Search

We aimed to compare AIDS risk–adapted intensive chemotherapy in AIDS-related lymphoma (ARL) patients before and after the advent of highly active antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years were randomly assigned to chemotherapy after stratification according to an HIV score based on performance status, prior AIDS, and CD4+cell counts below 0.10 × 109/L (100/mm3). A total of 218 good-risk patients (HIV score 0) received ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177 intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90 poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The 5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47% for CHOP (P= .85); in the intermediate-risk group, 28% for CHOP versus 24% for Ld-CHOP (P= .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS (P= .14). The time-dependent Cox model demonstrated that the only significant factors for OS were HAART (relative risk [RR] 1.6, P< .001), HIV score (RR 1.7, P< .001), and the International Prognostic Index (IPI) score (RR 1.5, P< .001) but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV score, IPI score, and HAART affect survival but not the intensity of the CHOP-based chemotherapy.

We aimed to compare AIDS risk–adapted intensive chemotherapy in AIDS-related lymphoma (ARL) patients before and after the advent of highly active antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years were randomly assigned to chemotherapy after stratification according to an HIV score based on performance status, prior AIDS, and CD4+ cell counts below 0.10 × 109/L (100/mm3). A total of 218 good-risk patients (HIV score 0) received ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177 intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90 poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The 5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47% for CHOP (P = .85); in the intermediate-risk group, 28% for CHOP versus 24% for Ld-CHOP (P = .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS (P = .14). The time-dependent Cox model demonstrated that the only significant factors for OS were HAART (relative risk [RR] 1.6, P < .001), HIV score (RR 1.7, P < .001), and the International Prognostic Index (IPI) score (RR 1.5, P < .001) but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV score, IPI score, and HAART affect survival but not the intensity of the CHOP-based chemotherapy.

In diffuse large B-cell lymphoma (DLBCL), the combination of rituximab and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone; R-CHOP) has been shown to be more effective than CHOP for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in patients with DLBCL. To establish whether or not rituximab reduces bcl-2—associated treatment failure, we studied bcl-2 protein expression and clinical outcome in patients included in the Groupe d’Etude des Lymphomes de l’Adulte LNH-98-5 trial. Patients between 60 and 80 years of age were randomized to receive 8 cycles of either CHOP or R-CHOP every 3 weeks. Of the 399 patients included, 292 with histologically proven DLBCL had material available for bcl-2 study. Tumors were considered positive when at least 50% of tumor cells expressed bcl-2 protein.

In diffuse large B-cell lymphoma (DLBCL), the combination of rituximab and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone; R-CHOP) has been shown to be more effective than CHOP for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in patients with DLBCL. To establish whether or not rituximab reduces bcl-2—associated treatment failure, we studied bcl-2 protein expression and clinical outcome in patients included in the Groupe d'Etude des Lymphomes de l'Adulte LNH-98-5 trial. Patients between 60 and 80 years of age were randomized to receive 8 cycles of either CHOP or R-CHOP every 3 weeks. Of the 399 patients included, 292 with histologically proven DLBCL had material available for bcl-2 study. Tumors were considered positive when at least 50% of tumor cells expressed bcl-2 protein. There were 193 (66%) bcl-2+ patients and 99 (34%) bcl-2– patients. The response rates for R-CHOP and CHOP were, respectively, 78% and 60% (P = .01) in bcl-2+ patients and 76% and 73% (P = .7) in bcl-2– patients. At a median of 2 years of follow-up, R-CHOP was significantly associated with a better overall survival than CHOP in bcl-2+ patients (67% ± 9% versus 48% ± 11%, P = .004). In bcl-2– patients there was no statistically significant difference (72% ± 12% versus 67% ± 14%, P = .6). In addition, R-CHOP was associated with significantly better event-free survival than CHOP in bcl-2+ patients (58% ± 10% versus 32% ± 10%, P < .001) but not in bcl-2– patients (60% ± 13% versus 40% ± 15%, P = .13). Multivariate analysis confirmed the significant benefit for survival and event-free survival of R-CHOP in bcl-2+ patients. These results suggest that rituximab is able to prevent chemotherapy failure in patients with bcl-2 protein overexpression.

ABSTRACTThe pharmacokinetics and safety of an intravenous hydroxypropyl-β-cyclodextrin solution of itraconazole administered for 7 days followed by itraconazole oral solution administered at 200 mg once or twice daily for 14 days were assessed in 17 patients with hematologic malignancies. Steady-state plasma itraconazole concentrations were reached by 48 h after the start of intravenous treatment. The mean trough plasma itraconazole concentration at the end of the intravenous treatment was 0.54 ± 0.20 μg/ml. This concentration was not maintained during once-daily oral treatment but increased further in the twice-daily treatment group, with a trough itraconazole concentration of 1.12 ± 0.73 μg/ml at the end of oral treatment. As expected in the patient population studied, all patients experienced some adverse events (mainly gastrointestinal). Biochemical and hematologic abnormalities were frequent, but no consistent changes occurred. In conclusion, 7 days of intravenous treatment followed by 14 days of twice-daily oral treatment with itraconazole solution enables plasma itraconazole concentrations of at least 0.5 μg/ml to be reached rapidly and to be maintained. The regimen is well tolerated and has a good safety profile.

On Behalf of the European Mantle Cell Lymphoma Network

Walewski: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Servier: Consultancy, Honoraria. Thieblemont: Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Salles: Epizyme: Consultancy, Honoraria; Velosbio: Consultancy; Loxo: Consultancy; Genmab: Consultancy; Incyte: Consultancy; Ipsen: Consultancy; Kite/Gilead: Consultancy; Janssen: Consultancy; Genentech/Roche: Consultancy; Miltneiy: Consultancy; Morphosys: Consultancy, Honoraria; Rapt: Consultancy; Novartis: Consultancy; Allogene: Consultancy; Debiopharm: Consultancy; Takeda: Consultancy; Regeneron: Consultancy, Honoraria; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria. Feugier: ROCHE: Membership on an entity's Board of Directors or advisory committees, Other: Meeting travel funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel funding. Hübel: Celgene: Consultancy; Gilead: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; EUSA: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau. Klapper: Takeda: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; Amgen: Research Funding; Roche: Consultancy, Research Funding. Unterhalt: Roche: Research Funding. Dreyling: Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Gilead Kite: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Research Funding; BeiGene: Consultancy, Speakers Bureau; Genmab: Consultancy; MorphoSys: Consultancy.

Although the recognition of hybrid acute leukemia (HAL) is still controversial, several reports have described cytogenetic findings in these leukemias over the last 3 years. A distinct chromosomal profile appears to be associated with different immunologic subsets of HAL. The classical t(15;17). and inv(16) as well as abnormalities of the long arm of chromosome 5 and/or 7 are preferentially associated with acute myeloid leukemia (AML) with T-cell features: the t(8;21)(q22;q22), the Ph chromosome, and 11q23 rearrangements are more frequently found in AML with B-cell features; the Ph chromosome, t11q23 and 11q32 breaks without rearrangements of the immunoglobulin heavy chain gene may be associated with acute lymphoblastic leukemia (ALL) with myeloid markers.In addition, some chromosome aberrations may be encountered more frequently in acute leukemia with major phenotype deviations than in unselected cases of acute leukemia: namely the Ph chromosome, 11q23 rearrangements, arid + 13. These chromosome changes appear to be associated with a low complete remission (CK) rate. An association has been documented in, some patients with ALL between the presence of the t(9;22) and a minor myeloid component consisting of 5-15% blast cells with myelomonocytic features, raising the possibillity that a diagnosis of bilineal acute leukemia would be more appropriate in such cases. These patients appear to have a severe outcome with significantly lower CF. rate than similar cases of Ph-positive ALL without a minor myeloid component. From these data the conclusion can be drawn that, although the chromosomal profile of HAL is far from being complete, a multiparameter analysis, combining morphology. immunology and cytogenetics may represent a valuable tool in clinical practice for a correct classification of these leukemias.

