Efficacy and safety of obinutuzumab versus rituximab in patients with FL: GALLIUM trial

Rituximab-based chemotherapy has been shown to improve outcomes in patients with follicular lymphoma (FL). However, most patients relapse and overall survival is poor. Obinutuzumab, an anti-CD20 monoclonal antibody, has a greater antibody dependent cytotoxicity and B-cell killing effect than rituximab.¹ The phase III GALLIUM trial (NCT01332968) assessed the efficacy and safety of obinutuzumab- versus rituximab-based immunochemotherapy in patients with previously untreated, advanced-stage indolent non-Hodgkin's lymphoma (iNHL), including follicular lymphoma (FL) or marginal zone lymphoma (MZL).

The Lymphoma Hub has previously reported an update on the GALLIUM trial. The final analysis of the GALLIUM trial was recently published by Townsend et al.¹ in HemaSphere. We are pleased to summarize the key findings here.

Study design¹

GALLIUM is an international multi-center, open-label randomized phase III trial of obinutuzumab- versus rituximab-based immunochemotherapy.

Patients were randomized 1:1 to receive either obinutuzumab or rituximab, plus chemotherapy (Figure 1). Maintenance treatment was given to patients with a complete or partial response for 2 years or until disease progression or withdrawal. Patients with stable disease at the end of induction did not receive maintenance and were observed until disease progression or withdrawal.

ECOG, Eastern Cooperative Oncology Group; FL, follicular lymphoma; iNHL, indolent non-Hodgkin lymphoma; MZL, marginal zone lymphoma.
*Adapted from Townsend, et al.^1
†FL grade 1–3a or splenic, nodal, or extranodal MZL.
^‡Stage III/IV, or stage II with bulk ≥7cm.

Results¹

A total of 1,397 patients were included, and the baseline characteristics were well balanced across both treatment arms (Table 1).

Table 1. Baseline characteristics*

CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisolone; CVP, cyclophosphamide, vincristine, and prednisolone; FL, follicular lymphoma; FLIPI, Follicular Lymphoma International Prognostic Index; MZL, marginal zone lymphoma. *Adapted from Townsend, et al.1
Characteristic, % (unless otherwise stated)	FL cohort (n = 1202)		MZL cohort (n = 195)
	Obinutuzumab (n = 601)	Rituximab (n = 601)	Obinutuzumab (n = 99)	Rituximab (n = 96)
Median age (range), years	60 (26–88)	58 (23–85)	63 (36–85)	62 (29–88)
MZL subtype
Nodal			36.4	31.3
Extranodal			24.2	38.5
Splenic			39.4	30.2
Ann Arbor stage at diagnosis
I	1.7	1.3	6.1	0
II	6.8	7.3	1.0	3.1
III	34.6	34.8	10.1	14.6
IV	56.4	55.9	82.8	82.3
Missing	0.5	0.7	0	0
FLIPI risk score
Low	21.3	20.8
Intermediate	37.3	37.1
High	41.4	42.1
B symptoms	33.4	34.3	41.4	33.3
Chemotherapy regimen
Bendamustine	57.4	56.7	73.7	68.8
CHOP	32.4	33.8	14.1	18.8
CVP	10.1	9.5	12.1	12.5

Efficacy

• At a median follow-up of 7.9 years, progression-free survival (PFS) and time-to-next lymphoma treatment were greatly improved in with obinutuzumab compared with rituximab in the FL cohort (Figure 2).
• The 7-year event-free survival was also improved in the obinutuzumab versus rituximab arm.

EFS, event-free survival; FL, follicular lymphoma; NLT, next lymphoma treatment; OS, overall survival; PFS, progression-free survival.
*Data from Townsend, et al.^1
†Patients who were alive and had not started the NLT at Year 7.

• In a pre-planned subgroup analysis, a PFS benefit was observed with obinutuzumab versus rituximab in patients with an intermediate-to-high (2–5) Follicular Lymphoma International Prognostic Index (FLIPI) score; the 7-year PFS rate was 62.9% versus 51.8%, respectively (hazard ratio [HR], 0.70; p < 0.001).

• Complete metabolic response (CMR) was achieved by 78.8% and 72.5% of patients in the obinutuzumab and rituximab arms, respectively.
  • Both PFS and OS were higher in patients achieving CMR versus no CMR, irrespective of the treatment received (Figure 3).
  • In patients achieving a CMR, the 7-year PFS rate was greater in the obinutuzumab versus rituximab arm (62.5% versus 51.4%, respectively).
  • In patients achieving a CMR, the 7-year OS rate was similar between treatment arms, at 90.6% in the obinutuzumab arm versus 89.8% in the rituximab arm.

In the MZL cohort, the 7-year PFS rate in the MZL cohort was 59.8% in the obinutuzumab arm versus 52.2% in the rituximab arm.

CMR, complete molecular response; FL, follicular lymphoma; OS, overall survival; PFS, progression-free survival.
*Data from Townsend, et al.¹

Safety

The most common adverse events in the FL cohort were infusion-related reaction, neutropenia, and nausea (Figure 4). In total, 48.9% of patients in the obinutuzumab arm and 43.4% of patients in the rituximab arm experienced a serious adverse event. Two deaths due to adverse events were reported in the obinutuzumab arm and seven in the rituximab arm. Most fatal adverse events occurred in patients who received bendamustine, with no difference between treatment arms (5.9% of patients who received obinutuzumab plus bendamustine versus 6.2% of patients who received rituximab plus bendamustine).

*Adapted from Townsend, et al.¹

Conclusion¹

The results of the phase III GALLIUM trial demonstrated the longer-term improvement in PFS and time-to-next lymphoma treatment of obinutuzumab-based immunochemotherapy over rituximab-based immunochemotherapy in patients with previously untreated FL. Overall, AEs were manageable with no new safety signals reported.