Rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX) is an effective and safe salvage regimen in relapsed/refractory B-cell non-Hodgkin lymphoma.
ABSTRACT Salvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone.
We substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX.
Grade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT.
R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.
- [show abstract] [hide abstract]
ABSTRACT: A previous pilot study with rituximab, gemcitabine and oxaliplatin has shown promising activity in refractory/relapsed B-cell lymphoma. Therefore, we conducted a phase II study, in order to determine whether these results could be reproduced in a multi-institutional setting. This phase II study includes 49 patients with refractory (n=6) /relapsing (n=43) diffuse large B-cell lymphoma. Patients had a median age of 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplant in 17 (35%) patients. International Prognostic Index at enrolment was > 2 in 34 patients (71%). Primary objective was overall response rate after 4 cycles. Patients were planned to receive 8 cycles given in case if they reached partial remission after 4 cycles. After 4 cycles, responses were: complete remission 21 (44%), partial remission 8 (17%) resulting in an overall response rate of 61 %. Factors significantly affecting overall response rate were: early (< 1year) progression/relapse 18% vs 54% (p=0.001) and prior exposure to rituximab 23% vs 65% (p=0.004). Five-year Progression-Free and Overall Survival were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin was well tolerated with grade 3-4 infectious episodes in 22% of the cycles. These results are the first confirmation by a multi-institution study that Rituximab, gemcitabine and oxaliplatin provides a consistent response rate in refractory/relapsed patients. It can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195. The results were partly presented in an oral session at the American Society of Hematology annual meeting in Chicago, USA, in December 2010.Haematologica 06/2013; · 5.94 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Standard treatment for 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 (O), a monoclonal antibody against CD20, combined with ICE or DHAP second-line therapy in patients with relapsed or refractory DLBCL, grade 3b follicular lymphoma (FL), or transformed FL. Sixty-one patients were treated with either O-ICE (35) or O-DHAP (26). The overall response rate (ORR) was 61%, and the complete response (CR) rate was 37%. In patients with two or three adverse risk factors according to the second-line age-adjusted international prognostic index, ORR was 59% and CR 31%, and in patients with early-relapsing or primary refractory disease, 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 05/2013; · 9.06 Impact Factor
- Blood 07/2013; 122(4):469-70. · 9.06 Impact Factor