Cytogenetic patterns in correlation with cytologic, biomolecular and clinical findings were studied in 45 adult patients with AML expressing at least one of the following lymphoid associated markers (LM): CD2, CD7, CD10, CD19, CD22, TdT. Four cytogenetic groups were recognized: group I, including 8 patients with 11q23 rearrangements; group II including S patients with the Ph chromosome; group III, with 19 patients and aberrations of the "myeloid type" including 4 cases with aberrations of chromosome 13, 3 cases with lq and 7q anomalies, 2 cases with trisomy 1 lq; group IV, including 13 patients with normal karyotype.Patients showing extensive lineage infidelity were encountered more frequently in cytogenetic groups I and II than in groups III and IV. Two of 4 cases with aberrations of chromosome 13 showed two or more lymphoid features either at immunophenotyping or at biomolecular analysis of the configuration of lg and TCR genes. Patients with 1 Iq23 rearrangements and with the Ph chromosome were generally young, presented with high WBC count and had low complete remission rate. Survival in Ph chromosome positive patients was uniformly short. We conclude that, although there is no cytogenetic anomaly specific for AML with LM, chromosome findings may be clinically relevant in AML with LM. A morphologic, immunologic and cytogenetic classification of AML with LM may constitute a working basis for future studies aimed at a better definiton of clinicopathological features and optimal treatment strategy for these leukemias.

Cytogenetic, biomolecular, and clinicopathologic features were retrospectively studied in 34 adult patients with acute myelogenous leukemia expressing one or more of the following lymphoid-associated markers (LMs): CD7, CD2, CD10, CD19, CD22, TdT. Six patients showed 11q23 rearrangements (group I); three patients had the classic Ph chromosome (group II); 15 patients had aberrations of the myeloid type (group III), including four patients with structural aberrations of 13q or trisomy 13, three patients with 7q and 1q anomalies, and two patients with trisomy 11q. Ten patients had a normal karyotype (group IV). Anomalies exclusively associated with lymphoid malignancies were not seen. Ig H and/or T-cell receptor genes were found to be rearranged in 50% and 66% of patients in cytogenetic groups I and II, respectively, versus 8% in group III and 12% in group IV. Likewise, more than one LM was more frequently detected in groups I and II. In group III, two of four patients with aberrations of chromosome 13 expressed two or more lymphoid features. Clinically, patients belonging to cytogenetic groups I and II were generally young, presented with a high white blood cell (WBC) count, and had a low complete remission rate. Survival in Ph chromosome-positive cases was uniformly short. We conclude that although there is no cytogenetic anomaly specifically associated with acute myelogenous leukemia expressing LM, a Morphologic, Immunologic, and Cytogenetic classification may constitute a working basis for further studies aimed at a better definition of clinicopathologic features and optimal treatment strategies for these leukemias.© 1992 by The American Society of Hematology. 0006-497119217903-0010$3.0010

Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlym-phocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evalu-able patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed-7/7q– and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13or14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of – 7/7q– and –5/5q– in ANLL-M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells.

The purpose of this study was to, assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty two patients with intermediate- or high-grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84 regimen every 2 weeks, with an open randomization to treatment with anthracyclines. Patients were randomized to receive subcutaneous lenograstim 5 μg/kg/day (n = 82) or placebo (n = 80) from day 6 to day 13 of each cycle.The incidence of severe neutropenia (absolute neutrophil count (ANC) < 0.5 × 109/L) was reduced in the lenograstim group compared with placebo (52% vs 75%). A significant reduction (p < 0.001) in the median duration of ANC < 0.5 × 109/L was also observed in patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2-4 days in placebo recipients). Fever occurred in 66 patients in each treatment group. Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 × 109/L compared with 18.5% of lenograstim-treated patients (p < 0.05). Infections of ≥grade 2 severity were significantly less frequent (p = 0.001) among lenograstim recipients compared with placebo (25 vs 49). The most common adverse events among lenograstim recipients were headache, mild bone pain and injection site reactions. Although lenograstim significantly increased (p = 0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed.The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim. Furthermore, lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals, even in patients with bone marrow involvement, and may permit further dose escalation of the chemotherapeutic regimen used.

Thieblemont: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Bayer healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gomez da Silva:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; ROche: Consultancy, Membership on an entity's Board of Directors or advisory committees; takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Meyer Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. Morschhauser:Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Janssen: Honoraria; Servier: Consultancy, Honoraria. Haioun:Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cabecadas:celgene: Consultancy, Honoraria. Salles:Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Mundipharma: Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Coiffier:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background.R-CHOP is the standard first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). However 30% of patients will relapse and 70% of relapsed patients will die within 2 years of diagnosis. The REMARC study (clinicalTrials.gov NCT01122472) is an international, multicenter, double-blind, randomized, placebo controlled, phase III trial that assessed the benefit of lenalidomide (LEN) maintenance after response to R-CHOP in patients aged 60 to 80 years with untreated DLBCL, FL3b or transformed lymphoma. Patients achieving CR or PR at the end of 6 or 8 cycles of R-CHOP21 or R-CHOP14 were stratified by CR/PR status and country and randomized 1:1 to receive 2 years of LEN maintenance (25 mg/day for 21 of every 28 days) or placebo (PBO). The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints were safety, PR to CR conversion rate, and overall survival (OS). Diagnosis was retrospectively centrally reviewed. In patients with adequate samples, GCB/nonGCB profile was assessed by the Hans algorithm and GCB/ABC/unclassified profile was assessed using NanoString gene expression profiling technology.

There are some evidences that blood transfusions, either red blood cell (RBC) or platelet, could impact survival of patients affected with various medical conditions. Mechanisms are largely unknown but immune dysfunction, storage duration, cytokines or iron releases could be involved. These concerns led to the publication of revised guidelines with a more restrictive approach for RBC and platelet transfusions in various conditions, mostly surgery and emergency. However, less was known for cancer patients receiving therapy with a curative attempt.

Anemia is a common feature at diagnosis of patients with lymphoid malignancies and has been previously described as an important prognostic factor (Moullet et al. Ann Oncol 1998). Recent guidelines recommend evaluating iron parameters as part of the initial assessment of cancer associated anemia in order to propose iron therapy for patients with functional or absolute iron deficiency. However, incidence of iron parameters abnormalities and impact on prognosis is largely unknown.The phase III randomized LNH 03-6B protocol included elderly patients from 60 to 80-year with untreated diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index (aaIPI) of 1 or more. Patients were randomized between 8 cycles of R-CHOP given every 2 or 3 weeks (Delarue et al. Lancet Oncol 2013) and between a prophylactic treatment with Darbepoetin alfa in order to maintain hemoglobin level between 13 and 14 g/dL versus an usual management of chemotherapy-induced anemia including ESAs and transfusions. Iron parameters including serum iron, transferrin and ferritin levels and transferrin saturation (TSAT) were measured at screening and at the end of study treatment. Iron deficiency was defined by TSAT below 20% and was considered either as true or functional if ferritin level was below or above normal or value, respectively.At diagnosis, median serum iron level was 9 µmol/L (n=358 patients, range: 0.14-62.6), median transferrin level was 2.1 g/L (n=262 patients, range: 0.3-29), median ferritin level was 325 ng/mL (n=321 patients, range: 6-6071) and median TSAT was 17% (n=258 patients, range: 2-57). Among patients with available TSAT data, 163/258 (63%) presented a coefficient lower than 20%. When comparing with the whole study population, patients with TSAT = 20% had similar baseline characteristics including aaIPI. In univariate analysis, there is no difference of PFS (HR: 1.078, 95%CI: 0.734-1.584, p=0.7006) and OS (HR: 0.963, 95%CI: 0.622-1.491, p=0.8664) according to TSAT. By contrast, in univariate and multivariate analysis, patients with ferritin level lower than normal and patients with ferritin level higher than normal presented, compared with patients with normal ferritin level, worse PFS (respectively, HR: 4,973, 95%CI: 1.673-14.780, p=0.039; HR: 1,654, 95%CI: 1.094-2.499, p =0,017) and OS (respectively HR: 6.204, 95%CI: 1.713-22.475, p=0.0055; HR: 1.8, 95%CI: 1.108-2.923, p =0.0175).Elderly patients with untreated aggressive lymphoma and iron deficiency as measured by TSAT showed similar characteristics compared to the whole population. TSAT level did not impact prognosis in contrast to ferritin level, whose variations could be independent of iron metabolism. The high frequency of iron deficiency at diagnosis raise the question of the use of IV iron as a frontline treatment of chemotherapy-associated anemia. A prospective, placebo-controlled, phase III trial is planned within our group, whose primary objective will be to demonstrate efficacy of ferric carboxymaltose alone compared to placebo as measured by the diminution of percentage of patients requiring red blood cell transfusion and/or ESA administration.No relevant conflicts of interest to declare.

