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SUB-CUTANEOUS RITUXIMAB INDUCTION FOLLOWED BY SHORT RITUXIMAB MAINTENANCE IMPROVES PFS IN PATIENTS WITH LOW-TUMOR BURDEN FOLLICULAR LYMPHOMA. FINAL RESULTS OF FLIRT PHASE III TRIAL, A LYSA STUDY.
Author(s): ,
Guillaume Cartron, MD, PhD
Affiliations:
Haematology,CHU de Montpellier,MONTPELLIER Cedex 5,France;Haematology,CHU de Montpellier,MONTPELLIER Cedex 5,Frankreich;Haematology,CHU de Montpellier,MONTPELLIER Cedex 5,Francia;Haematology,CHU de Montpellier,MONTPELLIER Cedex 5,France;Haematology,CHU de Montpellier,MONTPELLIER Cedex 5,Francia;Haematology,CHU de Montpellier,MONTPELLIER Cedex 5,Frankrijk;Haematology,CHU de Montpellier,MONTPELLIER
,
Emmanuel Bachy, MD, PhD
Affiliations:
CHU Lyon Sud,Pierre Benite,France;CHU Lyon Sud,Pierre Benite,Frankreich;CHU Lyon Sud,Pierre Benite,Francia;CHU Lyon Sud,Pierre Benite,France;CHU Lyon Sud,Pierre Benite,Francia;CHU Lyon Sud,Pierre Benite,Frankrijk;CHU Lyon Sud,Pierre Benite,França;CHU Lyon Sud,Pierre Benite,Франция ;CHU Lyon Sud,Pierre Benite,Frankrike
,
Hervé Tilly, MD
Affiliations:
Centre Henri Becquerel,Rouen,France;Centre Henri Becquerel,Rouen,Frankreich;Centre Henri Becquerel,Rouen,Francia;Centre Henri Becquerel,Rouen,France;Centre Henri Becquerel,Rouen,Francia;Centre Henri Becquerel,Rouen,Frankrijk;Centre Henri Becquerel,Rouen,França;Centre Henri Becquerel,Rouen,Франция ;Centre Henri Becquerel,Rouen,Frankrike
,
Nicolas Daguindau,MD
Affiliations:
Centre Hospitalier Annecy-Genevois - Site d'Annecy,Pringy Cedex,France;Centre Hospitalier Annecy-Genevois - Site d'Annecy,Pringy Cedex,Frankreich;Centre Hospitalier Annecy-Genevois - Site d'Annecy,Pringy Cedex,Francia;Centre Hospitalier Annecy-Genevois - Site d'Annecy,Pringy Cedex,France;Centre Hospitalier Annecy-Genevois - Site d'Annecy,Pringy Cedex,Francia;Centre Hospitalier Annecy-Genevois - Si
,
Gian-Matteo Pica, MD
Affiliations:
CH de Chambéry,Chambéry,France;CH de Chambéry,Chambéry,Frankreich;CH de Chambéry,Chambéry,Francia;CH de Chambéry,Chambéry,France;CH de Chambéry,Chambéry,Francia;CH de Chambéry,Chambéry,Frankrijk;CH de Chambéry,Chambéry,França;CH de Chambéry,Chambéry,Франция ;CH de Chambéry,Chambéry,Frankrike
,
Fontanet Bijou, MD
Affiliations:
Institut Bergonié,Bordeaux,France;Institut Bergonié,Bordeaux,Frankreich;Institut Bergonié,Bordeaux,Francia;Institut Bergonié,Bordeaux,France;Institut Bergonié,Bordeaux,Francia;Institut Bergonié,Bordeaux,Frankrijk;Institut Bergonié,Bordeaux,França;Institut Bergonié,Bordeaux,Франция ;Institut Bergonié,Bordeaux,Frankrike
,
Christiane Mounier, MD
Affiliations:
Institut de Cancérologie Lucien Neuwirth,St-Priest-en-Jarez,France;Institut de Cancérologie Lucien Neuwirth,St-Priest-en-Jarez,Frankreich;Institut de Cancérologie Lucien Neuwirth,St-Priest-en-Jarez,Francia;Institut de Cancérologie Lucien Neuwirth,St-Priest-en-Jarez,France;Institut de Cancérologie Lucien Neuwirth,St-Priest-en-Jarez,Francia;Institut de Cancérologie Lucien Neuwirth,St-Priest-en-Jarez
