Ofatumumab vs Rituximab in Salvage Therapy for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
The final results of the international phase III ORCHARD study, reported in the Journal of Clinical Oncology by van Imhoff et al, showed no difference in progression-free survival with the addition of ofatumumab (Arzerra) vs rituximab (Rituxan) to cisplatin, cytarabine, and dexamethasone (O-DHAP vs R-DHAP) in relapsed or refractory diffuse large B-cell lymphoma. Initial results were reported in 2014.
Study Details
In the trial, 447 patients from 126 sites in 24 countries with CD20-positive diffuse large B-cell lymphoma aged > 18 years who had experienced first relapse or were refractory to first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)–like treatment were randomized between March 2010 and December 2013 to 3 cycles of R-DHAP or O-DHAP. Either ofatumumab at 1,000 mg or rituximab at 375 mg/m2 was given for 4 infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 and 3 of DHAP). Patients with response after two cycles received the third cycle, followed by high-dose therapy and autologous stem cell transplantation. The primary endpoint was progression-free survival, with absence of response after cycle 2 included as an event.
Patients had a median age of 57 years (17% aged ≥ 65 years), 63% had stage III or IV disease, and 71% did not have complete response or experience response for < 1 year on first-line R-CHOP.
No Difference in Outcomes
On the basis of the first trial analysis, follow-up was discontinued in November 2014, after occurrence of approximately 88% of progression-free survival events and 80% of deaths expected within 5 years. Response rates were 38% (complete response, 15%) in the O-DHAP group vs 42% (complete response, 22%) in the R-DHAP group. Autologous stem cell transplantation was completed on protocol by 33% vs 37% of patients. Two-year rates were 24% vs 26% for progression-free survival (hazard ratio [HR] = 1.12, P = .33), 16% vs 18% (HR = 1.10, P = .35) for event-free survival, and 41% vs 38% (HR = 0.90, P =.38) for overall survival.
Positron-emission tomography (PET)-negativity before autologous stem cell transplantation was highly predictive of superior outcome. For patients with negative vs positive scans after cycle 3, 2-year progression-free survival was 70% vs 32% (P = .001), and 2-year overall survival was 78% vs 43% (P = .0018).
The investigators concluded: “No difference in efficacy was found between O-DHAP and R-DHAP as salvage treatment of relapsed or refractory [diffuse large B-cell lymphoma].”
The study was sponsored by GlaxoSmithKline (GSK) and funded by GSK, Genmab A/S, and Novartis AG. Ofatumumab is an asset of Novartis AG as of March 2015.
Gustaaf W. van Imhoff, MD, PhD, of the University Medical Center Groningen, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