There are some evidences that blood transfusions, either red blood cell (RBC) or platelet, could impact survival of patients affected with various medical conditions. Mechanisms are largely unknown but immune dysfunction, storage duration, cytokines or iron releases could be involved. These concerns led to the publication of revised guidelines with a more restrictive approach for RBC and platelet transfusions in various conditions, mostly surgery and emergency. However, less was known for cancer patients receiving therapy with a curative attempt.The phase III randomized LNH 03-6B protocol included elderly patients from 60 to 80-year with untreated diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index (aaIPI) of 1 or more. Patients were randomized between 8 cycles of R-CHOP given every 2 or 3 weeks (Delarue et al. Lancet Oncol 2013) and between a prophylactic treatment with Darbepoetin alfa in order to maintain hemoglobin level between 13 and 14 g/dL and an usual management of chemotherapy-induced anemia. In both arms, RBC and platelet transfusions were given according to physician decision without predefined threshold, but analysis of current practices showed that most patients were transfused with RBC for grade 3 or more anemia and with platelet for grade 4 thrombocytopenia.A total of 602 patients were included in the study and 599 have been analyzed for safety issues. Overall, 236 patients received at least one RBC transfusion (39%) with a higher incidence in the R-CHOP14 group (47% versus 31%, p=0.0001) and 60 patients (10%) received at least one platelet transfusion. Comparing with the whole study population, patients who were transfused presented with more aggressive baseline characteristics including percentage of patients with an aaIPI of 2 or 3 (72% versus 58%). Occurrence of RBC transfusion was associated with a worse outcome regarding progression-free (HR: 0.696, 95%CI: 0.547-0.885, p=0.0031) and overall survival (HR: 0.544, 95%CI: 0.414-0.714, p=<0.0001). Moreover, the number of episode of red blood cell transfusion (0 vs. 1-2 vs. >2) was also associated with PFS and OS. Occurrence of platelet transfusion was also associated with worse PFS (HR: 2.658, 95%CI: 1.922-3.677, p<0.0001) and OS (HR: 3.257, 95%CI: 2.302-4.608, p<0.0001), with an impact of the number of episode (0 vs. 1 vs. >1). In a multivariate analysis including LDH level, ECOG performans status and β2-microglobulin level, RBC and platelet transfusions were both predictive for overall survival (HR: 1.575, 95%CI: 1.158-2.143, p=0.0038 and HR: 2.608, 95% CI: 1.736-3.917, p<0.0001). Finally, no adverse event was associated with transfusion.In elderly patients who received a first line immunochemotherapy for aggressive B-cell lymphoma, occurrence of transfusions as well as the number of blood products transfused appear to be significantly and independently associated with lower survival rates. These results suggest a direct effect of transfusion and will prompt us to explore possible mechanistic explanations in animal models and to validate this hypothesis in others cancer populations.No relevant conflicts of interest to declare.

Anemia is a common feature at diagnosis of patients with lymphoid malignancies and has been previously described as an important prognostic factor (Moullet et al. Ann Oncol1998). Recent guidelines recommend evaluating iron parameters as part of the initial assessment of cancer associated anemia in order to propose iron therapy for patients with functional or absolute iron deficiency. However, incidence of iron parameters abnormalities and impact on prognosis is largely unknown.

MCL outcome has improved during the last decades. In its first randomized trial, the MCL net demonstrated that myeloablative consolidation followed by ASCT resulted in a significant prolongation of PFS in advanced stage MCL (Dreyling et al Blood 2005). Recent phase II studies suggest that the addition of rituximab and/or high dose ARA-C may significantly improve outcome. A phase II trial using sequential R-CHOP/R-DHAP followed by ASCT showed an ORR of 95% with a CR rate of 61%, a median EFS of 83m and a 75% survival rate at 5 years (Delarue et al Blood 20012). Two years ago we presented preliminary results of the the MCL randomized trial comparing 6 courses of CHOP plus Rituximab followed by myeloablative radiochemotherapy (12 Gray TBI, 2×60mg/kg Cyclophosphamide) and ASCT (control arm A) versus alternating courses of 3x CHOP and 3x DHAP plus Rituximab followed by a high dose ARA-C containing myeloablative regimen (10 Gray TBI, 4×1,5 g/m2 Ara-C, 140mg/m2 melphalan) and ASCT (experimental arm B) and have shown that after a follow up (FU) median of 27m patients of Arm B experienced a significantly better time to treatment failure (TTF) (49m vs NR; p=0.0384, HR 0.68), but no overall survival difference. Here, we present final results after a longer FU.Patient eligibility criteria included previously untreated MCL stage II-IV up to the age of 65 years. Histological diagnosis was confirmed by a central pathology review board. The primary end point TTF was monitored continuously by a sequential procedure based on a one sided triangular test. Stable diseases after induction, progression or death from any causes were considered as treatment failure. Sample size was calculated to detect a relative risk of 52% for arm B with a power of 95%. Randomization was stopped as soon as a significant difference was observed between the two arms.From July 2004 to May 2010, 497 patients were randomized in 4 countries (Germany, France, Poland, Belgium). The 455 patients evaluable for the primary analysis (19 no MCL, 13 not yet documented, 7 lost of follow up, 2 stage 1, and 1 R bendamustine chemotherapy) displayed the following characteristics (A vs B): median age 54 vs 56 year, male 79% vs 79%, stage IV 82% vs 81%, B symptoms 43% vs 31%, ECOG >2 4% vs 4%, elevated LDH 39% vs 35%, and MIPI low/int/high risk 60%/25%/15% vs 64%/23%/13%, respectively. After induction overall response (OR) was similar in both arms (90% vs 95%; p=0.19) but CR and CR/CRu rates were significantly higher in arm B (25% vs 36%; p=0.012 and 40% vs 54%; p=0.0003). The number of patients transplanted was similar in both arms (72% vs 73%). After transplantation OR and CR rates were comparable in both arms (98% vs 97% and 63% vs 61%). After a median FU of 51 months, TTF was longer in Arm B (46m vs 88m; p=0.0382, HR 0.68) mainly due to a lower number of relapses after CR/CRu/PR (n= 81 vs 40). The rate of ASCT-related death in remission was similar in both arms (4% vs 4%). Although CR rate after ASCT was similar in both arms, remission duration (RD) after ASCT was superior in Arm B (49m vs 84m; p=0.0001). At the time of final analysis, OS was superior in Arm B (NR vs 82m, p=0.045). Safety after induction was comparable in both arms except for an increased grade 3/4 hematological toxicity (Hb 9% vs 30%, WBC 50% vs 75%, platelets 10% vs 74%), renal toxicity (creatinine grade 1/2: 10% vs 44%, grade 3/4: none vs 1%), and grade 1/2 nausea and vomiting in arm B. Toxicities of both conditioning regimen were similar.With a longer FU, we confirmed that high dose ARA-C in addition to R-CHOP increases significantly complete response rates, TTF and in addition overall survival without clinically relevant increase of toxicity. Therefore, induction regimen containing high dose ARA-C followed by ASCT should become the new standard of care of MCL patients <65 y.Ribrag: Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; astrazeneca: Membership on an entity's Board of Directors or advisory committees; takeda: Membership on an entity's Board of Directors or advisory committees; bayer: Research Funding; sanofi: Research Funding. Gisselbrecht:roche: Consultancy, Research Funding; baxter: Research Funding.

