ALBERT

Beschreibung: Abstract 4310 Purpose: Relapse remains the main issue after allogeneic stem cell transplantation (Allo-SCT) in high risk Multiple Myeloma (MM) patients. The aim of this study is to assess the anti-myeloma effect of lenalidomide followed by donor lymphocyte infusion (DLI) as adoptive immunotherapy after transplantation. Patients and methods: Twelve patients with refractory and high risk myeloma were analyzed. Median age at transplantation was 56 years (46–64); 6 patients (50%) received lenalidomide before Allo-SCT. All patients received a RIC including Fludarabine 30 mg/m2 5 days, ATG 2,5 mg/kg for 2 days and Busilvex 3.2 mg/kg/day (3 days in 6 patients and 2 days in 6 patients). All but one received peripheral blood stem cells (PBSC). Donor was HLA id in 6 patients and matched unrelated in 6 patients. It is our standard long term practice to consider post-transplant DLI in patients with progressive or persistent disease after day 100 if no GVHD signs were evident. In 2010, we introduced the use of lenalidomide after day 100 in patients with MM presenting the same characteristics. Doses ranged from 10 to 25 mg/day. Lenalodomide treatment could be completed with DLI, administered afterward, at least after 2 cycles. Results: The median time between Allo-SCT and lenalidomide was 10 months (3–38). The median initial dose of lenalidomide was 15 mg (10–25). Patients received a median of 6 cycles (1–10). Nine patients (60%) received an escalating dose of DLI; 1 × 107/Kg of CD3+cells for the first DLI and 1 × 108/Kg of CD3+cells for the second DLI. One patient with GVHD (after tapering of the cyclosporine A and only after 10 days of lenalidomide) and two patients with progressive disease after lenalidomide did not receive DLI. The toxicity related to lenalidomide was mainly haematological (grade II in 4 patients (33%) and grade I in 3 patients (25%); 7 patients (58%) had moderate asthenia. One patient developed a reversible renal insufficiency after 10 cycles of lenalidomide, none of our patients developed thrombo-embolism under treatment. At the last follow up, 9 patients are alive and all of them are under ongoing treatment. Four patients achieved complete remission (CR) and five patients partial remission at last evaluation. The 1 and 2 years probability of the progression-free survival (PFS) was 75% and 50% and overall survival (OS) was 83 % and 69% respectively. The median OS was not reached and the median PFS was 23 months. Conclusions: These data show that lenalidomide has an acceptable toxicity. Combination with DLI should be further evaluated in a larger cohort of patients. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 2693 Introduction: Treatment of Diffuse Large B-Cell Lymphoma (B-DLCL) is not well coded in the elderly patients. They may receive full dose immunochemotherapy, low dose chemotherapy or palliative treatment regarding co morbidities, Performans Status (PS), psychological, social or mental state. The lack of age-adapted prognosis factors including geriatric scales induce a subjective choice for the treatment. The purpose of the study is to evaluate the outcome of all the patients treated in a single institute for a B-DLCL, with comparison of age of diagnosis and treatment received. Methods: All patients with B-DLCL, age≥70 years, treated in the Paoli-Calmettes institute between 1995 and 2008 were included, excepted patients with intra-ocular and cerebral localizations or with a “Burkitt-like” histology. Were also excluded patients with incomplete data. Treatments were simplified for statistic analysis in three types: CHOP Like (CH-L): three chemotherapies with anthracyclin (or etoposide in place if cardiac impossibility) with conventional doses, mini-CHOP-Like (mCH-L): with reduce doses of anthracyclin and cyclophosphamide, or COP Like (C-L): two agents without anthracyclin. Factors studied in the different items are systematically Age (70–79 vs olders), PS (0–1 vs 2–4), LDH, Ann Arbor stage (AA:1–2 vs 3–4) and type of chemotherapy. Results: From 1995 to 2008, 212 patients with B-DLCL were admitted in the Paoli-Calmettes institute for a B-DLCL. The median age was 76 years [range 70–90], 70% of the patients had a PS=0–1 and 30% a PS=2–4, LDH was increased in 55% of patients, AA was 3–4 in 58% of cases. The repartition of chemotherapy was 56% for CH-L, 33% for mCH-L and 11% for C-L. In the 70–79 age subgroup, CH-L is predominant (67% vs 25% for the older patients, p

