The phase 2 LYSA study of prednisone, vinblastine, doxorubicin, and bendamustine for untreated Hodgkin lymphoma in older patients

• Published in: Blood 2024-03, Vol.143 (11), p.983-995
• Main Authors: Ghesquières, Hervé, Krzisch, Daphné, Nicolas-Virelizier, Emmanuelle, Kanoun, Salim, Gac, Anne Claire, Guidez, Stéphanie, Touati, Mohamed, Laribi, Kamel, Morschhauser, Franck, Bonnet, Christophe, Waultier-Rascalou, Agathe, Orsini-Piocelle, Frédérique, André, Marc, Fournier, Marguerite, Morand, Fabienne, Berriolo-Riedinger, Alina, Burroni, Barbara, Damotte, Diane, Traverse-Glehen, Alexandra, Quittet, Philippe, Casasnovas, Olivier
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bendamustine Hydrochloride - adverse effects; Cyclophosphamide; Doxorubicin - adverse effects; Hodgkin Disease - pathology; Humans; Middle Aged; Prednisone - adverse effects; Prospective Studies; Vinblastine - adverse effects; Vincristine
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023021564

•The PVAB regimen yielded a CMR rate of 77.5% as a firstline therapy for older patients with HL, with acceptable toxicity.•The 4-year cumulative risk of events was 35% for progression and relapse, 9% for death from lymphoma, and 6% for nonlymphoma events. [Display omitted] Older patients with classical Hodgkin lymphoma (cHL) require more effective and less toxic therapies than younger patients. In this multicenter, prospective, phase 2 study, we investigated a new firstline therapy regimen comprising 6 cycles of prednisone (40 mg/m2, days 1-5), vinblastine (6 mg/m2, day 1), doxorubicin (40 mg/m2, day 1), and bendamustine (120 mg/m2, day 1) (PVAB regimen) every 21 days for patients with newly diagnosed cHL aged ≥61 years with an advanced Ann Arbor stage. A Mini Nutritional Assessment score ≥17 was the cutoff value for patients aged ≥70 years. The primary end point was the complete metabolic response (CMR) rate after 6 cycles. The median age of the 89 included patients was 68 years (range, 61-88 years), with 35 patients (39%) aged ≥70 years. Seventy-eight patients (88%) completed the 6 cycles. The toxicity rate was acceptable, with a 20% rate of related serious adverse events. CMR was achieved by 69 patients (77.5%; 95% confidence interval [CI], 67-86). After a median follow-up of 42 months, 31 patients progressed or relapsed (35%), and 24 died (27%) from HL (n = 11), toxicity during treatment (n = 4), secondary cancers (n = 6), or other causes (n = 3). The 4-year progression-free survival (PFS) and overall survival rates were 50% and 69%, respectively. Multivariate analysis showed that liver involvement (P = .001), lymphopenia (P = .001), CRP (P = .0005), and comedications (P = .003) were independently associated with PFS. The PVAB regimen yielded a high CMR rate with acceptable toxicity. Over long-term follow-up, survival end points were influenced by unrelated lymphoma events. This trial was registered at www.clinicaltrials.gov as #NCT02414568 and at EudraCT as 2014-001002-17. Older patients with classical Hodgkin lymphoma (cHL) tolerate intensive bleomycin-containing chemotherapy regimens poorly. Ghesquières and colleagues report on results of a phase 2 study of a new regimen comprised of doxorubicin (Adriamycin), vinblastine, bendamustine, and prednisone in 89 patients aged 61 and over with advanced cHL. Complete metabolic response as determined by positron emission tomography scan was achieved in 78% of patients; progression-free survival and overall s