,
Aline, MD Clavert, MD
Affiliations:
CHU Angers,Angers,France;CHU Angers,Angers,Frankreich;CHU Angers,Angers,Francia;CHU Angers,Angers,France;CHU Angers,Angers,Francia;CHU Angers,Angers,Frankrijk;CHU Angers,Angers,França;CHU Angers,Angers,Франция ;CHU Angers,Angers,Frankrike
,
Gandhi Laurent Damaj, MD, PhD
Affiliations:
CHU Côte de Nacre,Caen,France;CHU Côte de Nacre,Caen,Frankreich;CHU Côte de Nacre,Caen,Francia;CHU Côte de Nacre,Caen,France;CHU Côte de Nacre,Caen,Francia;CHU Côte de Nacre,Caen,Frankrijk;CHU Côte de Nacre,Caen,França;CHU Côte de Nacre,Caen,Франция ;CHU Côte de Nacre,Caen,Frankrike
,
Borhane Slama, MD
Affiliations:
CH d'Avignon - Hôpital Henri Duffaut,Avignon,France;CH d'Avignon - Hôpital Henri Duffaut,Avignon,Frankreich;CH d'Avignon - Hôpital Henri Duffaut,Avignon,Francia;CH d'Avignon - Hôpital Henri Duffaut,Avignon,France;CH d'Avignon - Hôpital Henri Duffaut,Avignon,Francia;CH d'Avignon - Hôpital Henri Duffaut,Avignon,Frankrijk;CH d'Avignon - Hôpital Henri Duffaut,Avignon,França;CH d'Avignon - Hôpital Henr
,
Olivier Casasnovas, MD
Affiliations:
CHU Dijon - Hôpital d'Enfants,Dijon,France;CHU Dijon - Hôpital d'Enfants,Dijon,Frankreich;CHU Dijon - Hôpital d'Enfants,Dijon,Francia;CHU Dijon - Hôpital d'Enfants,Dijon,France;CHU Dijon - Hôpital d'Enfants,Dijon,Francia;CHU Dijon - Hôpital d'Enfants,Dijon,Frankrijk;CHU Dijon - Hôpital d'Enfants,Dijon,França;CHU Dijon - Hôpital d'Enfants,Dijon,Франция ;CHU Dijon - Hôpital d'Enfants,Dijon,Frankrike
,
Roch Houot, MD, PhD
Affiliations:
CHU Rennes,Rennes,France;CHU Rennes,Rennes,Frankreich;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,France;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,Frankrijk;CHU Rennes,Rennes,França;CHU Rennes,Rennes,Франция ;CHU Rennes,Rennes,Frankrike
,
Krimo Bouabdallah, MD
Affiliations:
CHU Bordeaux,Bordeaux,France;CHU Bordeaux,Bordeaux,Frankreich;CHU Bordeaux,Bordeaux,Francia;CHU Bordeaux,Bordeaux,France;CHU Bordeaux,Bordeaux,Francia;CHU Bordeaux,Bordeaux,Frankrijk;CHU Bordeaux,Bordeaux,França;CHU Bordeaux,Bordeaux,Франция ;CHU Bordeaux,Bordeaux,Frankrike
,
David Sibon, MD, PhD
Affiliations:
Hôpital Necker,Paris,France;Hôpital Necker,Paris,Frankreich;Hôpital Necker,Paris,Francia;Hôpital Necker,Paris,France;Hôpital Necker,Paris,Francia;Hôpital Necker,Paris,Frankrijk;Hôpital Necker,Paris,França;Hôpital Necker,Paris,Франция ;Hôpital Necker,Paris,Frankrike
,
Olivier Fitoussi, MD
Affiliations:
Polyclinique Bordeaux Nord Aquitaine,Bordeaux,France;Polyclinique Bordeaux Nord Aquitaine,Bordeaux,Frankreich;Polyclinique Bordeaux Nord Aquitaine,Bordeaux,Francia;Polyclinique Bordeaux Nord Aquitaine,Bordeaux,France;Polyclinique Bordeaux Nord Aquitaine,Bordeaux,Francia;Polyclinique Bordeaux Nord Aquitaine,Bordeaux,Frankrijk;Polyclinique Bordeaux Nord Aquitaine,Bordeaux,França;Polyclinique Bordeau
,
Nadine Morineau, MD
Affiliations:
