ALBERT

Description: Twenty four patients (pts) with planned autologous stem cell transplantation for lymphoma diseases (Hodgkin’s disease=4; non-Hodgkin’s lymphoma=20) received chemotherapy (CT) (Induction CT=3 and salvage regimen= 21) followed by a fixed single dose (6 mg) administration of Pegfilgrastim (PF) after the last day of CT for peripheral blood stem cell collection (PBSC) (target cell dose of 3 2×106 CD34+/kg). Median age was 53 yrs (24–68) and median weight was 72, 5 kg (45–98). Among the 24 pts, 7 received more than 2 lines of CT regimens. The injection of PF was well tolerated. Median time interval between day 1(D1) of the cycle of CT mobilization and first leukapheresis session was 14 days (10–18) while the median time interval between injection of PF and first leukapheresis session was 9 days (6–13). Stem cell collection was started when the absolute number of circulating CD34+ cells was 〉10×106/L and performed with standard volume leukapheresis. Median CD34+ cells level at D1 of leukapheresis was 35, 5/mm3 (11–320) and interestingly, more than 35 % of pts could reach this median level of CD34+ early after PF injection (around D6). Notably, 22 pts reached the target cell dose in 2 sessions of leukapheresis or less (10 pts after 1 session, 10 other pts after 2 sessions, 2 pts after 3 and 4 sessions respectively). The median number of leukapheresis sessions was 2(1–4) and the median CD34+ cells harvested was 4×106/kg (0,8–26,6). Two pts (DLBCL = 1 and FL = 1) could not reach the level of CD34+ required to start leukapheresis and both became secondary refractory to CT. In univariate analysis, PBSC collection of 〉 4×106/kg was highly correlated with pts who started their collection at D9 of PF administration (P=0,01) and with those presenting a CD34+ cells level 〉 35.5/mm3 at D1 of leukapheresis (P=0,033). White blood cells level higher than 9 G/l was also predictive of circulating CD34+ cells 〉35,5/mm3 (P=0,033). These data suggest that PF may represent an attractive option for PBSC mobilization particularly for pts with lymphoma when optimal compliance of frequent sequential regimens of CT is required. We also emphasize that stem cell mobilization is effective even in pts in second or subsequent salvage CT regimen. Importantly, the circulating CD34+ count should be performed from D6 of PF administration. The presentation will include the updated data.

