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The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients were stratified according to the modified International Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, age, and disease stage. The patients received 4 or 6 consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were evaluated by fluorodeoxyglucose-positron emission tomography scans performed at baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary objective of the trial was event-free survival (EFS) from randomization. The trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5-year EFS was not statistically significantly different between the 2 arms, with 89% ± 2.9% in the R-CHOP arm vs 92% ± 2.4% in the R-CHOP plus RT arm (hazard ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; P = .18). Overall survival was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R-CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT (P = not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in patients with nonbulky limited-stage DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT00841945.

The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients were stratified according to the modified International Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, age, and disease stage. The patients received 4 or 6 consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were evaluated by fluorodeoxyglucose-positron emission tomography scans performed at baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary objective of the trial was event-free survival (EFS) from randomization. The trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5-year EFS was not statistically significantly different between the 2 arms, with 89% ± 2.9% in the R-CHOP arm vs 92% ± 2.4% in the R-CHOP plus RT arm (hazard ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; P= .18). Overall survival was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R-CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT (P= not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in patients with nonbulky limited-stage DLBCL. This trial was registered at www.clinicaltrials.govas #NCT00841945.

No relevant conflicts of interest to declare.

Introduction:Continuous improvement in the management of Hodgkin Lymphoma (HL) has brought to favorable outcome for the majority of patients. However, patients with advanced stages still present unsatisfactory results with ABVD. The GOELAMS group conducted a prospective multicentric phase 2 trial for advanced stage HL with front-line therapy by VABEM and early salvage therapy followed by ASCT in case of absence of complete metabolic response to test a global PET adapted strategy with early salvage (LH 2007 trial, NCT00920153).

Le Gouill: Roche: Consultancy; Janssen: Consultancy. Dartigeas:Roche: Consultancy. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding. Gressin:MundiPharma: Other.

Background:

Consolidation using radioimmunotherapy (RIT) is a promising approach for elderly patients with diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem-cell transplantation. RIT using fractionated injections of 90Y-epratuzumab tetraxetan (Immunomedics, Inc.), a radiolabeled humanized anti-CD22 antibody, has been evaluated in relapsed patients with indolent or aggressive non-Hodgkin lymphoma (NHL), providing long-term disease control with manageable hematologic toxicities (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the LYSA group now assessed front-line treatment using fractionated RIT with 90Y-epratuzumab tetraxetan as consolidation therapy after R-CHOP in previously untreated elderly (age >60 years) patients presenting with stage I/II bulky or stage III/IV DLBCL.The trial included 6 courses of R-CHOP delivered q2wks followed by 2 infusions of 90Y-epratuzumab tetraxetan (2 × 15 mCi/m2 [555 MBq/m2], 7 days apart), 8 wks later. Patients were enrolled at time of diagnosis.From October 2008 to December 2010, 75 patients (41 males, 34 females) have been accrued prospectively at 19 French institutions. The median age was 69 (range, 60–79 years); 57 patients (76.0%) were Ann Arbor stage III/IV. Seventy-one of the 75 completed 6 courses of R-CHOP-14 and 61/75 (81.2%) were eligible for RIT. Thus, 14 patients were considered ineligible for RIT because of R-CHOP toxicity (N= 5), progressive disease (PD, N=3), patient refusal (N=3), or concomitant illness (N=3). RIT toxicity consisted of grade 3–4 hematologic toxicity in 51/61 patients (83.6%): grade 3–4 neutropenia in 46 (75.4%), grade 3–4 anemia in 15 (24.6%), and grade 3–4 thrombocytopenia in 47 (77.0%), with a nadir at 42, 48, and 43 days after RIT and a median duration of 18, 5, and 17 days, respectively. Following RIT, RBC and/or platelet transfusions were given to 31 patients (50.8 %). Serious febrile neutropenia was observed in 13 cases (17.3 %) after R-CHOP and in 3 patients (4.9%) following RIT. RIT's severe non-hematologic toxicity consisted of grade 4 gastrointestinal in 1 patient (1.6 %) and grade 4 infection in 3 (4.9%). No patient had mucositis after RIT. In the follow-up, 2 patients (2.6%) developed myelodysplastic syndrome 5 and 20 months after RIT.Using the 1999 International Workshop for Response Criteria for NHL (Cheson 1999), the overall response rate (ORR) after 6 × R-CHOP14 was 94.6% (71/75); 52 patients (69.3%) achieved CR/CRu and 19 (25.3%) had a partial response (PR). Among the 4 remaining patients, one had stable disease and 2 had PD; no assessment was obtained in the other. In an intention-to-treat analysis, CR/CRu rate after 6 × R-CHOP14 followed by RIT was 72.0% (N=54). Seven patients (9.3%) remained in PR and 8 (10.7%) progressed (2 patients previously in PR with PET-positive findings, 3 previously in CRu, including 1 PET-positive, and 3 in PD before RIT and then ineligible for RIT). No response assessment was obtained in the 6 others ineligible for RIT. At a median follow-up of 24 months (range, 1–46), 18 patients experienced lymphoma progression and/or a related death, yielding an estimated 2-year event-free-survival (EFS) of 73.3% (60.7-82.5%) and an estimated 2-year overall survival (OS) of 83.2% (71.4-90.4%). For the 61 patients who received 6 courses of R-CHOP followed by RIT consolidation, ORR was 91.8% (56/61); 50 patients (81.9%) achieved CR/CRu. Eight of 16 patients (50.0%) who had less than a CR/CRu with R-CHOP converted to CR/CRu after RIT. According to a PET analysis (Cheson 2007; N=55), 12 of the 24 patients (50.0%) who were not PET-negative after R-CHOP improved their metabolic response after RIT, resulting in a CR rate of 72.7%. Among these 61 patients, 12 experienced progression and/or a related death, yielding an estimated 2-year EFS of 78.7% (65.1–87.4%) and an estimated 2–year OS of 90.1% (77.7–95.8%).This phase II study clearly shows that fractionated RIT with 90Y-epratuzumab as a consolidation therapy after 6 × R-CHOP-14 is feasible and tolerable in elderly untreated DLBCL patients with advanced disease. RIT markedly improved response status observed after 6 × R-CHOP14. EFS data achieved with R-CHOP plus RIT compare favourably with those achieved with R-CHOP alone in the same patient population.Wegener: Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