CH Départemental Vendée,La Roche sur Yon,France;CH Départemental Vendée,La Roche sur Yon,Frankreich;CH Départemental Vendée,La Roche sur Yon,Francia;CH Départemental Vendée,La Roche sur Yon,France;CH Départemental Vendée,La Roche sur Yon,Francia;CH Départemental Vendée,La Roche sur Yon,Frankrijk;CH Départemental Vendée,La Roche sur Yon,França;CH Départemental Vendée,La Roche sur Yon,Франция ;CH Dé
,
Charles Herbaux, MD, PhD
Affiliations:
CHU Montpellier,Montpellier,France;CHU Montpellier,Montpellier,Frankreich;CHU Montpellier,Montpellier,Francia;CHU Montpellier,Montpellier,France;CHU Montpellier,Montpellier,Francia;CHU Montpellier,Montpellier,Frankrijk;CHU Montpellier,Montpellier,França;CHU Montpellier,Montpellier,Франция ;CHU Montpellier,Montpellier,Frankrike
,
Thomas Gastinne, MD
Affiliations:
CHU de Nantes - Hôtel Dieu,Nantes,France;CHU de Nantes - Hôtel Dieu,Nantes,Frankreich;CHU de Nantes - Hôtel Dieu,Nantes,Francia;CHU de Nantes - Hôtel Dieu,Nantes,France;CHU de Nantes - Hôtel Dieu,Nantes,Francia;CHU de Nantes - Hôtel Dieu,Nantes,Frankrijk;CHU de Nantes - Hôtel Dieu,Nantes,França;CHU de Nantes - Hôtel Dieu,Nantes,Франция ;CHU de Nantes - Hôtel Dieu,Nantes,Frankrike
,
Luc- Matthieu Fornecker, MD
Affiliations:
Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre,Strasbourg,France;Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre,Strasbourg,Frankreich;Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre,Strasbourg,Francia;Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre,Strasbourg,France;Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre,Strasbou
,
Corinne Haioun, MD, PhD
Affiliations:
Hôpital Henri Mondor,Créteil,France;Hôpital Henri Mondor,Créteil,Frankreich;Hôpital Henri Mondor,Créteil,Francia;Hôpital Henri Mondor,Créteil,France;Hôpital Henri Mondor,Créteil,Francia;Hôpital Henri Mondor,Créteil,Frankrijk;Hôpital Henri Mondor,Créteil,França;Hôpital Henri Mondor,Créteil,Франция ;Hôpital Henri Mondor,Créteil,Frankrike
,
Vincent Launay, MD
Affiliations:
CH de Saint-Brieuc - Hôpital Yves Le Foll,Saint- Brieuc,France;CH de Saint-Brieuc - Hôpital Yves Le Foll,Saint- Brieuc,Frankreich;CH de Saint-Brieuc - Hôpital Yves Le Foll,Saint- Brieuc,Francia;CH de Saint-Brieuc - Hôpital Yves Le Foll,Saint- Brieuc,France;CH de Saint-Brieuc - Hôpital Yves Le Foll,Saint- Brieuc,Francia;CH de Saint-Brieuc - Hôpital Yves Le Foll,Saint- Brieuc,Frankrijk;CH de Saint-B
,
Carla Araujo, MD
Affiliations:
Centre Hospitalier de la Côte Basque - Hôpital de Bayonne,Bayonne,France;Centre Hospitalier de la Côte Basque - Hôpital de Bayonne,Bayonne,Frankreich;Centre Hospitalier de la Côte Basque - Hôpital de Bayonne,Bayonne,Francia;Centre Hospitalier de la Côte Basque - Hôpital de Bayonne,Bayonne,France;Centre Hospitalier de la Côte Basque - Hôpital de Bayonne,Bayonne,Francia;Centre Hospitalier de la Côte
,
Omar Benbrahim, MD
Affiliations:
