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

Abstract

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.

Figure 1

Treatment protocol. Routine cycle length was 21 days. *Stem cell mobilization could be performed in cycle 2 and/or cycle 3. FL, follicular lymphoma; Gr3B, grade 3B; O, ofatumumab; PD, progressive disease.

Figure 2

CONSORT diagram of distribution of patients according to treatment assignation. O, ofatumumab.

Figure 3

Progression free survival. (A) PFS for O-DHAP and O-ICE. Median PFS for O-DHAP was 301 days (95% confidence interval [CI] 152, not estimable); median PFS for O-ICE was 288 days (95% CI 177, not estimable). (B) PFS according to saaIPI, 0 to 1 risk factors vs 2 to 3 risk factors. Median PFS for 0 to 1 risk factors was not reached (95% CI: 288, not estimable), median PFS for 2 to 3 risk factors was 177 days (95% CI 117, 264). (C) PFS according to response to first-line therapy, CR >12 months vs CR ≤ 12 months or failure to achieve remission. Median PFS for CR >12 months was not reached (95% CI 375, not estimable); median PFS for CR ≤ 12 months or failure to achieve remission was 261 days (95% CI 152, 296). O, ofatumumab.