In patients with multiple myeloma (MM) not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), the 2 following options are recommended as part of front-line treatment and approved based on data from randomized phase III trials: melphalan/prednisone/thalidomide (MPT), or

8014 Background: Bortezomib (V) plus dexamethasone (D) is a treatment of choice of RRMM. In small series, the addition of an alkylator was beneficial. Bendamustine (B) showed a high activity in advanced MM. The IFM 2009-01 trial evaluates the combination of B, V and D in elderly pts with MM progressive on or after 1 st line therapy. Methods: We conducted a phase 2 trial combining B 70 mg/m 2 D1-8, V 1.3 mg/m 2 D1-8-15-22 and D 20 mg D1-8-15-22 every 28 days. 4 cycles were administered. In responders (PR or better), 2 additional cycles were provided followed by a maintenance phase with 6 cycles given every 2 months. Inclusion criteria were progression on or after 1 prior line of therapy, measurable disease, PS ECOG <3, ANC > 1.5x10 9 /l, platelets > 100x10 9 /l, creatinine < 250 mcmol/l, AST and ALT < 3xULN. Pts with prior exposure to bortezomib were excluded. Response was evaluated according to IMWG criteria. Primary end point was response at end of cycle 4, secondary objectives overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Results: The present analysis was restricted to the first 4 cycles. From 03/2010 to 07/2011, 73 pts were included, median age 75.8 years (range 66-86). Median time from diagnosis to inclusion was 29 months. All pts received only 1 prior therapy: MP in 12, MP-thalidomide in 44, lenalidomide-dexamethasone (LD) in 14, other in 3. 42 pts (57.5%) were responders at end of cycle 4 [CR: 8 (10.9%), VGPR: 9 (12.3%), PR: 25 (34.2%), SD: 10 (13.6%), progression: 11 (15%), early discontinuation: 10 (13.6%)]. 6pts/10 were in PR and 1pt/10 in VGPR at time of discontinuation. ORR was 67.1% (49/73 pts). 11 pts died (MM: 6, sepsis: 4, renal failure: 1). Adverse events grade 3-4 were neutropenia: 16 pts, thrombocytopenia: 7 pts, sepsis: 12 pts, gastro-intestinal: 8 pts, anaphylaxis: 1 pt. 2 pts had DVT. Peripheral neuropathy grade>1 occurred in 9 pts, all grade 2. Treatment was stopped in 20 pts (lack of efficacy: 11, toxicity: 9). Conclusions: These results compare favorably with those achieved with VD or LD. The triplet BVD combination is very effective and tolerable in elderly pts with MM in 1 st progression.

Haematodermic neoplasm is a recently recognized condition, characterized by tumour cells expressing CD4, CD56 and CD123. This phenotype is strongly suggestive of a plasmacytoid dendritic cell origin. This haematopoietic malignancy is a distinct clinicopathological condition with frequent skin involvement, an evolution toward leukaemia and a rapidly aggressive course. We report the case of a 64-year-old woman who presented with a haematodermic CD4+CD56+CD123+ neoplasm affecting the left cheek; the initial staging was otherwise negative. Despite this early stage of the disease, aggressive treatment including methotrexate-asparaginase and local radiotherapy was proposed as first-line therapy. Complete clinical remission was rapidly reached and the patient was still alive after > 30 months of follow-up. To date there is no consensus on the first-line treatment for such patients but intensive treatment is probably needed immediately even in cases of localized disease. The response obtained with CHOP (cyclophosphamide, doxyrubicin, vincristine, prednisone) or CHOP-like chemotherapy regimens is disappointing. Other regimens, such as those used in acute leukaemia, may improve the outcome of these patients.

The role of rituximab retreatment in relapsed B-cell lymphoma is not well known. We undertook a single center retrospective cohort study to investigate the efficacy of retreatment with rituximab with or without chemotherapy in patients with relapsed and refractory B-cell lymphomas. We only included patients treated first-line and in first progression; 178 patients were included in the study, of whom 29% had diffuse large B-cell lymphoma (DLBCL) and 28% had follicular lymphoma (FL). The overall response rate for the first treatment was 81% and for the second treatment was 66%. The median progression-free survival (PFS) for all patients from diagnosis was 13.2 months and from relapse was 12.5 months (not statistically different). For DLBCL the median PFS from diagnosis was 9.6 months and from relapse was 8.4 months, and for FL the median PFS from diagnosis was 26.4 months and from relapse was 19.2 months (not statistically different). The 5-year overall survival was 57%. In a historical comparison with rituximab-naive patients, rituximab-retreated patients had a shorter time to initial relapse than control patients, but there was no difference between the two groups for PFS from relapse. In conclusion, retreatment with rituximab, with or without chemotherapy, yields a high overall response rate in patients with relapsed and refractory B-cell lymphomas. Relapse occurring after rituximab-containing therapy appears to be more aggressive than that occurring after chemotherapy alone. The outcome of retreatment, in terms of progression-free survival, is similar to that of primary treatment.</.

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = -9% to 29%, P = 0.15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0.96, 95% CI = 0.41-2.2, P = 0.91] or overall survival (HR = 1.93, 95% CI = 0.39-9.58, P = 0.42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti-H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.

