MRD response in relapsed/refractory FL after obinutuzumab plus bendamustine or bendamustine alone in the GADOLIN trial

Abstract

We report assessment of minimal residual disease (MRD) status and its association with outcome in rituximab-refractory follicular lymphoma (FL) in the randomized GADOLIN trial (NCT01059630). Patients received obinutuzumab (G) plus bendamustine (Benda) induction followed by G maintenance, or Benda induction alone. Patients with a clonal marker (t [14;18] translocation and/or immunoglobulin heavy or light chain rearrangement) detected at study screening were assessed for MRD at mid-induction (MI), end of induction (EOI), and every 6-24 months post-EOI/discontinuation by real-time quantitative PCR. At MI, 41/52 (79%) patients receiving G-Benda were MRD-negative vs. 17/36 (47%) patients receiving Benda alone (p = 0.0029). At EOI, 54/63 (86%) patients receiving G-Benda were MRD-negative vs. 30/55 (55%) receiving Benda alone (p = 0.0002). MRD-negative patients at EOI had improved progression-free survival (HR, 0.33, 95% CI, 0.19-0.56, p < 0.0001) and overall survival (HR, 0.39, 95% CI, 0.19-0.78, p = 0.008) vs. MRD-positive patients, and maintained their MRD-negative status for longer if they received G maintenance than if they did not. These results suggest that the addition of G to Benda-based treatment during induction can significantly contribute to the speed and depth of response, and G maintenance in MRD-negative patients potentially delays lymphoma regrowth.

Obinutuzumab-atezolizumab-lenalidomide for the treatment of patients with relapsed/refractory follicular lymphoma: final analysis of a Phase Ib/II trial

“…In conclusion, this phase Ib/II study provides evidence of activity for the immunomodulatory triplet combination of G-atezo-len in R/R FL. The high rate of MRD negativity observed in our study is encouraging given the previously reported prognostic value of MRD status at EOI for long-term PFS in patients with R/R FL (GADOLIN trial) [ 39 ]. Although the sample size is too limited to draw definitive conclusions, data from this final analysis suggest that the addition of atezo to G-len may contribute to the durability of response.…”

Current Role of Functional Imaging in the Management of Lymphoma

“…Similarly in the GADOLIN study comparing bendamustine plus obinutuzumab versus bendamustine alone in rituximab refractory follicular and low-grade NHL [76], overall and complete response rates were comparable, yet the combination achieved longer PFS and overall survival. The improvement in outcome was associated with a greater and more prolonged reduction in MRD [77].…”

Does MRD have a role in the management of iNHL?

“…In MVA, MRD sta tus at EOI (85.7% G-B vs 55% B-arm), treat ment arm and FLIPI sta tus were strongly pre dic tive of PFS and, to a lesser extent, of OS. 23 In local ized FL, a monocentric expe ri ence dem on strated that after treat ment with local 24 to 30 Gy radiotherapy (RT), dis ap pear ance of cir cu lat ing BCL2/IGH+ cells in the PB and/or BM occurred in 50% (n = 20/40) of patients. 24 Additional treatment with R in MRD+ patients after RT or who had molec u larly relapsed dur ing the fol low-up achieved a molec u lar CR in 84% of cases: the 82-month PFS of MRD+ R-treated patients was sig nificantly bet ter than his tor i cal con trols, and the relapse prob a bil ity was sig nifi cantly lower in MRD− patients after RT or after R than that of patients remaining MRD+.…”