Elderly patients with diffuse large B-cell lymphoma (DLBCL) frequently receive reduced dose-intensity (DI) chemotherapy (Lyman GH et al. J Clin Oncol 2004) but impact on outcome in the era of classical or dose-dense immunochemotherapy is unknown. Final results of the LNH03–6B did not show any difference in PFS (HR: 0.99 [95%CI: 0.78–1.26]; p=0.90) and OS (HR: 0.96 [95%CI: 0.73–1.26]; p=0.75) between R-CHOP14 and R-CHOP21 (Delarue et al. ASCO 2012).Patients between 60 and 80 years old with DLBCL and aaIPI≥1 were eligible. They were randomized between R-CHOP14 and R-CHOP21 for 8 cycles. Dose-intensity (DI) was calculated for all patients for cyclophosphamide (CPM), doxorubicin (DOX) and rituximab (RTX) and patients were separated into 4 quartiles for each of these drugs. Outcome (PFS and OS) according to final DI was evaluated for all patients and in R-CHOP14 and R-CHOP21 arms.602 pts were randomized, 600 were evaluable, 304 with R-CHOP14 and 296 with R-CHOP21. Median age was 70 years. Patient characteristics were similar in both arms. The percentage of cycles administered with G-CSF was 89% in R-CHOP14 and 66% in R-CHOP21. Median interval between 2 cycles was 14 d [9–94] in R-CHOP14 arm and 21 d [15–66] in R-CHOP21 arm. Median dose-intensity was 88% in R-CHOP14 and 97% in R-CHOP21 for CPM, and 88% in R-CHOP14 and 96% for R-CHOP21 for DOX. There was no difference of median dose-intensity for CPM and DOX according to G-CSF use at C1 in R-CHOP14 arm. In the R-CHOP14 arm, the increase of DI at the end of treatment, calculated according to 3-week interval as a reference, was 133% for CPM and DOX. When separating patients in 4 quartiles according to final dose intensity, there was no impact for CPM, DOX and RTX for the entire cohort in term of PFS and OS. Moreover, decreased DI for CPM, DOX and RTX did not impact negatively PFS and OS in patients randomized in the R-CHOP14 arm. On the other hand, for patients included in the R-CHOP21 arm, PFS was negatively impacted by lower DI of CPM (p=0.02), DOX (p=0.007) and RTX (p=0.006). OS was also negatively impacted by lower DI of CPM (p=0.0002), DOX (p<0.00001) and RTX (p<0.0001). In the R-CHOP21 arm, the negative impact was pronouncedly marked when comparing patients in the first and the second quartiles with those in the fourth quartile.While low DI has a major impact on PFS and OS in patients who receive conventional dose immunochemotherapy, consequences for patients receiving dose-dense immunochemotherapy seem less pronounced. As a consequence, immunochemotherapy could be safely decreased for elderly patients who receive R-CHOP14 and experienced adverse events.No relevant conflicts of interest to declare.

Genomic gains and losses play a crucial role in the development and progression of DLBCL and are closely related to gene expression profiles (GEP), including the germinal center B-cell like (GCB) and activated B-cell like (ABC) cell of origin (COO) molecular signatures. To identify new oncogenes or tumor suppressor genes (TSG) involved in DLBCL pathogenesis and to determine their prognostic values, an integrated analysis of high-resolution gene expression and copy number profiling was performed.Two hundred and eight adult patients with de novo CD20+ DLBCL enrolled in the prospective multicentric randomized LNH-03 GELA trials (LNH03-1B, -2B, -3B, 39B, -5B, -6B, -7B) with available frozen tumour samples, centralized reviewing and adequate DNA/RNA quality were selected. 116 patients were treated by Rituximab(R)-CHOP/R-miniCHOP and 92 patients were treated by the high dose (R)-ACVBP regimen dedicated to patients younger than 60 years (y) in frontline. Tumour samples were simultaneously analysed by high resolution comparative genomic hybridization (CGH, Agilent, 144K) and gene expression arrays (Affymetrix, U133+2). Minimal common regions (MCR), as defined by segments that affect the same chromosomal region in different cases, were delineated. Gene expression and MCR data sets were merged using Gene expression and dosage integrator algorithm (GEDI, Lenz et al. PNAS 2008) to identify new potential driver genes.A total of 1363 recurrent (defined by a penetrance > 5%) MCRs within the DLBCL data set, ranging in size from 386 bp, affecting a single gene, to more than 24 Mb were identified by CGH. Of these MCRs, 756 (55%) showed a significant association with gene expression: 396 (59%) gains, 354 (52%) single-copy deletions, and 6 (67%) homozygous deletions. By this integrated approach, in addition to previously reported genes (CDKN2A/2B, PTEN, DLEU2, TNFAIP3, B2M, CD58, TNFRSF14, FOXP1, REL…), several genes targeted by gene copy abnormalities with a dosage effect and potential physiopathological impact were identified, including genes with TSG activity involved in cell cycle (HACE1, CDKN2C) immune response (CD68, CD177, CD70, TNFSF9, IRAK2), DNA integrity (XRCC2, BRCA1, NCOR1, NF1, FHIT) or oncogenic functions (CD79b, PTPRT, MALT1, AUTS2, MCL1, PTTG1…) with distinct distribution according to COO signature.The CDKN2A/2B tumor suppressor locus (9p21) was deleted homozygously in 27% of cases and hemizygously in 9% of cases. Biallelic loss was observed in 49% of ABC DLBCL and in 10% of GCB DLBCL. This deletion was strongly correlated to age and associated to a limited number of additional genetic abnormalities including trisomy 3, 18 and short gains/losses of Chr. 1, 2, 19 regions (FDR < 0.01), allowing to identify genes that may have synergistic effects with CDKN2A/2B inactivation. With a median follow-up of 42.9 months, only CDKN2A/2B biallelic deletion strongly correlates (FDR p.value < 0.01) to a poor outcome in the entire cohort (4y PFS = 44% [32–61] respectively vs. 74% [66–82] for patients in germline configuration; 4y OS = 53% [39–72] vs 83% [76–90]). In a Cox proportional hazard prediction of the PFS, CDKN2A/2B deletion remains predictive (HR = 1.9 [1.1–3.2], p = 0.02) when combined with IPI (HR = 2.4 [1.4–4.1], p = 0.001) and GCB status (HR = 1.3 [0.8–2.3], p = 0.31). This difference remains predictive in the subgroup of patients treated by R-CHOP (4y PFS = 43% [29–63] vs. 66% [55–78], p=0.02), in patients treated by R-ACVBP (4y PFS = 49% [28–84] vs. 83% [74–92], p=0.003), and in GCB (4y PFS = 50% [27–93] vs. 81% [73–90], p=0.02), or ABC/unclassified (5y PFS = 42% [28–61] vs. 67% [55–82] p = 0.009) molecular subtypes (Figure 1).We report for the first time an integrated genetic analysis of a large cohort of DLBCL patients included in a prospective multicentric clinical trial program allowing identifying new potential driver genes with pathogenic impact. However CDKN2A/2B deletion constitutes the strongest and unique prognostic factor of chemoresistance to R-CHOP, regardless the COO signature, which is not overcome by a more intensified immunochemotherapy. Patients displaying this frequent genomic abnormality warrant new and dedicated therapeutic approaches.Salles: roche: Consultancy.

Abstract 151

Abstract 2723

Abstract 415This icon denotes a clinically relevant abstract

rituximab had dramatically improved the prognosis of patients with Diffuse Large B-cell Lymphoma (DLBCL) in combination with chemotherapy. Many biological and clinical studies suggested considerable inter-individual variability in term of anti-CD20 monoclonal antibody (mAb) activity with tumor and host-related influencing factors. Among host-related factors, the presence of functional polymorphisms in FcG receptors genes as FCGR3A-158V/F influences the affinity for IgG1 and consequently the antibody dependant cellular cytotoxicity (ADCC) with therapeutic mAbs such as rituximab. The clinical consequence reported to date consists in a better response rate to rituximab monotherapy for FCGR3A-158V homozygous patients treated for follicular lymphoma compared FCGR3A-158F carriers. In DLBCL and in the context of combination with chemotherapy, the role of FCGR3A and FCGR2A SNPs on treatment response and patient's outcome is not clear with few prospective studies. The aim of this study is to determine the impact of FCGR3A and FCGR2A SNPs on response and outcome of newly diagnosed DLBCL patients included in the prospective trials of the GELA (LNH2003 program).1564 patients from France, Switzerland and Belgium were included in the 5 prospective multicentric trials of the LNH2003 program of the GELA designed for DLBCL patients who were stratified in different subgroups based on age and International Prognostic Index (IPI) score. A sample of peripheral blood lymphocytes was collected before treatment from 760 patients who signed a specific consent form for this genetic study. After pathologic review and exclusion of patients not receiving rituximab (48 patients), 554 DLBCL patients were available for this study. SNPs were genotyped using a TaqMan® based assay.The median age of the 554 patients was 61 years (range, 18–93 years), 57% of them were male and 50% of patients presented at diagnosis a 2–3 age-adjusted IPI score. Chemotherapy regimen consisted in a combination of rituximab with CHOP-21 (110 patients, 20%), CHOP-14 (181 patients, 33%), low dose CHOP for patients older than 80 years (60 patients, 11%), or ACVBP regimen (203 patients, 36%). At the end of treatment, complete response (CR) or unconfirmed CR was observed in 75% of patients. After a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) was 70.2% and 75.7%, respectively. The distribution of the VV, VF and FF FCGR3A alleles was 14.8%, 46.4%, 38.8%, and 27.8%, 48.6%, 23.6% for HH, HR and RR FCGR2A alleles, respectively, and were therefore consistent with Hardy-Weinberg equilibrium. Initial clinical characteristics of patients (age, sex, Performance Status, stage, B-symptoms, number of extra-nodal sites, LDH level, IPI) were not different according to the two FCGR SNPs. CR/CRu after induction therapy was observed in 61%, 66%, 61% for VV, VF and FF carriers (P = .46) and 60%, 64%, 64% for HH, HR and RR carriers (P =.70), respectively. No difference of response after consolidation treatment was observed between each genotype of FCGR3A and FCGR2A SNPs. The 3-year PFS was 65.3%, 71.4%, 70.5% for FCGR3A VV, VF and FF carriers (P = .43) and 69.2%, 67.6%, 76.6% for FCGR2A HH, HR, RR carriers (P =.09), respectively. The 3-year OS was also not different between the three genotypes of each FCGR SNPs.To our knowledge, this is the largest prospective multicentric study that investigates the role of FCGR2A and FCGR3A SNPs on treatment response and outcome in a large series representing the whole spectrum of DLBCL patients. Based on these results, modification of rituximab schedule according to the FCGR3A and FCGR2A genotypes does not appear worth investigating. Others host-related factors influencing the efficiency of immunotherapy need to be investigate.No relevant conflicts of interest to declare.

