findings showed median progression-free survival was 50 months, and the overall response rate was 86.2%. Overall survival was not reached.

“The age or number of previous therapies did not impact outcomes or tolerability,” investigators said.

Predictors for inferior progression-free survival included an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 2 or greater, as well as shorter time from initiation of last therapy (TILT) before ibrutinib. Shorter TILT also impacted overall survival but only in patients with relapsed/refractory CLL, findings showed.

Regarding safety, 82.1% of patients experienced drug-related AEs, with 30.9% of patients experiencing AEs of grade 3 or higher. The most common AE was infections (29.3%).

Nearly half (43.9%) of patients permanently discontinued ibrutinib during the study period. Disease progression (17.1%) and toxicity (8.9%) were the most common reasons for treatment discontinuation. 

Researchers found a higher risk of toxicity-related discontinuation among patients with a Cumulative Illness Rating Scale score ≥6. An ECOG PS ≥2 was associated with higher rates of permanent discontinuation and severe AEs.

“Our findings align with the results from ibrutinib clinical trials regarding outcomes, drug breaks, and permanent discontinuation rate. The ibrutinib-related AEs were common but manageable by dose reductions and treatment breaks,” researchers concluded. 

Study authors also determined long-term survival outcomes “were not impacted by age, prior treatment, or comorbidities. However, they seemed to be worse in patients with poor performance status, early relapse after pre-ibrutinib treatment, and those who permanently discontinued the drug.”

Reference:
Moldovianu AM, Stoia R, Vasilica M, et al. Real-world clinical outcomes and adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib: A single-center retrospective study. Medicina (Kaunas). 2023;59(2):324. doi: 10.3390/medicina59020324