Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study

Abstract

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with CD20 DLBCL age ≥ 18 years who had experienced their first relapse or who were refractory to first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like treatment were randomly assigned between three cycles of R-DHAP or O-DHAP. Either O 1,000 mg or R 375 mg/m was administered for a total of four infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 and 3 of DHAP). Patients who experienced a response after two cycles of treatment received the third cycle, followed by high-dose therapy and ASCT. Primary end point was progression-free survival (PFS), with failure to achieve a response after cycle 2 included as an event. Results Between March 2010 and December 2013, 447 patients were randomly assigned. Median age was 57 years (range, 18 to 83 years); 17% were age ≥ 65 years; 63% had stage III and IV disease; 71% did not achieve complete response (CR) or experience response for < 1 year on first-line R-CHOP. Response rate for O-DHAP was 38% (CR, 15%) versus 42% (CR, 22%) for R-DHAP. ASCT on protocol was completed by 74 patients (33%) in the O arm and 83 patients (37%) in the R arm. PFS, event-free survival, and overall survival were not significantly different between O-DHAP versus R-DHAP: PFS at 2 years was 24% versus 26% (hazard ratio [HR], 1.12; 95% CI, 0.89 to 1.42; P = .33); event-free survival at 2 years was 16% versus 18% (HR, 1.10; P = .35); and overall survival at 2 years was 41% versus 38% (HR, 0.90; P = .38). Positron emission tomography negativity before ASCT was highly predictive for superior outcome. Conclusion No difference in efficacy was found between O-DHAP and R-DHAP as salvage treatment of relapsed or refractory DLBCL.

Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

“…[10] Finally, the ORCHARRD study, in 447 patients with DLBCL, reported a 2-year EFS of around 15% and two-year OS of around 40% following ASCT. [11] The British National Lymphoma Investigation (BNLI) group was the first to compare HDT plus ASCT and conventional chemotherapy in HL. [12] Their study demonstrated a three-year event-free survival (EFS) of 53% in chemo-sensitive patients receiving BEAM followed by ASCT, compared to 10% in patients given lower doses of BEAM (mini-BEAM) without ASCT (p ¼ 0.025); there was no significant difference in OS between groups.…”

Ofatumumab Exhibits Enhanced In Vitro and In Vivo Activity Compared to Rituximab in Preclinical Models of Mantle Cell Lymphoma

“…In the setting of aggressive B-NHL, ofatumumab in combination with dexamethasone, cytarabine, and cisplatin or ifosfamide, carboplatin and etoposide (DHAP or ICE) resulted in an ORR of 61% in patients with relapsed/primary refractory disease following at least one prior rituximab containing regimen (27). However, in a recently reported large international trial investigating ofatumumab head to head with rituximab in combination with DHAP in relapsed/refractory DLBCL, the ORR to O-DHAP was significantly lower at 38% and was similar to that of R-DHAP (42%) with no difference in progression free or overall survival between groups (28). Of note, in 19 previously untreated older (>65 years) patients with MCL, the combination of ofatumumab, bendamustine, and dexamethasone resulted in an ORR of 94% with 89% of those achieving a CR (29).…”

Spanish Lymphoma Group (GELTAMO) guidelines for the diagnosis, staging, treatment, and follow-up of diffuse large B-cell lymphoma

“…Therefore, the best option for these patients is to enroll them in clinical trials of regimens that include new drugs. In this context, the substitution of rituximab with ofatumumab showed no benefit in a randomized study [48]. …”