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1370 Final Analysis of a Prospective Multicenter Phase II Trial of the Lymphoma Study Association (LYSA) Using Prednisone, Vinblastine, Doxorubicin and Bendamustine (PVAB) Regimen in First Line Therapy for Patients over 60 Years with Advanced-Stage Classical Hodgkin Lymphoma

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Trials, Hodgkin Lymphoma, Lymphomas, Clinical Research, Elderly, Diseases, Lymphoid Malignancies, Study Population
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Herve Ghesquieres, MD1*, Rene-Olivier Casasnovas, MD2*, Emmanuelle Nicolas-Virelizier, MD3*, Salim Kanoun4*, Gandhi Laurent Damaj, MD, PhD5*, Vincent Delwail, MD6*, Arnaud Jaccard7*, Kamel Laribi, MD8*, Franck Morschhauser, MD, PhD9*, Christophe Bonnet, MD10*, Agathe Waultier, MD11*, Frederique Orsini-Piocelle, MD12*, Marc Andre, MD13*, Marguerite Fournier14*, Fabienne Morand15*, Alina Berriolo-Riedinger, MD16*, Diane Damotte, MD, PhD17*, Alexandra Traverse-Glehen, MD, PhD18*, Philippe Quittet, MD19* and Pauline Brice, MD20*

1Department of Hematology, Hopital Lyon Sud, Pierre Benite, France
2Department of Hematology, CHU Dijon, Dijon, France
3Department of Hematology, Centre Leon Berard, Lyon, France
4Nuclear Medicine, Institut universitaire du cancer Toulouse- Oncopole, Toulouse, France
5Department of Hematology, CHU Caen, Caen, France
6Department of Hematology, CHU Poitiers, Poitiers, France
7Department of Hematology, CHU Limoges, Limoges, France
8Department of Hematology, CH Le Mans, Le Mans, France
9Hematology Department, Lille University Hospital, Lille, France
10Department of Hematology, Liege University Hospital, Liege, Belgium
11Department of Hematology, CHU Nimes, Nimes, France
12Department of Hematology, Centre Hospitalier Annecy Genevois, Pringy, France
13Department of Hematology, CHU de Mont Godinne, Yvoir, Belgium
14Department of Statistics, LYSARC, Pierre Benite, France
15Department of Clinical Research, LYSARC, Pierre Benite, France
16Département de Médecine nucléaire, Centre Georges François Leclerc, Dijon, France
17Département de Pathologie, APHP, Hôpital Cochin, Paris, France
18Department of Pathology, Hopital Lyon Sud, Pierre-Benite, France
19Department of Hematology, CHU Montpellier, Montpellier, France
20Department of Hematology, Hôpital Saint-Louis, Paris, France

Introduction: Older classical Hodgkin lymphoma (cHL) patients are characterized by a significant reduced survival as compared to younger patients. In relapsed and refractory HL, prospective and retrospective studies showed that bendamustine monotherapy provided interesting efficacy with 30% of complete response with an acceptable toxicity profile. We developed the PVAB (Prednisone, Vinblastine, Doxorubicin, Bendamustine) regimen in first line therapy to improve prognosis of older HL with advanced stage.

Methods: In this prospective phase II, we recruited newly diagnosed classical HL patients age of 61 years or older with an advanced stage (Ann Arbor stage III, IV, IIB with risk factors). Inclusion criteria were: ECOG performance status 0-2; adequate cardio-pulmonary function with LVEF ≥ 50%; adequate renal function with creatinine clearance ≥ 40 mL/min; HIV negative; For patients aged 70 years old and more, a Mini Nutritional Assessment (MNA) ≥ 17. Treatment consisted of 6 cycles of prednisone (40mg/m2 D1-5), vinblastine (6mg/m2, D1), doxorubicin (40mg/m2, D1) and bendamustine (120mg/m2, D1) every 21 days. The primary endpoint was the complete metabolic response (CMR) rate according to local review after 6 cycles of study treatment or at premature treatment discontinuation according to Lugano Classification. We presented the final analysis of the study with a median follow-up of 42 months (range, 0.5-63.8), with prognostic analyses for progression free survival (PFS) measured from the date of inclusion to the date of progression, relapse or death from any cause. Prognostic factors included baseline clinical and biological characteristics, geriatric assessments and 18F-FDG PET/CT metabolic parameters especially baseline total metabolic tumor volume (TMTV). Optimal thresholds for some parameters were calculated using X-Tile approach.

