Health-related quality of life in the phase III GALLIUM study of obinutuzumab- or rituximab-based chemotherapy in patients with previously untreated advanced follicular lymphoma

Andrew Davies, Peter Trask, Judit Demeter, Axel Florschütz, Mathias Hänel, Tomohiro Kinoshita, Ruth Pettengell, Hang Quach, Stephen Robinson, Shalal Sadullah, Juan-Manuel Sancho, Miklos Udvardy, Mathias Witzens-Harig, Andrea Knapp, Wenxin Liu, Andrew Davies, Peter Trask, Judit Demeter, Axel Florschütz, Mathias Hänel, Tomohiro Kinoshita, Ruth Pettengell, Hang Quach, Stephen Robinson, Shalal Sadullah, Juan-Manuel Sancho, Miklos Udvardy, Mathias Witzens-Harig, Andrea Knapp, Wenxin Liu

Abstract

Health-related quality of life was a secondary endpoint in the phase III GALLIUM study in previously untreated patients with follicular lymphoma who were treated with rituximab- or obinutuzumab-chemotherapy. Patients were randomized 1:1 to receive induction therapy with obinutuzumab- or rituximab-chemotherapy and maintenance in responders. Health-related quality of life was assessed using the Functional Assessment of Cancer Treatment-Lymphoma questionnaire, incorporating well-being and lymphoma-specific subscales. Assessments were performed at baseline, and during induction, maintenance, and follow-up (maximum 84 months). Clinically meaningful responses were defined by minimally important difference values. Of 1202 randomized patients (median follow-up 57.4 months), 557/601 (92.7%; obinutuzumab-chemotherapy) and 548/601 (91.2%; rituximab-chemotherapy) completed all Functional Assessment of Cancer Treatment-Lymphoma scales at baseline. Mean baseline health-related quality of life scores were similar between both arms, with all patients having some functional impairment and lymphoma symptoms. Over the course of treatment, mean health-related quality of life remained similar in both arms. Equal proportions of patients in both arms achieved minimally important difference by the Functional Assessment of Cancer Treatment-Lymphoma lymphoma-specific subscale and summary scales throughout induction, maintenance, and follow-up. On each summary scale, ~ 50% of patients in each arm achieved minimally important difference by maintenance month 2. In GALLIUM, similar improvements in health-related quality of life were seen with obinutuzumab- and rituximab-chemotherapy, suggesting that both treatments reduced lymphoma-related symptoms, and treatment-related side effects did not abrogate these improvements in well-being. ClinicalTrials.gov identifier: NCT01332968.

Keywords: Follicular lymphoma; Indolent non-Hodgkin lymphoma; Obinutuzumab; Quality of life; Rituximab.

Conflict of interest statement

AD, research funding (Celgene), research support (F. Hoffmann-La Roche Ltd., Gilead/Kite, Takeda, GSK, Karyopharm, Pfizer, Acerta Pharma), advisory board participation (Celgene, F. Hoffmann-La Roche Ltd., Gilead/Kite,Takeda, Karyopharm, Acerta Pharma), honoraria (Celgene, F. Hoffmann-La Roche Ltd., Gilead/Kite, Takeda, Janssen, Pfizer, Acerta Pharma), and travel to scientific conferences (Takeda). PT, employment (Genentech Inc). HQ, research funding (Celgene, Amgen) and advisory board participation (Celgene, Amgen, GSK, Karyopharm, Takeda). SR, advisory board participation, speaker fees, and honoraria (F. Hoffmann-La Roche Ltd., Takeda, Novartis, Gilead, Sandoz). TK, research funding (Chugai, Takeda, Solaisia, Ono, Gilead, MSD, Zenyaku) and personal fees (Chugai, Ono, Gilead, MSD, Zenyaku, Bristol, Kyowa Kirin, Eisai, Janssen). RP, personal fees (CTI Life Sciences Ltd., Roche, Servier, Takeda) and advisory board participation (CTI Life Sciences Ltd., G1 Therapeutics Inc., Immune Design, Pfizer, F. Hoffmann-La Roche Ltd., Servier, Takeda, TEVA). JMS, honoraria (F. Hoffmann-La Roche Ltd., Gilead, Janssen, Celgene, Novartis, Mundipharma, Kern-Pharma, Sanofi) and advisory board participation (F. Hoffmann-La Roche Ltd., Gilead, Janssen, Celgene, Celltrion, Sandoz, Bristol-Myers Sqibb). MH, honoraria (Novartis, Amgen, F. Hoffmann-La Roche Ltd) and advisory board participation (Celgene, Takeda). SS, advisory board participation (Takeda, NAPP Pharmaceuticals) and personal fees (Janssen, Novartis). AK and WL, employment (F. Hoffmann-La Roche Ltd). The remaining authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
FACT-Lym questionnaire completion data for R-chemo vs. G-chemo. The table below the graph shows the number of patients still receiving treatment who completed all FACT-Lym scales at the specified time point. C, cycle; chemo, chemotherapy; D, day; EOI, end of induction; EOM, end of maintenance; FACT-Lym, Functional Assessment of Cancer Treatment-Lymphoma; FU, follow-up; G, obinutuzumab; Maint, maintenance; R, rituximab
Fig. 2
Fig. 2
Mean change from baseline in FACT-G PWB, FWB, EWB, and SWB, by treatment arm. a PWB, b FWB, c EWB, and d SWB. *Changes of 2–3 points are considered meaningful on the PWB, FWB, and EWB scales. A meaningful change has not yet been defined for the SWB scale. The number of patients still receiving treatment who completed the FACT-G questionnaire at the specified time point is specified below the graph. C, cycle; chemo, chemotherapy; D, day; EOI, end of induction; EOM, end of maintenance; EWB, emotional well-being; FACT-G, Functional Assessment of Cancer Treatment-General; FU, follow-up; FWB, functional well-being; G, obinutuzumab; Maint, maintenance; MID, minimally important difference; PWB, physical well-being; R, rituximab; SWB, social/family well-being
Fig. 3
Fig. 3
Mean change from baseline in FACT-Lym LYMS, TOI, and TOT scores, by treatment arm. a LYMS, b TOI, and c TOT. The number of patients still receiving treatment who completed the FACT-Lym questionnaire at the specified time point is specified below the graph. C, cycle; chemo, chemotherapy; D, day; EOI, end of induction; EOM, end of maintenance; FACT-Lym, Functional Assessment of Cancer Treatment-Lymphoma; FU, follow-up; G, obinutuzumab; LYMS, lymphoma-specific; Maint, maintenance; MID, minimally important difference; R, rituximab; TOI, trial outcome index; TOT, total
Fig. 4
Fig. 4
Proportion of patients with FL achieving MID on FACT-Lym LYMS score (≥ 3), TOI score (≥ 6), and TOT score (≥ 7). a LYMS (≥ 3), b TOI (≥ 6), and c TOT (≥ 7) score. The number of patients still receiving treatment who achieved MID at the specified time point is specified below the graph. C, cycle; chemo, chemotherapy; D, day; EOI, end of induction; EOM, end of maintenance; FACT-Lym, Functional Assessment of Cancer Treatment-Lymphoma; FL, follicular lymphoma; FU, follow-up; G, obinutuzumab; LYMS, lymphoma-specific; Maint, maintenance; MID, minimally important difference; R, rituximab; TOI, trial outcome index; TOT, total

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