For older adults with relapsed follicular lymphoma (FL) or chronic lymphocytic leukemia (CLL), idelalisib may come with higher rates of dose reduction and toxicity than initially seen in clinical trials, according to a study recently published in JAMA Oncology.
To determine the real-world outcomes for idelalisib among older adults, the study researchers evaluated the outcomes of trial participants 65 years or older from 2 pivotal clinical trials (ie, study 101-09 and study 312-0116) and compared them to the outcomes of real-world Medicare beneficiaries 65 years or older.
A total of 26 participants were included from study 101-09, which was a single-arm, phase 2 trial that led to the accelerated approval of idelalisib for relapsed or refractory FL, and 89 participants were included from study 312-0116, which was a phase 3 randomized trial that led to the accelerated approval of idelalisib plus rituximab for relapsed CLL.
As for the real-world patients, 305 Medicare beneficiaries with FL who received idelalisib and 294 with CLL who received idelalisib plus rituximab were identified and included.
The analysis revealed that Medicare beneficiaries had different treatment outcomes compared with the trial participants. Those different treatment outcomes included having more comorbidity and approximately double the number of Medicare beneficiaries who needed dose reductions compared with trial participants, both for patients with CLL (32.6% vs 18.0%, respectively; P =.003) and FL (38.5% vs 16.1%, respectively; P =.02).
The duration of treatment was also significantly shorter only for Medicare beneficiaries with CLL compared with trial participants (173 vs 473 days, respectively; P <.001), and the rate of fatal infections per 100 person-years was significantly higher (18.4 vs 9.8, respectively; P =.04).
In addition, the risk for a fatal infection during treatment was 2.11-fold higher (95% CI, 1.44-3.10) for Medicare beneficiaries who had been hospitalized for an infection within 6 months before starting idelalisib.
This finding was uncovered despite a March 2016 recommendation for Pneumocystis jirovecii pneumonia prophylaxis in patients who received idelalisib. Overall, the rate of prophylaxis remained low after the recommendation, with only 25% of FL and 37% of CLL beneficiaries receiving prophylaxis.
The study researchers described these outcome differences as “substantial,” explaining that “selective eligibility criteria and closer monitoring of trial patients may be responsible for limited generalizability of trial data to clinical practice.”
Disclosure: Dr Bird reports being employed by the US Food and Drug Administration.
Bird ST, Tian F, Flowers N, et al. Idelalisib for treatment of relapsed follicular lymphoma and chronic lymphocytic leukemia: A comparison of treatment outcomes in clinical trial participants vs Medicare beneficiaries [published online December 19, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.3994