Obinutuzumab, rituximab improve PROs in follicular lymphoma patients

The addition of obinutuzumab or rituximab to chemotherapy* (O-CT or R-CT, respectively) similarly led to HRQoL** improvements in patients with previously untreated advanced follicular lymphoma (FL), according to the phase III GALLIUM study.

In the primary analysis, progression-free survival (PFS) improved with O-CT vs the current standard-of-care, R-CT, for first-line FL. [New Engl J Med 2017;377:1331-1344] The updated analysis also revealed consistent efficacy and safety findings. [Blood 2018;132:1597]

“[However, FL] treatment … can often have a more negative impact on the patient than the disease itself … [As such,] achieving improvements in PROs*** is just as important as improving clinical outcomes such as PFS,” said the researchers.

A total of 1,202 participants were randomized 1:1 to receive O-CT or R-CT as induction therapy and maintenance regimen for those who achieved a partial response for 2 years or until disease progression. HRQoL was assessed using the FACT^#-Lymphoma questionnaire, including the FACT-General (PWB, FWB, EWB, and SWB^##) and lymphoma-specific (LYMS) subscales, as well as the FACT-Lymphoma composite summary scales (Trial Outcome Index and Total [TOI and TOT, respectively]). Higher FACT-Lymphoma scores signify improved functioning, HRQoL, and health status. [Ann Hematol 2020;99:2837-2846]

First assessment, maintenance phase

At first assessment (cycle 3, day 1), both O-CT and R-CT arms had negative mean changes from baseline PWB (–0.21 vs –0.91) and FWB scores (–0.06 vs –0.30). “[These declines] indicate that further measures should be taken during early induction to ensure the provision of [O-CT] does not negatively influence physical and functional well-being,” the researchers explained.

Conversely, there were increases in EWB (1.36 vs 1.49) and LYMS scores (2.73 vs 2.04) in both O-CT and R-CT arms, and more than a third of participants achieved MID^###.

By month 2 of the maintenance phase, mean changes from baseline LYMS score increased in both O-CT and R-CT arms (4.52 vs 4.80), as did the TOI (7.17 vs 6.22), and TOT scores (8.13 vs 8.40). Nearly half of participants achieved MID by this time.

Follow-ups

By month 48, both arms saw modest increases in PWB, FWB, and EWB scores. Mean changes from baseline LYMS, TOI, and TOT scores also stabilized in both O-CT and R-CT arms (4.76 vs 4.50 [LYMS], 8.51 vs 7.23 [TOI], and 9.48 vs 8.98 [TOT]).

More than half of participants continued to achieve MID based on the LYMS (54 percent vs 56 percent), TOI (52 percent vs 50 percent), and TOT scores (50 percent vs 48 percent), suggesting sustained improvements from month 2.

“At no timepoint up to month 48 was the average HRQoL of [O-CT recipients] clinically worse than those receiving R-CT,” they said. Moreover, the improved FACT-General subscale scores and the achievement of MID suggest that “improvements in well-being were not abrogated by the increased number of treatment-related side effects reported in patients receiving O-CT vs R-CT.”

The LYMS improvements also imply that lymphoma-related symptoms improved with both agents to a degree that is recognizable to patients, consequently driving the TOI and TOT improvements. “Importantly, this was despite the higher AE rates observed in the O-CT arm [in] the primary and updated analyses,” they noted.

PWB scores in both arms continued to increase beyond month 48, with MID achieved between months 72 and 84. TOI and TOT scores also continued to increase up to month 84.

Clinical outcomes, PROs equally as important

“Within the context of improved PFS, these results further support the positive benefit-risk balance of O-CT over R-CT in previously untreated patients with FL,” said the researchers. “[However, the lack of] clear differences between groups at any timepoint … [suggest] that both treatments reduced lymphoma-related symptoms, and treatment-related side effects did not abrogate improvements in well-being.”

As such, future FL trials should explore both clinical outcomes and PROs. Timing of HRQoL evaluation should also be taken into context in future trials, as this may influence the differences between regimens. “[T]he length of time between assessments may have missed changes that occurred in symptom burden during the initial weeks of treatment,” they added.