MINIMAL RESIDUAL DISEASE AND OUTCOMES IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (FL) IN THE PHASE III GADOLIN TRIAL OF OBINUTUZUMAB AND BENDAMUSTINE VS BENDAMUSTINE

Abstract

Introduction: Minimal residual disease (MRD) response after first-line treatment of FL may predict outcome; however, data are limited in the relapsed/refractory (r/r) setting. We previously described MRD assessment in r/r FL in the randomised GADOLIN study (NCT01059630; Pott C, et al. ASH 2015). Here, we report updated results for MRD status for the full population. MRD kinetics postinduction with respect to treatment efficacy and prognosis are reported for the first time. Method(s): Patients (pts) received obinutuzumab (G) + bendamustine (B) (90 mg/m2) followed by G maintenance, vs B (120 mg/m2) alone. MRD was analysed by t(14;18) real-time quantitative PCR (RQ-PCR) and/or allele-specific immune gene (IGH or IGK) RQPCR in pts with a clonal marker at diagnosis: at mid-induction (MI), end of induction (EOI) and 6-monthly intervals to 24 months post EOI/discontinuation. MRD status was negative (i.e. MRD response achieved) if RQ-PCR and subsequent nested PCR were negative. Result(s): of 335 randomised pts with FL, a clonal marker was detected in 228/319 (71%) pts with baseline samples (baseline-evaluable population, BEP). Compared with the BEP, the population with a detectable marker was enriched for higher stage, worse FLIPI and bone marrow (BM) involvement. MI and EOI samples were analysed for 88 and 118 pts, respectively. MRD negativity in peripheral blood (PB) occurred early during induction and was more frequent with G + B: 41/52 (79%) pts were MRD negative at MI vs 17/36 (47%) in the B arm (p = 0.0029). At EOI, MRD responses further increased: 54/63 (86%) pts receiving G + B achieved MRD negativity in PB and/or BM vs 30/55 (55%) in the B arm (p = 0.0002) (Table ). Pts with complete/ partial response who were MRD negative at EOI had improved PFS and OS vs MRD-positive pts; hazard ratios (adjusted for treatment): PFS, 0.33 (95% CI 0.19-0.56, p Result(s): of 335 randomised pts with FL, a clonal marker was detected in 228/319 (71%) pts with baseline samples (baseline-evaluable population, BEP). Compared with the BEP, the population with a detectable marker was enriched for higher stage, worse FLIPI and bone marrow (BM) involvement. MI and EOI samples were analysed for 88 and 118 pts, respectively. MRD negativity in peripheral blood (PB) occurred early during induction and was more frequent with G + B: 41/52 (79%) pts were MRD negative at MI vs 17/36 (47%) in the B arm (p = 0.0029). At EOI, MRD responses further increased: 54/63 (86%) pts receiving G + B achieved MRD negativity in PB and/or BM vs 30/55 (55%) in the B arm (p = 0.0002) (Table ). Pts with complete/ partial response who were MRD negative at EOI had improved PFS and OS vs MRD-positive pts; hazard ratios (adjusted for treatment): PFS, 0.33 (95% CI 0.19-0.56, p Conclusion(s): MRD status at EOI was a sensitive marker of treatment efficacy, demonstrating that adding G to B-based treatment significantly contributes to the speed and depth of response. MRD-negative pts after G + B appeared to benefit from G maintenance, which potentially preserved MRD negativity and helped to control lymphoma regrowth. (Table Presented).