Updated long-term data AUGMENT R2 efficacy for R/R iNHL

In the longer-term follow-up of the phase III AUGMENT trial, the lenalidomide-rituximab (R²) combination trumped the rituximab-placebo regimen (control) for the treatment of relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL).

“After over 5 years, R² continued to demonstrate superior efficacy over control as measured by the primary endpoint of progression-free survival (PFS),” said Dr John Leonard from Weill Cornell Medicine and New York Presbyterian Hospital, New York, New York, US, at ASH 2022.

At a median follow-up of 65.9 months, PFS was nearly twice as long with R² vs control (median 27.6 vs 14.3 months; hazard ratio [HR], 0.50; p<0.0001). [ASH 2022, abstract 230]

 

OS, TTNLT

Although median overall survival (OS) was not reached in both arms, R² had an advantage over control (83 percent vs 77 percent; HR, 0.59; p=0.0285). “There are not that many studies showing an OS benefit in recurrent FL* and MZL*, so … it is notable that we do have a difference [between] these regimens with respect to OS in [this setting],” noted Leonard.

TTNLT** was also better with R² vs control (73.1 vs 31.8 months; HR, 0.53; p<0.0001). “This is a bit subjective because [treatment decisions are] based on clinical and physician and patient choices. Nonetheless, the difference between arms was quite substantial,” he continued.

Fewer R² recipients had ≥1 subsequent therapy vs those in the control arm (41 percent vs 61 percent). “[Of note,] this was a patient population that have gone a median 2 years from their prior therapy. [Hence, the TTNLT results do] suggest that the R² benefit … seems to extend beyond completion of treatment and seems better than their prior therapy,” Leonard said.

The population comprised 358 individuals (median age 63 years, 48 percent male) with FL grade 1–3a or MZL with ≥1 prior*** regimens, documented R/R disease but not refractory to rituximab. Participants were randomized 1:1 to R² or control for up to a year. Lenalidomide 20 mg was given on days 1–21 (cycles 1–12). Rituximab 375 mg/m² was administered on days 1, 8, 15, and 22 during cycle 1 and on day 1 during cycles 2–5. They were followed up every 6 months for up to 5 years.

 

Safety, SPMs, transformations

Grade 3/4 treatment-emergent adverse event (TEAE) rate was higher with R² vs control (69 percent vs 32 percent). This is not surprising, said Leonard, as toxicities are more likely upon the addition of lenalidomide.

The incidence of any-grade TEAE leading to dose interruption was also higher in the R² vs the control arm, both with lenalidomide/placebo (64 percent vs 26 percent) and rituximab (34 percent vs 21 percent).

While the numbers are relatively small, fewer SPMs^# were reported with R² vs control (n=13 vs 21). “One might speculate that this has something to do with needing less subsequent therapies, [but] it is hard to say,” Leonard noted. “This will be interesting to follow, but certainly … lenalidomide was better or at least the same [as placebo] and was not associated with more SPMs.”

There were also fewer histologic transformations in the R² vs the control arm (n=10 vs 15). “Again, the numbers are small so we cannot draw big conclusions, but this is a bit encouraging,” he said.

There were fewer deaths due to disease with R² vs control (n=26 vs 47), which is consistent with the OS benefit.

 

R² as SoC?

The initial AUGMENT results have already reflected superior efficacy and higher overall and complete response rates with R² vs control, leading to the approval of R² for previously treated FL or MZL in the US, Japan, and Brazil, and for FL in Europe. [J Clin Oncol 2019;37:1188-1199; packageinserts.bms.com/medguide/medguide_revlimid.pdf; packageinserts.bms.com/gb/prescribing-information/revlimid-lymphoma-gb.pdf]

“[Taken together, the current findings] provide further support for the use of the R² regimen as standard of care for patients with R/R iNHL,” Leonard concluded.