CHR de la Source,Orléans,France;CHR de la Source,Orléans,Frankreich;CHR de la Source,Orléans,Francia;CHR de la Source,Orléans,France;CHR de la Source,Orléans,Francia;CHR de la Source,Orléans,Frankrijk;CHR de la Source,Orléans,França;CHR de la Source,Orléans,Франция ;CHR de la Source,Orléans,Frankrike
,
Laurence Sanhes, MD
Affiliations:
Hôpital Saint Jean,Perpignan,France;Hôpital Saint Jean,Perpignan,Frankreich;Hôpital Saint Jean,Perpignan,Francia;Hôpital Saint Jean,Perpignan,France;Hôpital Saint Jean,Perpignan,Francia;Hôpital Saint Jean,Perpignan,Frankrijk;Hôpital Saint Jean,Perpignan,França;Hôpital Saint Jean,Perpignan,Франция ;Hôpital Saint Jean,Perpignan,Frankrike
,
Remy Gressin, MD
Affiliations:
CHU de Grenoble - Hôpital Albert Michallon,Grenoble,France;CHU de Grenoble - Hôpital Albert Michallon,Grenoble,Frankreich;CHU de Grenoble - Hôpital Albert Michallon,Grenoble,Francia;CHU de Grenoble - Hôpital Albert Michallon,Grenoble,France;CHU de Grenoble - Hôpital Albert Michallon,Grenoble,Francia;CHU de Grenoble - Hôpital Albert Michallon,Grenoble,Frankrijk;CHU de Grenoble - Hôpital Albert Mich
,
Hugo Gonzalez, MD
Affiliations:
CH René Dubos,Pontoise,France;CH René Dubos,Pontoise,Frankreich;CH René Dubos,Pontoise,Francia;CH René Dubos,Pontoise,France;CH René Dubos,Pontoise,Francia;CH René Dubos,Pontoise,Frankrijk;CH René Dubos,Pontoise,França;CH René Dubos,Pontoise,Франция ;CH René Dubos,Pontoise,Frankrike
,
Franck Morschhauser, MD, PhD
Affiliations:
CHRU de Lille - Hôpital Claude Hurriez,Lille,France;CHRU de Lille - Hôpital Claude Hurriez,Lille,Frankreich;CHRU de Lille - Hôpital Claude Hurriez,Lille,Francia;CHRU de Lille - Hôpital Claude Hurriez,Lille,France;CHRU de Lille - Hôpital Claude Hurriez,Lille,Francia;CHRU de Lille - Hôpital Claude Hurriez,Lille,Frankrijk;CHRU de Lille - Hôpital Claude Hurriez,Lille,França;CHRU de Lille - Hôpital Cla
,
Luc Xerri, MD, PhD
Affiliations:
Departement de bio-pathologie,Institut Paoli Calmette,Marseille,France;Departement de bio-pathologie,Institut Paoli Calmette,Marseille,Frankreich;Departement de bio-pathologie,Institut Paoli Calmette,Marseille,Francia;Departement de bio-pathologie,Institut Paoli Calmette,Marseille,France;Departement de bio-pathologie,Institut Paoli Calmette,Marseille,Francia;Departement de bio-pathologie,Institut
,
Karin Tarte, PhD
Affiliations:
CHU Rennes,Rennes,France;CHU Rennes,Rennes,Frankreich;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,France;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,Frankrijk;CHU Rennes,Rennes,França;CHU Rennes,Rennes,Франция ;CHU Rennes,Rennes,Frankrike
Delphine Pranger, MD
Affiliations:
GHdC,Charleroi,Belgique;GHdC,Charleroi,Belgien;GHdC,Charleroi,Belgio;GHdC,Charleroi,Belgium;GHdC,Charleroi,Bélgica;GHdC,Charleroi,België;GHdC,Charleroi,Bélgica;GHdC,Charleroi,Belgium;GHdC,Charleroi,Belgien
(Abstract release date: 05/12/22) EHA Library. Cartron G. 06/10/22; 357993; P1133
Dr. Guillaume Cartron
Dr. Guillaume Cartron
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1133

