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

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1370-1370
• Main Authors: Ghesquieres, Herve, Casasnovas, Rene-Olivier, Nicolas-Virelizier, Emmanuelle, Kanoun, Salim, Damaj, Gandhi Laurent, Delwail, Vincent, Jaccard, Arnaud, Laribi, Kamel, Morschhauser, Franck, Bonnet, Christophe, Waultier, Agathe, Orsini-Piocelle, Frederique, Andre, Marc, Fournier, Marguerite, Morand, Fabienne, Berriolo-Riedinger, Alina, Damotte, Diane, Traverse-Glehen, Alexandra, Quittet, Philippe, Brice, Pauline
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-152346

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/m 2 D1-5), vinblastine (6mg/m 2, D1), doxorubicin (40mg/m 2, D1) and bendamustine (120mg/m 2, 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 serio