Results of a prospective phase II trial with ofatumumab as part of reduced intensity conditioning regimen in high‐risk non‐ H odgkin B lymphoma patients: A GELTAMO trial

Abstract

Allogeneic transplantation (AlloSCT) is the only curative option for high-risk non-Hodgkin lymphoma (NHL) patients. Reduced intensity conditioning (RIC) is commonly used in these patients, but best regimen is still not fully established. Treatment with anti-CD20 monoclonal antibodies improved outcome of NHL, but they have not been widely used in AlloSCT. Rituximab has been added to the conditioning regimen in the setting of AlloSCT, but there are no data about new anti-CD20 monoclonal antibodies as Ofatumumab and its effect on disease control, graft versus host disease (GVHD) incidence and longterm response. We designed a phase II clinical trial (NCT01613300) with Ofatumumab as a part of a RIC regimen in high-risk non-Hodgkin lymphoma patients. Primary end point was grade 3-4 acute GVHD rate, and secondary end point was complete response (CR) rate. Patients and Methods: Inclusion criteria were: less than a partial response (PR) after 2 lines of chemotherapy, relapse after an autologous SCT (ASCT), evidence of disease 3 months after ASCT, failure in mobilization for ASCT, or PR after a previous relapse after 2 lines of treatment with risk factors such like CR <12 months after ASCT. Conditioning regimen: Ofatumumab 300 mg day -20, 2000 mg days -13 and -6 and 1000 mg days +1 and +8, plus fludarabine 150 mg/msq days -7 to -3 and melphalan 70 mg/ msq days -2 and -1. In relapses <12 months after ASCT: melphalan 70 mg/ msq + Thiotepa 5 mg/msq day -8. GVHD prophylaxis: sirolimus + tacrolimus. Results: We included 33 patients from 6 centers. Two patients abandoned the protocol, so 31 patients were evaluable. Median age was 51 years (30-65). Donor was HLA identical in 23 (74%). Diagnosis were diffuse large B-cell lymphoma (DLBCL) in 21 patients (64%), mantle cell lymphoma (MCL) in 6 (28%), grade 3 follicular lymphoma (FL) in 3 (9%) and transformed NHL in 3 (9%). Eighteen (55%) had received a prior ASCT, 70% had stage IV disease, 73% had received 3 or more lines of therapy and 42% were not in CR before AlloSCT. Infusions were well tolerate, with 5 cases of grade I-II cutaneous rash, 1 case of grade I headache and 1 grade II allergic reaction, all of them resolved. At day +100, 24 patients (77%) were in CR, 1 (2%) was in PR and 4 (6%) experienced disease progression; 2 patiens were not evaluable because of early mortality. Acute GVHD was diagnosed in 25 (76%) with 5 cases (14%) of grade 3-4 aGVHD. In 73% of patients, GVHD achieved CR after treatment. Chronic GVHD appeared in 13/29 (48%) patients alive at day +100, at it was mild or moderate in 97%. At last follow-up, 5 patients relapsed after a median of 3 months (1-6) and overall mortality rate was 42% (n = 13); cause of death was progression disease in 3 and transplant related mortality in 10. Estimated progression-free survival (PFS) at 24 months was 50%, with a median estimated PFS of 23 months (6-39). Conclusion: Ofatumumab is feasible as a part of RIC regimen in highrisk B NHL patients. Although aGVHD rate was 76%, there were no grade 4 cases and 73% of patients responded to treatment achieving CR. Based on these data, future prospective studies are warranted.