The results of the 6-year follow-up of the RELEVANCE study are announced! Can R2 surpass R-chemo in patients with follicular lymphoma?

Follicular lymphoma (FL) is an indolent lymphoma that originates in the center of follicular development and is low in malignancy but difficult to cure
.
The emergence of rituximab has pulled the treatment of FL into the era of
immunochemotherapy.
However, some patients are still unable to tolerate rituximab plus chemotherapy (R-chemo
).
The lenalidomide + rituximab (^R2) "chemo-free" regimen opens up a whole new treatment option
for FL patients.
Preliminary analysis of the RELEVANCE study suggests that the R² and R-chemo regimens are similar in patients with FL
.
Recently, researchers updated the latest 6-year follow-up data from the RELEVANCE study and published the results in the
Journal of Clinical Oncology.
The main contents are summarized as follows
.

Research Methods

Patients were randomly assigned 1:1 to receive^R2 or R-chemo (chemotherapy regimen chosen by the investigators: cyclophosphamide, doxorubicin, vincristine, and prednisone; Bendamustine; cyclophosphamide, vincristine, and prednisone), followed by maintenance therapy with rituximab
.
The primary endpoints of the study were complete remission at 120 weeks/unproven complete response (CR/CRu) and progression-free survival (PFS
).

Results of the study

Baseline characteristics

From December 2011 to November 2014, a total of 1030 patients were randomly assigned 1:1 to receive^R2 (n=513) or R-chemo (n=517), respectively, with similar baseline characteristics in both groups (Table 1).

In both groups, 350 patients (69%) and 357 patients (71%) completed 120 weeks of treatment
.

Table 1

efficacy

Results for the primary endpoints were similar
to those for the first interim analysis of the RELEVANCE trial.
^{The overall} response rate (ORR) was 61% and 65% for patients in the R2 and R-chemo groups, respectively, and the CR/CRu rate was 48% and 53%, respectively (Table 2
).

Table 2

There was no significant difference in PFS between the two groups (HR: 1.
03, 95% CI: 0.
84-1.
27, P=0.
78).

At median follow-up of 72.
0 months, neither group of patients achieved median PFS, with 60% and 59% 6-year PFS rates (Figure 1A).

Neither group achieved median overall lifetime (OS) and the estimated 6-year OS rate was 89% (Figure 1B
).

Figure 1

During the 72-month follow-up period, histological transformation
occurred in both the^R2 group (13/513) and the R-chemo group (11/517).
The 6-year cumulative conversion rate was 4.
4% and 3.
3%, respectively, and the annual conversion rate was 0.
68% and 0.
45%,
respectively.

In addition, the results of the subgroup analysis of PFS were consistent
with the first interim analysis.
The efficacy of the^R2 regimen remains independent of conventional prognostic factors, including disease stage, FLIPI, megafocal disease, and age
.
Disease progression over 24 months (POD24) was associated with worsening 5-year survival (POD24: 59.
5%, 95% CI 49.
9 to 67.
8; control group: 95.
2%, 95% CI 93.
3 to 96.
6; P<0.
0001).

In patients with POD24, the 5-year survival rate of the^R2 regimen and the R-chemo regimen was similar (59% vs 60%, P=0.
9693).

security

The overall safety was consistent with the results of the first mid-term analysis of the RELEVANCE trial, with no new safety signals
detected.
Fifteen patients (compared to 12 in 2017) reported ≥1 adverse event (TEAE) during grade 5 therapy, 9 in the^R2 group (6 in 2017) and 6 in the R-chemo group (no change from 2017).

A second primary malignancy occurred in 57 patients in the R2 group (compared to 38 in 2017) (11%), and 67 patients in the R-chemo group (48 in 2017) (13%)
.
A total of 114 patients (66 in 2017) died, 59 in the^R2 group and 55 in the R-chemo group
.

Conclusion of the study

PFS and OS were similar in the^R2 and R-chemo groups, suggesting that the R² and R-chemo regimens had similar
efficacy in patients with initial FL.
In addition, the overall safety of the two groups is consistent with the results of the first interim analysis, although the safety of the R2 scheme is different from that of the R-chemo scheme, but the safety of the^R2 scheme is controllable
.
Overall, the^R2 regimen has similar efficacy and safety to the R-chemo regimen and can be used as a chemotherapy-free alternative to the R-chemo regimen for patients with newly-treated FL
.

Reference source:

Morschhauser F, Nastoupil L, Feugier P, et al.
Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma.
J Clin Oncol.
2022 Aug 10: JCO2200843.
doi: 10.
1200/JCO.
22.
00843.

Approval number CN-102520, the content of this material is supported by AstraZeneca and is for the information of healthcare professionals only and is not intended for promotional purposes