Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma

Abstract

Key Points• Replacing rituximab with ofatumumab in second-line therapy for intermediate grade lymphoma does not increase toxicity; ORR/CR are encouraging.• An ongoing randomized phase III trial will compare rituximab with ofatumumab, combined with chemotherapy, in relapsed or refractory DLBCL.Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease. Nonetheless, outcomes are suboptimal for patients failing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We performed a multi-center phase II trial investigating the safety and efficacy of ofatumumab, a monoclonal antibody against CD20, combined with ICE or DHAP second-line therapy in patients with relapsed or refractory DLBCL, grade 3b follicular lymphoma, or transformed follicular lymphoma. Sixty-one patients were treated with either ofatumumab-ICE (35) or ofatumumab-DHAP (26). The overall response rate (ORR) was 61%, and the complete response (CR) rate was 37%. In patients with 2 or 3 adverse risk factors according to the second-line, age-adjusted, international prognostic index, the ORR was 59% and CR 31%, and in patients with early-relapsing or primary refractory disease, the ORR was 55% and CR 30%. Toxicity was largely hematologic, and stem cell mobilization was successful in 43 of 45 patients. Substitution of ofatumumab for rituximab in standard second-line regimens following failure of R-CHOP is a promising approach. This trial was registered at www.clinicaltrials.gov as NCT00823719. (Blood. 2013;122(4):499-506)

Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study

“…13,[15][16][17][18][19][20][21][22][23] In 6 studies that assessed different chemotherapy regimens for 251 patients who had aggressive lymphoma refractory to first-line therapy, the objective response rate ranged from 0% to 23%, and the median OS was ,10 months. 15,[17][18][19][20]22 In an additional 3 studies of 135 patients whose lymphoma was refractory to second-line therapy, the objective response rate ranged from 1% to 14%, and the median OS was 5 months. 18,21,24 Finally, in 2 studies of patients who relapsed after ASCT, median OS of 8 months (n 5 45) and 10 months (n 5 75) were reported.…”

Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study

“…Multiple new agents targeting various pathways in various combinations hold promise for improving survival in DLBCL. [30][31][32][33] Outcome after third-line DLBCL…”

Review of Antibody-Based Immunotherapy in the Treatment of Non-Hodgkin Lymphoma and Patterns of Use

“…41 Finally, 1 study evaluated ofatumumab in combination with ifosfamide carboplatin and etoposide or dexamethasone, cytarabine, and cisplatin as second-line therapy (after failure of R-CHOP [rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), prednisolone]) before autologous hematopoietic stem cell transplantation for intermediate grade lymphoma (DLBCL, grade III; FL; or transformed FL). 42 This study reported an RR of 61%, with 37% of those being CRs; furthermore, 45 of the 61 original patients were eligible for transplantation after ofatumumab-based chemoimmunotherapy. Stem cell mobilization was successful in 43 of the 45 eligible patients.…”