Results: Between July 2015 and July 2018, 89 patients were included in 34 LYSA centers. The median age was 68 years (range, 61-88) with 35 patients ≥70 years old (39%). The main histological subtype was nodular sclerosis cHL (n=56, 63%) with 26 EBV associated cases (LMP1 staining). Ann Arbor stages were as follows: II (n=3, 3%), III (n=30, 34%), IV (n=56, 63%). B symptoms were present in 57% of patients; 70 patients (80%) had IPS≥3. The median of CIRS-G score was 3 (range, 0-12). Seventy-eight patients (88%) completed the 6 cycles of PVAB. Update results for toxicity showed that 28 patients (32%) presented at least one serious adverse event (SAE) in particular infections (n=13, 15%), blood (n=11, 12%) and cardiac disorders (n=4, 4.5%). The CMR rate according to local review corresponding to the primary endpoint of the study was 77.5% (95%CI, 67-86) with 69 patients in CMR. After central review of 79 available PET/CT images, the CMR rate was 78.5%. Thirty-one patients relapsed or progressed (35%). The 4-year PFS rate was 50% (95%CI, 39-61). For the 69 patients achieving CMR, the 4-year disease free survival (DFS) rate was 62.8% (95%CI, 49-74). Twenty-four patients (27%) died: 11 cHL (46%), 4 treatment toxicity (17%), 6 second cancers (25%), 3 other causes after treatment (infection, cardiac insufficiency, pulmonary embolism, 12%). The 4-year overall survival rate was 69% (95%CI, 57-79). In univariate analysis, altered ECOG PS, Ann Arbor stage IV, bulky disease (>7cm), B-symptoms, extra-nodal involvement (>1), bone or medullar involvement, liver involvement, albumin (≤30g/l), hemoglobin level (<10.5g/dl), lymphocyte count (<0.8 G/L), leucocyte count (≥12G/L), CD4+ lymphocyte count (<0.41G/L), B2 microglobuline level (3 mg/l), CRP level (>88mg/l), TMTV (>450ml) and number of medications non-related to HL (>5) were associated with PFS. In multivariate analysis, liver involvement (HR: 3.79; 95%CI,1.71-8.43; P=0.001), lymphopenia (HR: 3.04; 95%CI,1.54-6.01; P=0.001), CRP (HR: 3.37; 95%CI, 1.69-6.69; P=0.0005) and co-medications (HR: 2.85; 95%CI,1.44-5.66; P=0.003) were independently associated with PFS.

Conclusions: PVAB regimen provided high CMR (77.5%) with acceptable toxicity for advanced stage cHL patient over 60 years. The 4-year PFS and OS rates were 50% and 69% respectively, these survival endpoints were influenced by not related-lymphoma events. Prognostic analyses showed that specific involved site (liver), biological parameters (lymphocyte count and CRP) and patient’s comorbidity (co-medications) influenced independently PFS.

Disclosures: Ghesquieres: Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Roche: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Mundipharma Research Limited: Consultancy, Honoraria; Takeda: Other: Travel, accommodation, expenses. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Jaccard: Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Abbvie: Honoraria. Laribi: Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding. Morschhauser: Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Chugai: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech, Inc.: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brice: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; MSD: Honoraria.

OffLabel Disclosure: Bendamustine is off-label drug use in Hodgkin lymphoma

*signifies non-member of ASH