Type: Poster presentation

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background

In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival (PFS) when compared with observation. RESORT study (Kahl et al. 2014) clearly showed that Rituximab (R) retreatment strategy provided similar time to treatment failure that maintenance strategy with less rituximab use. 

Aims
It is not known whether short MR using sub-cutaneous (sc) route could improve PFS while reducing R infusions.

Methods
Patients with the diagnosis of low-tumor burden FL (GELF criteria) within the last 4 months before signing informed consent were randomly assigned to either Iv-Arm : 4-weekly iv infusions of R 375 mg/m2 or Sc-Arm: one iv infusion of R (D1, 375 mg/m2) followed by 3 sc infusions of R (1400 mg, on days 8, 15 and 22) followed by Rsc maintenance on months (M) 3, 5, 7 and 9. The primary endpoint was PFS and secondary endpoints included safety, response rates (M3, M12), duration of response (DOR), time to next anti-lymphoma treatment (TTNTL) and overall survival (OS).

Results

A total of 202 patients were included, 102 in Iv-Arm and 100 in Sc-Arm and constitute the intent to treat population. The median uses of R were 4 infusions (range: 1-4, Iv-Arm) and 8 infusions (range: 2-8, Sc-Arm). With a median follow-up of 50.2 months (95% CI: 48.3-54.5), 4‐year PFS was 41.2% (95% CI: 30.6%; 51.6%) in Iv-Arm and 58.1% (95% CI: 47.5%; 67.4%) in Sc-Arm. Median PFS was then 36.1 months (95% IC: 23.9-52.6) in Iv-Arm and 73.8 months (95% CI: 39.4-NA) in Sc-Arm (Fig 1.) (HR: 0.58; 95% CI: 0.39-0.87; P = 0.0076). Patients with at least one AE grade ≥ 3 were 8 (7.8%) and 12 (12.4%) in Iv-Arm and Sc-Arm, respectively. According to Cheson criteria, ORR at M3 were: 83% and 80% including 38% and 29% of CR/CRu, in Iv-Arm and Sc-Arm, respectively. According to Lugano criteria, 36.3% (Iv-Arm; 95% CI: 27.0%. 46.4%) and 59.0% (Sc-Arm; 95% CI: 48.7%; 68.7%) were in CMR at M12. The median DOR was 32.7 months (95% IC: 20.6-49.7) and 70.8 months (36.4-NR) (HR: 0.56; 95% IC: 0.37-0.84) in Iv-Arm and Sc-Arm, respectively. 4-year TTNLT was 54% (95% CI: 42.9%; 63.8%) in Iv-Arm and 61.8% (95% CI: 50.8.6%; 71.0%) in Sc-Arm (HR: 0.81, 95% IC: 0.53-1.24). 4-year TTNLT chemotherapy was 60.8 % (95% CI: 49.6%; 70.3%) in Iv-Arm and 71.4% (95% CI: 60.7%; 79.8%) in Sc-arm (HR: 0.69, 95% IC: 0.42-1.12) (Fig 2.). OS was not different according to treatment arm, 4-year OS was 95.0% (95% CI: 88.5%; 97.9%) in Iv-Arm and 96.7% (95% CI: 89.9%; 98.9%) in Sc-Arm.