Diffuse Large B-cell Lymphoma (DLBCL) is a heterogeneous disease based on biological analyses of tumor cells, with for instance the determination of two molecular subgroups, one with a profile close to germinal center B-cells and the second to activated B-cells. Data from the biology of tumor microenvironment could also be helpful to define different prognostic subgroups of DLBCL. The role of the biology of the patient with DLBCL, i.e. the host-related factors is little explored. Epidemiological studies showed that some inherited genetic variation in immune genes could increase the risk of lymphoma development and some retrospective studies indicated that patient's outcome could be predicted by some germ line polymorphisms (SNPs) in cytokine genes. The aim of this study is to determine the prognostic impact of 13 SNPs in 7 immune genes, IL10 (4 SNPs), Tumor Necrosis factor α (TNFA), lymphotoxin α (LTA), BAFF (3 SNPs), IL1A, IL8RB, IL4R (2 SNPs) in a cohort of newly diagnosed DLBCL patients included in the GELA LNH2003 prospective trials all treated by rituximab combined with chemotherapy.Patients and Methods: 1564 patients from France, Switzerland and Belgium were included in the 5 prospective multicentric trials of the LNH2003 program of the GELA designed for DLBCL patients who were stratified in different subgroups based on age and International Prognostic Index (IPI) score. A sample of peripheral blood lymphocytes was collected before treatment from 760 patients who signed a specific consent form for this genetic study. After pathologic review and exclusion of patients not receiving rituximab (48 patients), 554 DLBCL patients were available for this study. SNPs were genotyped using a TaqMan® based assay.The median age of the 554 patients was 61 years (range, 18–93 years), 57% of them were male and 50% of patients presented at diagnosis a 2–3 age-adjusted IPI score. Chemotherapy regimen consisted in a combination of rituximab with CHOP-21 (110 patients, 20%), CHOP-14 (181 patients, 33%), low dose CHOP for patients older than 80 years (60 patients, 11%), or ACVBP regimen (203 patients, 36%). At the end of treatment, complete response (CR) or unconfirmed CR was observed in 75% of patients. After a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) was 70.2% and 75.7%, respectively. All the polymorphism distributions of the SNPs analyzed were consistent with Hardy-Weinberg equilibrium. The main initial clinical characteristics of patients were not different according to the 13 studied SNPs, except for IL4R (rs2107356), CC carriers presented less frequently B symptoms than CT and TT carriers (28% vs. 41% and 61%, P = .01). No correlation was observed between the quality of the response at the end of the treatment and each genotype of the 13 studied SNPs. The 3-year PFS and OS were overall not influenced by the genotyping of the 13 SNPs. However, a trend for a better 3-year PFS for LTA +252GG carriers compared to LTA +252AG and AA carriers was observed (79.7% vs. 64.6% and 72.7%, P = .04).To our knowledge, this is the largest prospective multicentric study that investigates the role of immune SNPs on treatment response and outcome in a large cohort of newly diagnosed patients with DLBCL receiving rituximab. No correlation between SNPs and treatment response was observed. Analyses of the impact on outcome of each individual SNP showed only a trend for a prognostic role on PFS of LTA A252G SNP, which is already described as a functional SNP. The results will be further precise by the correlation of IL10, BAFF and TNFA /LTA full haplotypes with response and outcome.No relevant conflicts of interest to declare.

Abstract 90

Abstract 3676

Mantle Cell Lymphoma (MCL) has been characterized by poor long term prognosis with a median survival of only 3 to 4 years. However, outcome has improved during the last decades. In its first randomized trial, the MCL net demonstrated that myeloablative consolidation followed by ASCT resulted in a significant prolongation of PFS in advanced stage MCL (Dreyling et al Blood 2005). Recent phase II studies suggested that the addition of rituximab to CHOP like chemotherapy and/or high dose ARA-C may significantly improve remission rates and PFS. A French phase II trial using sequential R-CHOP/R-DHAP followed by ASCT showed an overall response rate of 95% with a CR rate of 61% translating into a median EFS of 83 months and a 75% survival rate at 5 years (Delarue et al ASH 2008).To evaluate the potential superiority of a high dose ARA-C containing regimen, the MCL net initiated a randomized trial comparing 6 courses of CHOP plus Rituximab followed by myeloablative radiochemotherapy (12 Gray TBI, 2×60mg/kg Cyclophosphamide) and ASCT (control arm A) versus alternating courses of 3x CHOP and 3x DHAP plus Rituximab followed by a high dose ARA-C containing myeloablative regimen (10 Gray TBI, 4×1,5 g/m2 Ara-C, 140mg/m2 melphalan) and ASCT (experimental arm B). Patient eligibility criteria included previously untreated MCL stage II-IV up to the age of 65 years. Histological diagnosis was confirmed by a central pathology review board. The primary end point time to treatment failure (TTF) was monitored continuously by a sequential procedure based on a one sided triangular test. Stable disease after induction, progression or death from any causes, were considered as treatment failure. Sample size was calculated to detect a hazard ratio of 52% for arm B with a power of 95%. Randomization was stopped as soon as a significant difference was observed between the two arms.From July 2004 to May 2010, 497 patients were randomized in 4 countries (Germany, France, Poland, Belgium). The 391 patients evaluable for the primary analysis (19 no MCL, 87 not yet documented) displayed similar characteristics in both treatment arms: median age 55 vs 56 years, male 78% vs 79%, stage IV 85% vs 79%, B symptoms 43% vs 33%, ECOG >2 5% vs 5%, elevated LDH 37% vs 38%, and MIPI low/int/high risk 61%/25%/14% vs 62%/23%/15%, respectively. After induction overall response was similarly high in both arms (A: 90% vs B: 94%; p=0.19) and CR rate and combined CR/CRu rate were significantly higher in arm B (26% vs 39%; p=0.012 and 41% vs 60%; p=0.0003). The number of patients transplanted was similar in both arms (72% vs 73%) and after transplantation overall response and CR rates were comparable in both arms (97% vs 97% and 63% vs 65%, respectively). After a median follow up of 27 months, patients in arm B experienced a significantly longer TTF (49 months vs NR; p=0.0384, hazard ratio 0.68) mainly due to a lower number of relapses after CR/CRu/PR (20% vs 10%), whereas the rate of ASCT-related deaths in remission was similar in both arms (3% vs 4%). Although CR rate after ASCT was comparable in both arms, remission duration (RD) after ASCT was superior in Arm B (48m vs NR; p=0.047). Interestingly, for patients in CR after ASCT, RD after ASCT was also presumably superior in arm B (51 months vs NR; p=0.077). At the time of analysis overall survival was similar in both arms with medians not reached and 79% vs. 80% survival rates at 3 years (p=0.74). Safety after induction was comparable in both arms except for an increased grade 3/4 hematological toxicity (Hb 8% vs 28%, WBC 48% vs 75%, platelets 9% vs 74%, respectively), an excess of renal toxicity (creatinine grade 1/2: 8% vs 38%, grade 3/4: none vs 2%), and more frequent grade 1/2 nausea and vomiting in arm B. Toxicities of both conditioning regimen were similar, except for higher grade 3/4 mucositis (43% vs. 61%) in Arm B, and higher grade 1/2 liver toxicity and constipation in Arm A.High dose ARA-C in addition to R-CHOP+ASCT increases significantly complete response rates and TTF without clinically relevant increase of toxicity. Therefore, induction regimen containing high dose ARA-C followed by ASCT should become the new standard of care of MCL patients up to 65 years.Walewski: Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stilgenbauer:Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Feugier:roche: Consultancy, Honoraria. Bosly:Roche: Membership on an entity's Board of Directors or advisory committees. Gisselbrecht:Roche: Research Funding.