9535 Background: To study the change in post-treatment Quality of life (QOL) and fatigue in HL pts with favorable (H8-F) or unfavorable (H8-U) prognostic features (C Ferme et al, NEJM 2007;357:1916). Methods: In the H8-F, 3 MOPP-ABV plus involved-field radiotherapy (IFRT) were compared with subtotal nodal radiotherapy (STNI) alone. In the H8-U, 6 MOPP-ABV plus IFRT were compared with 4 MOPP-ABV plus IFRT and 4 MOPP-ABV plus STNI. Assessments were made using the EORTC QLQ-C30 (QOL) and the MFI-20 (Multidimensional Fatigue Inventory questionnaire). Questionnaires were given to pts in complete remission after end of treatment and at regular intervals for 5 years. Mixed models were used to assess reliable changes with time (0–6, 7–14, 15–21, 22–32, 33–47, ≥ 48 month). The impact of gender, age, prognostic group (H8-F vs H8-U), treatment arm and toxicity was also tested. Logistic regression on long term fatigue was performed to identify predictors among MFI-20 scales. Difference between countries were analyzed on Belgian, French and Dutch pts. P<0.01 was considered significant. Results: Of the 1,577 pts enrolled in the trial (median follow-up 92 months), 1,015 participated (4,877 forms). Improvement over time was observed for all scales except reduced motivation. Correlation was observed between: age and all scale changes except emotional functioning; gender (M

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10−7). We identified a subgroup of patients presenting at diagnosis with both low β2-microglobulin <4 mg/l and high hemoglobin (Hb) ⩾10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high β2-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

BACKGROUNDNon-Hodgkin's lymphoma (NHL) in patients older than 80 years is not a rare disease and treatment strategies are often difficult because of associated comorbidities.PATIENTS AND METHODSWe entered 205 NHL patients older than 80 years treated in a single institution in a retrospective analysis to describe clinical presentation and outcome and to identify specific prognostic factors.RESULTSThe median age was 83 years, and 91% of the cases were B-cell lymphomas consisting mainly of diffuse large B-cell lymphoma and marginal zone lymphoma. Among patients presenting comorbidities (87%), Charlson index was low in almost half of the patients (43%). Patients did not receive any treatment or received corticosteroids alone in 15%, surgery, radiotherapy, or monochemotherapy in 35%, polychemotherapy without anthracycline in 18%, and anthracycline based in 32%. Median overall survival was of 2.2 years. Main reason for death was disease progression (57%). Independent prognostic factors of survival were poor performance status (P < 10(-4)) and high lactate dehydrogenase level (P < 10(-5)). Comorbidities were not found to influence survival.CONCLUSIONSVery elderly NHL patients showed similar features and prognostic factors than younger patients. Death was related mainly to the disease, meaning that these patients should be more frequently treated with standard treatments.

BACKGROUND. The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphomaMETHODS. This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment. Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total body irradiation in 26 patients (77%).RESULTS. After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 106/kg. Three months after transplantation, 24 patients (71%) were in CR, and 7 patients (21%) were in PR. At 3 years from the day of transplantation, the estimated overall survival was 87%. With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years. Rituximab treatment before harvest did not delay hernatopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days.CONCLUSIONS. Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities.

Alemtuzumab has an impressive clinical activity in B-cell chronic lymphocytic leukemia. The standard regimen (30 mg three times weekly for 12 weeks) results in high rate of early responses but frequent early progression. To prolong TTP, we realized a phase II study with an identical initial scheme: 3, 10, 30 mg of Campath-1H on sequential days, followed by 30 mg three times weekly until partial response, and maintenance therapy with 30 mg every one or 2 weeks, then, 30 mg monthly until progression or toxicity. Between January 2001 and August 2005, 16 B-CLL patients have been treated with this regimen and were retrospectively analyzed on an intent-to-treat basis. Eighty-one percent (13/16) of the patients had received 3 or more prior chemotherapy regimens. Response was evaluated at 12 weeks (W12) after the beginning of the treatment by the CLL WG criteria. Survivals were defined from the first day of alemtuzumab. With a median follow-up for alive patients at 26 months, median duration of treatment was 8.5 months (range: 1.5–23.5) corresponding to a median number of 18 injections of alemtuzumab (range 6–36) realized. Nine (56%) patients received more than 6 months of monthly injections. Among them, 3 patients received one injection every 2 or 3 months after these 6 months. Two patients progressed in blood during maintenance. Modulation of the doses was then proposed with more frequent injections during a time period allowing to re-obtain a CR. Maintenance was stopped because of nodal progression in 6 patients, opportunistic infections in 2 patients (1HSV and 1 pulmonary infection), persistent CR in 3 patients, and persistant neutropenia in 1 patient. Objective response at W12 was reached in 13 (81%) of the patients, including 5 (31%) CR and 8 (50%) PR. One patient had a stable disease (disappearance of blood infiltration but stability of lymph nodes involvement) and 2 a progressive disease. Median duration of response was 11.7 months (range: 5–30). Median of TTP and overall survival were 12 months and 38 months, respectively. In this series, patients did not experience more hematological toxicities or opportunistic infections than reported with the standard regimen. Of the 13 patients that progressed at the time of analysis, 7 were re-treated by alemtuzumab (n=4) or alemtuzumab + chemotherapy (n=3). Objective responses were obtained in 6 patients during a median time at 8.7 months. In conclusion, maintenance alemtuzumab with modulation of dose intensity allowed improving time to progression and survival, without adding hematological toxicities and infectious complications.