Conclusion
This phase III study met its primary endpoint and demonstrated that Rsc induction followed by a short MRsc improves PFS of patients with low-tumor burden. MRsc did not however improved TTNLT. R in low-tumor burden FL allowed to avoid cytotoxic use in most patients 6 years after treatment initiation.

Keyword(s): Follicular lymphoma, Rituximab, Subcutaneous

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1133

Type: Poster presentation

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background

In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival (PFS) when compared with observation. RESORT study (Kahl et al. 2014) clearly showed that Rituximab (R) retreatment strategy provided similar time to treatment failure that maintenance strategy with less rituximab use. 

Aims
It is not known whether short MR using sub-cutaneous (sc) route could improve PFS while reducing R infusions.

Methods
Patients with the diagnosis of low-tumor burden FL (GELF criteria) within the last 4 months before signing informed consent were randomly assigned to either Iv-Arm : 4-weekly iv infusions of R 375 mg/m2 or Sc-Arm: one iv infusion of R (D1, 375 mg/m2) followed by 3 sc infusions of R (1400 mg, on days 8, 15 and 22) followed by Rsc maintenance on months (M) 3, 5, 7 and 9. The primary endpoint was PFS and secondary endpoints included safety, response rates (M3, M12), duration of response (DOR), time to next anti-lymphoma treatment (TTNTL) and overall survival (OS).

Results

A total of 202 patients were included, 102 in Iv-Arm and 100 in Sc-Arm and constitute the intent to treat population. The median uses of R were 4 infusions (range: 1-4, Iv-Arm) and 8 infusions (range: 2-8, Sc-Arm). With a median follow-up of 50.2 months (95% CI: 48.3-54.5), 4‐year PFS was 41.2% (95% CI: 30.6%; 51.6%) in Iv-Arm and 58.1% (95% CI: 47.5%; 67.4%) in Sc-Arm. Median PFS was then 36.1 months (95% IC: 23.9-52.6) in Iv-Arm and 73.8 months (95% CI: 39.4-NA) in Sc-Arm (Fig 1.) (HR: 0.58; 95% CI: 0.39-0.87; P = 0.0076). Patients with at least one AE grade ≥ 3 were 8 (7.8%) and 12 (12.4%) in Iv-Arm and Sc-Arm, respectively. According to Cheson criteria, ORR at M3 were: 83% and 80% including 38% and 29% of CR/CRu, in Iv-Arm and Sc-Arm, respectively. According to Lugano criteria, 36.3% (Iv-Arm; 95% CI: 27.0%. 46.4%) and 59.0% (Sc-Arm; 95% CI: 48.7%; 68.7%) were in CMR at M12. The median DOR was 32.7 months (95% IC: 20.6-49.7) and 70.8 months (36.4-NR) (HR: 0.56; 95% IC: 0.37-0.84) in Iv-Arm and Sc-Arm, respectively. 4-year TTNLT was 54% (95% CI: 42.9%; 63.8%) in Iv-Arm and 61.8% (95% CI: 50.8.6%; 71.0%) in Sc-Arm (HR: 0.81, 95% IC: 0.53-1.24). 4-year TTNLT chemotherapy was 60.8 % (95% CI: 49.6%; 70.3%) in Iv-Arm and 71.4% (95% CI: 60.7%; 79.8%) in Sc-arm (HR: 0.69, 95% IC: 0.42-1.12) (Fig 2.). OS was not different according to treatment arm, 4-year OS was 95.0% (95% CI: 88.5%; 97.9%) in Iv-Arm and 96.7% (95% CI: 89.9%; 98.9%) in Sc-Arm.

Conclusion
This phase III study met its primary endpoint and demonstrated that Rsc induction followed by a short MRsc improves PFS of patients with low-tumor burden. MRsc did not however improved TTNLT. R in low-tumor burden FL allowed to avoid cytotoxic use in most patients 6 years after treatment initiation.

Keyword(s): Follicular lymphoma, Rituximab, Subcutaneous

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