Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study

Emmanuel Bachy (1, 2) , Roch Houot (3, 4) , Pierre Feugier (5) , Krimo Bouabdallah (6) , Reda Bouabdallah (7) , Emmanuelle Nicolas Virelizier (8) , Marie Maerevoet (9) , Christophe Fruchart (10) , Sylvia Snauwaert (11) , Steven Le Gouill (12, 13, 14, 15, 16) , Jean-Pierre Marolleau (17, 18) , Lysiane Molina (19) , Cecile Molucon-Chabrot (20) , Catherine Thieblemont (21, 22) , Herve Tilly (23, 24) , Fontanet Bijou (25) , Corinne Haioun (26, 27) , Eric van Den Neste (28) , Bettina Fabiani (29) , Michel Meignan (26, 30) , Guillaume Cartron (31) , Gilles Salles (32) , Olivier Casasnovas (33) , Franck Morschhauser (34)

1 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
2 UCBL - Université Claude Bernard Lyon 1
3 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
4 MOBIDIC - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer
5 Filo - French Innovative Leukemia Organization
6 CHU Bordeaux [Bordeaux]
7 Institut Paoli-Calmettes
8 Centre Léon Bérard [Lyon]
9 Institut Jules Bordet [Bruxelles]
10 CH Dunkerque
11 Department of ENT surgery, AZ Sint Jan Brugge Oostende
12 Service d'Hématologie Biologique [CHU Nantes]
13 i-Site NexT - L’Héma-NexT [UNIV Nantes]
14 CNRS GDR 3697 Micronit - Microenvironnement des niches tumorales
15 CRCI2NA - Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
16 CHU Nantes - Centre hospitalier universitaire de Nantes
17 CHU Amiens-Picardie
18 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
19 CHU Grenoble
20 Service d’Hématologie Biologique [CHU Clermont-Ferrand]
21 AP-HP - Hopital Saint-Louis [AP-HP]
22 OncokappaB (URP_7324) - NF-kappaB, Différenciation et Cancer
23 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
24 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
25 Institut Bergonié [Bordeaux]
26 Hôpital Henri Mondor
27 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
28 Cliniques Universitaires Saint-Luc [Bruxelles]
29 Service de neurophysiologie [CHU Saint-Antoine]
30 LYSA-IM - LYSA Imaging (Créteil)
31 CHU Montpellier
32 Weill Medical College of Cornell University [New York]
33 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
34 CHU Lille

Obinutuzumab and lenalidomide (referred to as the GALEN combination) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥18 years had an Eastern Cooperative Oncology Group performance status ≤2 and high-tumor burden, grade 1 to 3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8, 15, and 22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/d, days 1-21, cycle 1; days 2-22, cycles 2-6) for six 28-day cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary end point was complete response rate (CRR) after induction per the 1999 International Working Group criteria. From October 2015 to February 2017, a total of 100 patients were enrolled. CRR after induction was 47%, and the overall response rate (ORR) was 92%. Post hoc analyses per the 2014 Lugano classification, including patients with missing bone marrow assessments, identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and an ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free survival and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any grade; 47% grade ≥3). Only 2% of patients presented with febrile neutropenia; others were mainly grade ≤2. No other specific grade ≥3 toxicity occurred at a frequency >3%. Overall, these results showed promising clinical efficacy for the chemotherapy-free GALEN backbone in previously untreated patients with high tumor burden FL. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered at clinicaltrials.gov as #NCT01582776.

Domaines: Sciences du Vivant [q-bio]; Sciences du Vivant [q-bio]; Cancer

Emmanuel Bachy, Roch Houot, Pierre Feugier, Krimo Bouabdallah, Reda Bouabdallah, et al.. Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study. Blood, 2022, 139 (15), pp.2338-2346. ⟨10.1182/blood.2021013526⟩. ⟨hal-03679319⟩