Patients between 18 and 59y with DLBCL and aaIPI=1 were eligible. R-ACVBP consisted of 4 induction courses given every 2 weeks: rituximab (375 mg/m2) on d1, doxorubicin (75 mg/m2) on d1, cyclophosphamide (1200 mg/m2) on d1, vindesine (2mg/m2) on d1 and 5, bleomycin (10 mg) on d 1 and 5, prednisone (60 mg/m2) from d1 to d5, and intrathecal methotrexate (IT) (15 mg) on d2, G-CSF from d6 to d13. Patients then received a sequential consolidation therapy: 2 courses of methotrexate (3 g/m2) plus leucovorin rescue, 4 courses of rituximab (375 mg/m2), etoposide (300 mg/m2) and ifosfamide (1500 mg/m2) on d1, and 2 courses of cytosine-arabinoside (100 mg/m2, SC) for 4 days, each consolidation course being administered at a 14-day interval. Standard R-CHOP was delivered every 3 weeks for 8 cycles along with IT methotrexate at d1 of the first 4 cycles. The primary objective was to evaluate the efficacy of R-ACVBP compared to R-CHOP as measured by the event-free survival (EFS). Secondary endpoints were response rate, progression free survival (PFS), disease-free survival (DFS) for complete responders, overall survival, neuro-meningeal relapse rate and toxicities. Results are presented on an intend-to-treat basis. Response to treatment was evaluated according to 1999 Cheson criteria.From December 2003 to December 2008, 380 patients were randomized in 73 hematology/oncology departments of the GELA. One patient withdrew his consent the day of randomization and 379 received at least one day of study treatment, 196 with R-ACVBP and 183 with R-CHOP. Median age was 47y (18-59). Patient characteristics were well-balanced in terms of demography and baseline disease status: male gender, 59%; stage III-IV, 55%; elevated LDH, 44%; mass>10 cm, 22%; B symptoms, 28%; number of extra-nodal sites >1, 26%; bone marrow involvement, 13%. Overall response rate was 90.3% in the R-ACVBP group and 88.5% in the R-CHOP group (p=0.57). Complete remission rate (CR+CRu), was 82.7% for R-ACVBP and 80.3% for R-CHOP (p=0.56). At the time of this final analysis, in June 2010, the median follow-up was 44 months. The 3-year EFS was 80.9% (95% confidence interval (CI) 74.5–85.9) in the R-ACVBP group and 66.7% (CI 59.2–73.2) in the R-CHOP group (p=0.0035, hazard ratio (HR) 0.559). Significant differences were also observed for PFS (86.8% at 3 years (CI 80.9–91.0) vs 73.4% (CI 66.1–79.3), p=0.0015, HR 0.482), DFS (91.3% at 3 years (CI 85.1–95.0) vs 80.3% (CI 72.8–85.9), p=0.0019, HR 0.393) and overall survival (92.2% at 3 years (CI 87.1–95.3) vs 83.8% (CI 77.2–88.6), p=0.0071, HR 0.439). Patients in the R-ACVBP group experienced more frequently a serious adverse event (42% vs 15% in the R-CHOP group). Grade 3–4 hematological toxicity was more frequent in the R-ACVBP group, with a higher proportion of patients receiving red cell (51% vs 7% for R-CHOP) or platelet transfusions (13% vs 1%) and/or experiencing febrile neutropenia (39% vs 9%). There were 3 deaths (1.5%) attributed to toxicity of study treatment in the R-ACVBP group and 2 (1.1%) in the R-CHOP group.Compared to standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves EFS, PFS, DFS and overall survival with increased but manageable hematological toxicity in younger patients with DLBCL.Coiffier: Roche: Honoraria, Research Funding; Genentech: Research Funding. Gisselbrecht:Roche: Research Funding. Bosly:Roche: Membership on an entity's Board of Directors or advisory committees. Tilly:Amgen: Honoraria.

Zucca: Roche: Research Funding; Mundipharma: Honoraria, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Among indolent lymphomas, Rituximab is not specifically approved for MALT lymphoma but only for follicular lymphoma. Johnson:Roche: Membership on an entity's Board of Directors or advisory committees. Vitolo:Roche: Membership on an entity's Board of Directors or advisory committees. Coiffier:Roche: Research Funding. Morschhauser:Roche: Honoraria. Pettengell:Roche: Honoraria.

Abstract 432

Abstract 110

Abstract 109

Half of the cases of DLBCL occurs in patients over 65 years but very few data are available for patients over 80 years. These older patients however seem to respond as younger patients when treatment can be tolerated. In the aim to evaluate tolerance and efficacy of a reduced dosage chemotherapy regimen associated with rituximab in this population, the GELA initiated in 2005 a prospective, multicenter, phase II study.Patients older than 80 years with untreated CD20+ DLBCL, Ann Arbor stage I with bulky mass to IV and a performance status (PS) of 0 to 2 were eligible. Patients were treated with mini-CHOP chemotherapy (cyclophosphamide: 400 mg/m2 D1; doxorubicine: 25 mg/m2 D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m2 by oral route from D1 to D5) plus rituximab (375 mg/m2 D1) every 21 days for 6 cycles. GCSF was optional. The primary objective was to evaluate the efficacy of R-mini-CHOP as measured by the overall survival. Secondary endpoints were response rate, progression free survival (PFS), event-free survival (EFS), disease-free survival (DFS) for complete responders and toxicities. Survival results are presented on an intend-to-treat basis. Response to treatment was evaluated according to 1999 Cheson criteria.One-hundred-and-fifty-patients (51 male, 99 female) were included in 38 centers of the GELA. The median age was 84 years (range 80–95). Seventy-five percent of patients had a stage III/IV. LDH level was elevated in 69% of patients. Age-adjusted (aa) IPI was 2–3 in 66% of patients. One-hundred-twenty-nine patients completed the first three cycles and 108 received the whole regimen. The Dose-Intensity for patients who completed the three first cycle was 100% and 96.8% for doxorubicine and cyclophosphamide respectively. Thirty-six percent of patient received at least one injection of GCSF. The overall response rate was 74%, including 40% of complete response and 23% of unconfirmed complete response. At the time of this analysis, in July 2010, the median follow-up time was 20 months. The 2-year overall survival was 58.9% [95% CI: 49.3–67.2%]. The two-year estimated PFS, EFS and DFS were 47.4% [95% CI: 38.1–56.2%], 44.8% [95% CI : 35.7–53.6%] and 56.6% [95% CI : 49.3–67.2%] respectively. Hematological toxicity was the most common side effect. Grade 3–4 neutropenia was observed in 39% of the patients and grade 3–4 thrombocytopenia in 7%. Eleven patients (7%) experienced at least one episode of febrile neutropenia. Overall patients experienced a median of 4 nights of hospitalization during treatment phase (range 0–46).Thirty patients died during the treatment evenly distributed between treatment toxicity (6.7%) lymphoma (6.7%) and intercurrent causes (6.7%). In a univariate analysis, PS 0 or 1, aaIPI 0 or 1, number of extra-nodal sites <2, albumin level >35g/l, mass <10cm and a high IADL (Instrumental activities of daily living) score appear to be highly predictive of a prolonged survival. In a multivariate analysis a PS equal to 0 or 1 and an albumin level >35 g/l were significantly associated with a longer survival.In patients over 80 years with DLBCL and a good performance status, immunochemotherapy with R-mini-CHOP appears to be safe and effective, indicating that a substantial proportion of very old patients could indeed be cured. This regimen could be considered as a platform for the introduction of new drugs in the first line treatment of this population.No relevant conflicts of interest to declare.

Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma (FL). However, the optimal schedule, dose and precise activity of bortezomib in FL remain to be investigated.To evaluate the efficacy and tolerability of bortezomib in the treatment of advanced FL, but also using a qualitative comparison of two different dose schedules, based on safety, efficacy and dosing convenience to recommend a dose schedule for further clinical studies.This prospective, randomized, sequential, international, multicenter, 2-arm, non-comparative, open-label, clinical study was conducted from 08–2005 to 09–2008. The eligible subjects (follicular lymphoma grade 1–3, no CNS involvement, in relapse or refractory to previous therapy, ECOG 0–2, Absolute neutrophil count > 1000 cells/mL; Platelets > 50,000 cells/mL, Aspartate transaminase < 3 × ULN; Alanine transaminase < 3 × ULN; Total bilirubin < 2 × ULN; Creatinin level < 150 μmol/L, without known previous HIV serology) were randomized to receive either treatment in a 1:1 ratio. Treatment arm A patients (pts) received 1.5 mg/m2 bortezomib administered biweekly on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles. Treatment arm B pts received 1.6 mg/m2 bortezomib administered weekly on days 1, 8, 15, and 22 of a 35-day cycle for 6 cycles. Treatment allocation was stratified according to number of prior therapies (1 or 2 versus > 2) and time to progression (TPP) for the last given anti-lymphoma therapy (≤ 12 months versus > 12 months). Responses were assessed using 1999 IWG criteria. An interim analysis was planned after 15 evaluable pts randomized in each treatment arm; if only 5 subjects or fewer respond, the treatment arm was concluded to be ineffective and the treatment arm closed to inclusion; otherwise this treatment arm proceeded to include 50 pts.87 pts (51 [59%] men and 36 [41%] women) with median age of 65 years (range:40 to 77) were treated with bortezomib. Prior therapies were >2 in 62% and progression <12 months from last therapy in 49%. 30% previously received HDT with ASCT, and all of them were previously treated with immunotherapy. Arm B was closed to inclusion after interim analysis. After this interim analysis, the 6 patients still on therapy in this arm completed therapy according to arm A. 15/50 pts (32%) in arm A (bortezomib 1.5 mg/m2) and 8/37 pts (23%) in arm B (bortezomib 1.6 mg/m2) achieved a complete, unconfirmed complete or partial response at the end of treatment. Median duration of response was 16 (range 1–45) and 15 (1-39) months and PFS was 6 and 7.5 months for arms A and B, respectively. Most drug-related AEs (all grades, all cycles) were mild. AEs > grade 3 observed in more than 5% of pts were lymphopenia (25% both arms), thrombocytopenia (19% and 25% in arms A and B, respectively) and neutropenia (8% both arms). One pt died of possibly drug-related cardiac failure associated with hyponatremia.This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5 mg/m2 biweekly on a 21 days cycle in pts with recurrent or refractory FL. These results suggest recommending this dose schedule for further clinical study.Ribrag: LFB: Honoraria, Research Funding; servier: Research Funding; celgene: Research Funding; pfizer: Honoraria; novartis: Honoraria. Tilly:Amgen: Honoraria. Feugier:roche: Consultancy, Honoraria.

Abstract 853

Abstract 768

Treatment of primary CNS lymphoma (PCNSL) is based on high-dose methotrexate (HD-MTX) containing chemotherapy (CT) followed by brain radiotherapy (RT). Initial CT allowed 30% to 63% of complete response (CR) in recent large series. After CT, consolidation RT can increase the CR rate up to 80%. Despite this high rate of response after initial treatment, the outcome of patients remained poor. The impact of the quality of response on outcome is not well known as well as the outcome of PR patients who converted to CR after RT. We assessed these questions in patients with newly diagnosed PCNSL treated with HD-MTX-containing CT followed by RT in the prospective LNHCP93 GELA study.99 patients were treated in this prospective phase II study between 1995 and 2002. Patients younger than 61 years received C5R protocol (Blay et al. Blood 1995), Patients aged 61-70 years received reduced doses of C5R protocol and patients older than 70 years received a specific schedule with MTX, vepeside and cyclophosphamide. After CT, brain RT was planned: 20 Gy whole brain and a 36 Gy boost to the tumor bed. Responses after CT and after RT were evaluated by MacDonald criteria. Evaluation of response was made at time of the beginning of RT, 21-35 days after the last course of CT, and one month after the end of RT.Median age of the 99 PCNSL patients was 63 years (range, 20-82), 51% were male, 51% had performance status >1, and 58% had involvement of deep structures of brain. Forty-five patients were younger than 61 years, 36 were aged 61-70 years and 18 older than 70 years. After a median follow-up 83 months, median overall survival (OS) and progression-free survival (PFS) were 33 and 20 months, respectively. Seventeen patients (17%) died of acute toxicity during CT; 3 patients (3%) did not receive RT; 8 patients (8%) progressed or had stable disease after CT and 3 patients (3%) had no available data. Thus, 68 patients were assessable for this exploratory study with thirty-six patients (36%) in PR and 32 patients (32%) in CR after CT. Sixteen of PR patients converted to CR after RT (44% of PR patients after CT). Median OS of patients in CR and PR after CT was 80 and 34 months with a 5-year OS probability of 65% and 29%, respectively (p=0.02). Median PFS of patients in CR and PR after CT was 60 and 21 months with a 5-year PFS probability of 56% and 17%, respectively (p=0.03). In univariate and multivariate analysis, age and response were the two prognostic factors for OS but not performance status, number of tumors at diagnosis, site of tumor (involvement of deep structures). Only response to CT was predictive of PFS in multivariate analysis but not age, performance status, number of tumors, site of tumor at diagnosis. 5-year OS was 65% for CR patients before RT compared to 31% and 28% for PR patients who converted to CR after RT and for patients not in CR after RT, respectively (p=0.06). The 5-year PFS probability was 56% for CR patients before RT compared to 13% and 20% for patients who converted to CR after RT and those not in CR after RT, respectively (p=0.09).Despite the inherent bias of response analysis as a prognostic factor, this analysis of a prospective study of PCNSL patients showed that only patients achieving CR after CT may experience long term survival. This study also showed that PR patients who converted to CR after RT had a poor outcome, similar to patients that did not reach a CR after chemoradiotherapy.No relevant conflicts of interest to declare.

DLBCL CD 20+ in first relapse or pts refractory after first line therapy were randomized between R-DHAP and R-ICE. Response was evaluated according to Cheson Criteria (1999); chemosensitive patients after 3 cycles received BEAM and ASCT, and were randomized between observation and maintenance with rituximab for 1 yr. PET scan was not required at the time of design of the study but recommended, whenever possible. Consequently, the assessment of response with PET scan was also performed in a subset of patients and could be compared to revised Cheson criteria (2007).Intent to treat analysis was made on 394 pts ( 201 R ICE arm, 193 R DHAP arm) and was reported earlier this year (J Clin Oncol 27:15s, 2009 (suppl; abstr 8509). There was no difference between the two treatments arms. Prospectively, 123 pts with PET scans were recorded at the end of induction treatment and were reported by investigators positive or negative. Functional imaging was not used to modify treatment protocol. PET was negative ( FDG non-avid) in 61 pts and positive ( FDG-avid) in 62 pts; 60 and 58 pts completed 3 cycles of R-ICE or R-DHAP; 50 PET-ve and 26 PET +ve pts received BEAM respectively. Median age 54 yrs.; 52 relapses >12 months, 71 refractory/early relapses <12 months; 77 pts had prior exposure to rituximab; secondary IPI 0-1 77 pts, sIPI 2-3 40 pts. The overall response rate was 74%, with 47% complete remission. The number of CR, CRu, PR were 42,11,7 in PET negative pts and 1,4,26 in PET positive pts respectively. There was a highly significant difference (p<0.0001) in response rate per CT for PET negative 98% (CI 91-100%) vs. PET positive 50% (CI 37-63%) patients. Thus using updated criteria with PET, all the patients negative, except one stable, should be now characterized as complete responders. Whereas, only 5 pts PET positive were recorded to be in CR or CRu. No histology was available. For the whole population, three years EFS was 30%. EFS were different in pet negative pts 40% vs. 16% for positive pts ( p<0.0001). The same significant difference was found for PFS 43% vs. 28% respectively. Three years overall survival was 47%, for pts PET-ve 66% vs. pts PET+ve 49% ( p=0.007). For the 26 patients submitted to transplantation with PET positivity there was a significant difference for EFS (p=0.03) when compared to PET negative patients, but no statistical difference in PFS and OS. Factors affecting response rate in multivariate analysis were early relapse/refractory < 12 months and PET+ve following induction. The same factors were found in cox's model for EFS and PFS.This prospective study in relapsing DLBCL shows that PET scan is accurate to predict outcome. PET is an independent predictive factor with early relapse/refractory <12 months. A PET positivity pretransplantation is associated with a poor outcome and argues for new therapeutic approaches in this population.No relevant conflicts of interest to declare.

