Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma

Abstract

Patients with relapsed or primary refractory diffuse large B-cell lymphoma (DL-BCL) who achieve complete response (CR) before autologous stem cell transplantation (ASCT) generally have better outcomes than those who achieve only partial response (PR). We investigated whether adding rituximab to the ifosfamide-carboplatin-etoposide (ICE) chemotherapy regimen (RICE) could increase the CR rate of patients with DLBCL under consideration for ASCT. Thirty-six eligible patients were treated with RICE, and 34 received all 3 planned cycles. The CR rate was 53%, significantly better than the 27% CR rate (P ‫؍‬ .01) achieved among 147 similar consecutive historical control patients with DLBCL treated with ICE; the PR rate was 25%. Febrile neutropenia was the most frequent grade 3 or 4 nonhematologic toxicity; it occurred in 7.5% of delivered cycles. No patient had RICErelated toxicity that precluded ASCT. The median number of CD34 ؉ cells per kilogram mobilized was 6.3 ؋ 10 6 . Progression-free survival rates of patients who underwent transplantation after RICE were marginally better than those of 95 consecutive historical control patients who underwent transplantation after ICE (54% vs 43% at 2 years; P ‫؍‬ .25). RICE appears to induce very high CR rates in patients with relapsed and refractory DLBCL; however, further studies are necessary to determine whether this treatment regimen will improve outcomes after ASCT.

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study

“…The most significant adverse prognostic factors for response in both the whole series and the R+ group were the presence of bulky disease, primary refractory disease, an aaIPI higher than 1 at the time of R-ESHAP, as well as the administration of fewer than three cycles of R-ESHAP. Moreover, the presence of primary refractory disease and high-risk aaIPI at the time of R-ESHAP were also independent adverse prognostic factors for survival, in accordance with reports from other authors, 9,13,14,[23][24][25][26] but in contrast to the data published by Kewalramani et al, 13 who observed that the addition of rituximab to the ICE regimen seemed to overcome the adverse effects of an unfavorable IPI score. The dismal outcome of patients with primary refractory disease or with an unfavorable aaIPI at the time of relapse underlines the need for the evaluation of alternative treatments.…”

“…Several studies have shown that when rituximab is added to salvage regimens such as DHAP/VIM/DHAP 12 or ICE 13 response rates and progression-free survival in patients with relapsed or refractory DLBCL are improved. However, the patients in these studies had not previously been exposed to rituximab.…”

“…In 225 evaluable patients, the addition of rituximab to second-line chemotherapy resulted in a significant improvement of overall response rate (75% versus 54%, p=0.01) and progression-free survival (52% versus 31% at 2 years, p<0.002). 12 Other small phase 2 trials (with a range of 35-55 patients) investigating rituximab in combination with ICE, 13 DHAP 14 or EPOCH 15 have also shown encouraging results. However, the patients in these studies had not been previously exposed to rituximab, while at present, almost all patients with aggressive B-cell nonHodgkin's lymphoma receive rituximab combined with first-line chemotherapy.…”

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

“…Rituximab has been shown to enhance cytotoxicity with cisplatin and overcome resistance to cisplatin and gemcitabine in-vitro (Demidem et al, 1997;Emmanouilides et al, 2002). Combination of rituximab with GEM-P may lead to improved CR rates similar to that seen with rituximab and ICE (Kewalramani et al, 2004). This may be important as some studies suggest that patients who undergo ASCT in CR do better than those in PR (Moskowitz et al, 1999).…”

A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin's lymphoma receiving chemotherapy

“…8 Additionally, in a recent study in which patients with relapsed or primary refractory diffuse large B-cell lymphoma received rituximab plus ICE, 28 (82%) of 34 patients receiving filgrastim 5-10 µg/kg/day mobilized sufficient CD34 + cells for transplantation. 11 The failure of some patients in this study to mobilize peripheral blood progenitor cells may be a function of disease severity -a high proportion of patients in each arm had been pretreated with salvage chemotherapy (66% for filgrastim vs 48% for both pegfilgrastim groups). It is noteworthy, however, that a numerically higher proportion of patients given filgrastim achieved optimal harvest despite more of them having received salvage treatment.…”