Beschreibung: Abstract 5190 Limited data is available concerning feasibility and efficacy of high dose therapy (HDT) supported by autologous PBSCT in elderly patients with non-Hodgkin lymphoma (NHL). In young patients with poor prognostic features intensification supported by PBSCT as a part of first-line treatment suggests survival benefit. It is not clear if the same strategy is applicable to the older patients. The Institute Paoli-Calmettes database was reviewed for all DLBCL patients who received BEAM followed by PBSCT in patients 〉=60 years old between January 1998 and January 2010 (13 years). All patients were HIV-negative and received BEAM intensification as a part of front-line treatment. All of them were in a complete response after CHOP or R-CHOP induction prior to autograft. Thirty six auto-transplanted patients were identified (median age 63 y, range 60–68). This cohort was compared with closely matched group of 43 patients of same age range, who received first-line CHOP or R-CHOP regimen without intensification in the same 13-year interval. Only patients in a complete response after first line were included. As frontline autoPBSCT was performed in high-risk patients, the group without HDT was naturally privileged in the terms of Ann-Arbor stage and aaIPI index. There was significant difference in the localised vs disseminated disease (stage I-II: 53,4% in no-HDT vs 14% in HDT group, p=0,00025) and aaIPI (0-1: 72% in no-HDT vs 28% in HDT, p=0,000086) between the two groups. Factors evaluated included treatment-related mortality (TRM), overall survival (OS) and event-free survival (EFS). There were no transplant-related deaths in the HDT group. The estimated 5-year OS was 81,3% (95% CI 62,5-91,9 %) and 10-year OS was 65% (95%CI 34,2-86,9%) for HDT group compared to 91,5% (95% CI 77,5-97,1%) and 58,4% (95% CI 20–88,8%) in the no-HDT group (p=NS). There were 8 events (6 relapses and 2 secondary malignancy deaths) in the HDT group and 11 events (9 relapses and 2 secondary malignancy deaths) in no-HDT (5-year EFS 77,6% (95% CI 60,3-88,8%) vs 78,3% (95%CI 62,3-88,8%), p=NS)). We conclude that front-line autologous PBSCT with BEAM conditioning can be safely performed in patients aged 60 years or above with DLBCL after CHOP of R-CHOP induction. There was no difference in OS and EFS between cohorts with and without intensification even if the auto-transplantation procedure was reserved for the high risk patients only. The first-line HDT with autologous PBSCT in older patients with high-risk IPI score might improve survival in this group and produce results similar to those in the low-risk group. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 4989 Data emerging from initial clinical trials demonstrated that Lenalidomide has a significant activity against different subtypes of aggressive B-cell lymphoma. Clinical responses are histologic subtype-dependent and most prominent in mantle cell lymphoma. The results in DLBCL were less encouraging with ORR of 26%, CR of 9%, PFS of 2.7 mo. Concurrently targeting the tumor cell itself with monoclonal antibody and targeting the immune response and microenvironment with Lenalidomide may be a promising therapeutic strategy. By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with rituximab resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma. Recently the combination Lenalidomide-Rituximab (LR) was shown to be highly efficacious in follicular NHL. Encouraging by our initial results of LR combination in patient with refractory (R/R) DLBCL (Leuk Lymphoma 2010), Institutional Multidisciplinary Meeting proposed this combination for other 8 patients with R/R DLBCL. All patients were refractory to three or more previous lines of conventional immuno-chemotherapy. All except 3 primary-refractory pts were previously autografted. Patients received combination of Rituximab 375 mg/m2, day 1 or day 7; Lenalidomide (Revlimid), 15 mg/d for the first pt and 25 mg/d for other 8 pts, for 21 days. Dexamethasone 40mg, day 1–4 was given for first 6 pts. Initial decision on adding Dexamethasone was based on the extrapolation from the recommended regimen used in multiple myeloma, but it was abandoned in last 3 pts. Of 9 pts enrolled on study, 8 received 〉 2 cycles of LR and all of them were evaluable for response. Median age for evaluable pts was 52 (range: 19–73), 3 pts are female. Of 8 evaluable pts, 5 (63%) responded to LR, including 3 pts (38%) with CR and 2 (25%) patients with PR. These two PR pts were primary refractory to chemotherapy before LR and both were grafted (1 auto and 1 allo) after three courses of LR. One pt with clinical and PET-FDG scan improvement after 3 courses of LR was included into “auto-allo” tandem program and actually in CR after PBSCT. Two pts progressed on LR treatment and were switched to palliative regimens. As regards the follow-up, 3 pts in CR are evaluable for evaluation. Two pts received 6 and one pt 8 courses of RL treatment. One patient relapsed after 24 mo of CR and other 2 patients are in CR at +11 and +6 months. In relapsed/refractory DLBCL modest initial results of lenalidomide monotherapy emerge the use of new effective combinations. Recently several phase II studies of LR efficacy in indolent NHL were proposed. For instance, there is no published data of long-term safety and efficacy of this combination in DLBCL. Given the poor prognosis of refractory DLBCL, enrolment in already running prospective clinical trials with lenalidomide are underway and the investigation of the combination of Lenalidomide and Rituximab is further warranted. Disclosures: No relevant conflicts of interest to declare.