There are still controversies about the impact of erythropoiesis stimulating agents (ESA) on survival of patients with malignancies. The Groupe d'Etude des Lymphomes de l'Adulte (GELA) has conducted a multicentric prospective randomized phase III study to evaluate efficacy and safety of Darbepoetin alfa (DA) in elderly patients with DLBCL treated by immunochemotherapy. Here, we report the results of the planned interim analysis, held after the inclusion of the first 202 patients, with a median follow-up of 24 months.Patients and methods: Patients between 60 and 80 years old with DLBCL and aaIPI ≥ 1 were eligible. They were firstly randomized between two immunochemotherapy regimens combining Rituximab and CHOP given every 2 (R-CHOP14) or 3 weeks (R-CHOP21) for 8 cycles. They were subsequently randomized between an investigational arm with DA (Arm 1) given in order to maintain hemoglobin level between 13 and 15 g/dL and a conventional arm (Arm 2) with usual management of chemotherapy-induced anemia, including red blood cell transfusions and ESA according to usual practices. The objective was to evaluate the efficacy of DA in association with chemotherapy (R-CHOP) as measured by the EFS at 2 years, events being defined as death from any cause, relapse for complete responders and unconfirmed complete responders, progression during or after treatment and changes of therapy during allocated treatment. Secondary objectives were OS, PFS, DFS, response rate and analysis of toxicity.202 patients were included and 201 received study treatment ; 90 patients were randomized in DA group and 111 in conventional treatment group. Median age was 72 years. Patients' characteristics were similar in both arms with a slightly higher proportion of patients with aaIPI 2-3 in conventional arm : 68% compared to 56% (p=NS). Median hemoglobin (Hb) level at randomization was 12.2 g/dL. The median Hb level during treatment in DA arm was 11.9 g/dL and 10.7 g/dL in conventional arm respectively. Overall, 41 patients in conventional group received at least one dose of ESA during treatment. Eighteen percent of patients in DA group had at least one episode of Hb > 15 g/dL during treatment compared to 6% in conventional treatment group. Response rate (CR+CRu) after treatment was similar in both groups (69% in DA arm, 72% in conventional arm). Two-year EFS was 59% in DA arm compared with 49% in conventional arm (p=NS). A similar trend was observed for 2-year PFS (61% vs 51%), 2-year DFS (71% vs 56%) and 2-year OS (74% vs 63%) (p=NS for all). Grade 3-4 hematological toxicity was similar in the two groups. In contrast, proportion of patients receiving at least 1 red cell transfusion was higher in conventional arm (49% versus 36%). A total of 288 AEs were reported as serious (130 in DA group and 158 in symptomatic treatment group), concerning 122 patients (61%). Most SAEs were related to infectious complications. The rate of thromboembolic SAEs (composite criteria with pulmonary embolism, venous thrombosis from any site, coronary disease including myocardial infarction and cerebrovascular event) is slightly higher in DA group (13 SAEs) than in conventional arm (9 SAEs). Finally, the number of patients who died because of treatment toxicity was comparable in DA group (6 patients, 7%) and in conventional treatment group (7 patients, 6%).The results of interim analysis of the LNH 03-6B provide encouraging results about efficacy and safety of a prophylactic use of DA in this population. It should be confirmed by the final analysis of the LNH03-6B trial which is planned in 2010.No relevant conflicts of interest to declare.

Chemotherapy-induced anemia (CIA) is a complication of cancer therapy. Erythropoiesis Stimulating Agents (ESA) increase hemoglobin (Hb) concentration, if folate, vitamin B12 and iron levels are sufficient.This multicenter, prospective observational study explored response to darbepoetin alfa (DA) (Aranesp®) 500 μg Q3W or 300 μg Q2W in correlation with iron status in cancer patients with CIA. Secondary objectives were: safety and Hb outcome, Hb concentration at treatment initiation, and prescription behavior of physicians. All anemic patients foreseen to receive DA were enrolled in a registry. Data on baseline (BL) characteristics were collected. Subsequently, patients with normal vitamin B12 and folate were eligible for follow-up (FU).481 adult cancer patients with CIA (defined as Hb <11 g/dL as per EORTC guidelines (2007) and DA label at time of recruitment), treated in 26 oncology and hematology centers in Belgium and Luxemburg between December 2006 and April 2008, were enrolled in the registry. Mean ±SD age was 63.7±11.5 years; 42.5% of patients were male. Most patients (87.5%) had a solid tumor, mainly NSCLC, breast and colorectal cancer, and 54.4% were metastatic. DA treatment was initiated before the 4th cycle of chemotherapy in 82.5% of patients, planned to be synchronised with chemotherapy in 73.5% of patients and DA 500 μg Q3W was the most prescribed dose schedule (76.8%) in patients with solid and hematological tumors. Of the 481 enrolled subjects, 414 subjects were eligible for FU (396 subjects with available Hb data, and 379 subjects with available iron data). For patients with available Hb data (n=396), the mean ±SD Hb was 9.9±0.7 g/dL (range: 9.8-10) at inclusion and 10.9±1.7 g/dL (range: 10.7-11.1) at end of treatment. Hb target (≥11 g/dL) was reached by 87.4% (KM estimate; 95% CI: 81.2-92.3) of patients after a median time of 39.0 days (KM est.; 95%CI: 29.0-42.0). Iron deficiency was defined as having a Ferritin <100 ng/ml and/or TSAT <20% at inclusion or at any time on study. Of the 396 patients, 170 (42.9%) were iron deficient (ID) at inclusion. Hb target was achieved by 85.9% (KM est; 95%CI: 75.8-93.3) of patients with ID at inclusion vs 87.8% (KM est; 95%CI: 79.1-94.2) of patients without ID at inclusion. Among these iron deficient patients 20% received DA + iron. Hb target was reached more often (KM est: 100%) in these patients than in those not receiving iron treatment (KM est: 75.9%; 95% CI: 62.7-87.1) and the median time to target was also shorter (KM est: 28.5 days; 95% CI: 21.0-43.0) with iron than without (KM est: 42.0 days; 95% CI: 34.0-56.0). For patients with available iron FU data (n=379), the number of patients with ID at any time on study was 197 (52%). Thirty-six of these patients received DA + iron and reached Hb target after a median time of 28.5 days (KM est; 95% CI: 21.0-42.0) compared to 47.0 days (KM est; 95% CI: 35.0-62.0) for subjects not receiving iron. Among patients who were never iron-deficient during the study (101/379), 16 were given iron supplement and reached Hb target faster (KM est. median time: 21.0 days; 95% CI: 9.0-21.0, vs. 32.0 days; 95% CI: 21.0-55.0) than those not supplemented. The number of patients needing blood transfusion was similar regardless of iron deficiency at inclusion (KM est: 32.0% for ID vs. 35.5% for non ID). The DA treatment was safe: 5 patients reported moderate adverse drug reaction, none of them being serious.DA administered to cancer patients with CIA increased their Hb levels. Iron supplementation in iron deficient patients improved DA effectiveness although additional investigation is needed to draw any firm conclusions.Beguin: Amgen: Research Funding. Bosly:Amgen: Research Funding.

No relevant conflicts of interest to declare.

Abstract 101

Abstract 1701

Abstract 3741

Coiffier: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Gisselbrecht:Roche: Research Funding, Speakers Bureau. Bosly:Roche: Research Funding, Speakers Bureau. Herbrecht:Roche: Research Funding. Bouabdallah:Roche: Research Funding. Morel:Roche: Research Funding. Van Den Neste:Roche: Research Funding. Bordessoule:Roche: Research Funding. Haioun:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Tilly:Roche: Research Funding, Speakers Bureau. Salles:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Abstract 406This icon denotes an abstract that is clinically relevant.

Abstract 881