Abstract 906This icon denotes a clinically relevant abstract

Radioimmunotherapy (RIT) is under study as a consolidation treatment after chemotherapy induction in follicular lymphoma patients. This approach also appears interesting in diffuse large B-cell lymphoma (DLBCL) patients >60 years, who are not candidates for bone marrow transplantation. 90Y-epratuzumab tetraxetan (Immunomedics, Inc.) is a radiolabeled humanized anti-CD22 antibody that has been used for a fractionated RIT, showing high rates of durable complete responses with manageable hematologic toxicity in previously-treated indolent and aggressive non-Hodgkin lymphoma (NHL) patients (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the GOELAMS group is ongoing, assessing fractionated RIT using 90Y-epratuzumab tetraxetan as a consolidation therapy after first-line chemotherapy in disseminated DLBCL patients >60 years. The protocol has been designed to include 75 patients; 64 patients have been already enrolled. We report the initial results, in particular safety data, on the first 29 available patients.From October 2008 to November 2009, 29 untreated DLCBL patients >60 years were studied in several French institutions with an initial course of six cycles of R-CHOP14 followed 8 weeks later by two weekly infusions of 90Y-epratuzumab tetraxetan (15 mCi/m2 [555 MBq/m2]) 7 days apart. Hematologic and non-hematologic toxicities were evaluated using NCI-CTC v.3.0. Treatment responses were classified according to the 1999 International Workshop for Response Criteria for NHL.Twenty-six patients underwent the entire course of R-CHOP and 23 received the 2 weekly RIT injections. Following R-CHOP, grade 3–4 neutropenia was observed in 20 patients (68.9%) and grade 3–4 thrombocytopenia in 4 (13.7%). During RIT infusions, 4 patients showed transient change of pulse or blood pressure, with 2 attributed to vasovagal reactions. RIT toxicity included grade 3–4 hematologic toxicity in 18 of 23 patients (78.3%); the most common grade > 3 toxicities were neutropenia (N=18, 78.3%) and thrombocytopenia (N=17, 73.9%). Serious febrile neutropenia was observed in 4 cases (13.8%) after R-CHOP and in 2 patients (8.7%) following RIT. Compared to R-CHOP, RIT non-hematologic toxicity was uncommon; moderate or severe gastrointestinal toxicity was observed in 10 patients (34.5%) after R-CHOP and in 2 (8.7%) following RIT; moderate or severe infection in 9 patients (31.0%) after R-CHOP and in 1 (4.3%) after RIT; and moderate or severe mucositis in 10 (34.4%) patients following R-CHOP, while no patient had mucositis after RIT. Following RIT, red cells and/or platelets transfusions were given to 12 patients (52,2%). Following R-CHOP, 10 of the 25 patients (40.0%) achieved a complete response (CR) or unconfirmed CR (CRu), 13 patients (52.0%) had a partial response (PR) and 2 patients (8.0%) had a stable disease. Six weeks after RIT, 13 patients (56.5%) achieved a CR or CRu, 9 patients (39.1%) had PRs, and 1 patient (4.3%) had progressive disease. Four of 13 patients (30.7%) who achieved less than a CR or CRu with R-CHOP improved their remission status 6 weeks after RIT.These preliminary results indicate the feasibility and safety of fractionated RIT with 90Y-epratuzumab as a consolidation therapy for elderly DLBCL patients. Additional data will be presented at the time of the communication.Off Label Use: monoclonal antibody epratuzumab labeled with yttrium 90 in phase II clinical trial. Wegener:Immunomedics, Inc.: Employment, shareholders. Goldenberg:Immunomedics, Inc.: Employment, shareholders.

Abstract 2875