Description: Introduction: Median age of Chronic Lymphocytic Leukemia (CLL) patients is 72 years with 40% older than 75 and 22.8% over 80 years. Important therapeutic progresses have been made, including chemo-immunotherapy as well as the recent use of targeted therapies, leading to progression-free-survival (PFS) and overall survival (OS) improvements. Although the elderly represents the largest subgroup of CLL patients, they are underrepresented in clinical studies and little is known about their clinical characteristics, treatment and outcome. Consequently, results from trials cannot be directly translated into clinical practice for these patients. Bairey et al (Ann Hematol, 2011) reported a series of 214 patients (80 years or older) diagnosed in Israel between 1979 and 2009 with a mean age of 84. However, in this cohort, 56% of the patients had a Rai stage 0 and only 53 received treatment. Median survival was 56 months. Methods: We performed a retrospective study of CLL patients aged 80 or more at initiation of first line therapy. Patients were treated between 2003 and 2013, in 17 hospitals affiliated to the French Innovative Leukemia Organisation (FILO). We report here a cohort of 201 such CLL patients, and describe their clinical and biological characteristics, treatment options and outcome. Results: Patients' median age was 83.4 years (80-92), 29% were older than 85 years, and the sex ratio was 60% male/40% female. Performance status (97%≤ 2) and nutritional status (median Corporal Mass Index of 25.3 kg/m²) were preserved. The median Cumulative Index Rating Scale (CIRS) comorbidity score was 5. More precisely in term of fitness, 57.8% patients were characterized as "go-go" with a CIRS ≤ 6 and organ comorbidities 3, and CD38 was positive in 43,4% of the 129 cases tested (64%). Cytogenetic data were available for 42% of the patients. Isolated abnormalities were deletion 13q (38.1%), trisomy 12 (21.4%), deletion 17q (10.7%) or deletion 11q (7.1%). Besides, associated chromosomic abnormalities were detected, mainly by fluorescence in situ hybridization (FISH) and complex karyotypes (1.2%). At treatment initiation, Binet stage was either A (27.2%), B (28.7%) or C (41.5%). Therapies consisted mainly in Chlorambucil (65.5%), Bendamustine (10.5%) and Rituximab (44.3%). Indeed, therapy regimens were composed of Chlorambucil alone (45.3%) or chemo-immunotherapy (48.3%) including Rituximab+Chlorambucil (22.7%), Rituximab+Bendamustine (10.4%), Rituximab+Cyclophosphamide+Dexamethasone (5.5%) or Rituximab+Fludarabine+Cyclophosphamide (5.5%). In term of tolerance, 20.2% of the patients required hospitalization and 10% of these cases were febrile neutropenia. Finally, 31.8% required a dose reduction of chemotherapy. The Overall Response Rate was 65.9% with 31.4% of clinical complete remission. The median OS and PFS (from treatment initiation) were 48.6 and 18 months, respectively (cf. Survival curves). Afterwards, an important number of patients (41.3%) remained fit enough to receive a second line treatment. In univariate analysis, only comorbidities evaluated by the CIRS had a significant impact on survival (p=0.03). Indeed patients identified as fit by a CIRS score ≤ 6 and no organ comorbidity 〉 3 had a better outcome. Conclusion: We report a large series of elderly CLL patients, who received first line treatment at a median age of 83. Median OS was about 4 years, which is less than normal population of the same age. Our results suggest that treatment (including immunochemotherapy) is feasible, even in this very old population. Different bias are possible in this retrospective study including the selection of only fit patients, the low percentage of geriatric evaluation, and the possible undertreatment of this population since chlorambucil was the most frequent treatment. In the future, prospective trials should target this population. Oncogeriatric evaluation and new targeted therapies should be part of such future trials. Figure 1. Survival curve 1: Overall Survival Figure 1. Survival curve 1: Overall Survival Figure 2. Survival curve 2: Progression Free Survival Figure 2. Survival curve 2: Progression Free Survival Disclosures Dupuis: ROCHE: Speakers Bureau; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Aurran-Schleinitz:CSLBehring: Honoraria; Janssen: Honoraria. Cymbalista:Karyopharm: Honoraria; Gilead: Honoraria; Roche: Honoraria; Janssen: Honoraria, Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Cazin:GILEAD,: Honoraria; ROCHE: Consultancy; MUNDIPHARMA: Honoraria, Research Funding; NOVARTIS: Honoraria. Leblond:Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Cartron:Sanofi: Honoraria; Gilead: Honoraria; Celgene: Honoraria; GSK: Honoraria; Roche: Consultancy, Honoraria.

Description: Abstract 4507 Bronchiolitis obliterans (BO) is a late-onset pulmonary complication occurring after stem cell transplantation as a manifestation of chronic graft versus host disease (cGVHD). It is characterized by an insidious airflow obstruction leading to a high mortality. To identify risk factors of BO, we retrospectively analyzed 151 allogeneic bone marrow recipients allografted between 2006 and 2008 in our hematology center. The median age is 47 years (4 – 66 years). The ratio male/female is 2. 52 % of patients were allografted for AL, 13% for myelodysplastic syndrome, 10.5% for NHL, 3 % for CML, 4.6% for CLL, 4% for HL. Sixty four patients (42%) had a myeloablative conditioning regimen and 87 patients (58%) had reduced intensity conditioning regimen. Busulfan was used as a part of the conditioning in 45% of the transplantations and total body irradiation in 47%. The source of the graft is bone marrow in 32% of cases, peripheral stem cells in 57% of cases and umbilical cord blood in 11% of cases. In 50 % of the cases the donor is a sibling. GVHD prophylaxis is cyclosporine associated with MTX in 41% of the cases, cyclosporine alone in 25% of cases and cyclosporine with MMF in 30% of the cases. Patients had pulmonary function test pre transplant and at 3, 6, 12 months after transplantation and then every 6 months. BO was defined according to national institute of health (NIH) consensus for diagnosis and staging of cGVHD. NIH definition requires: absence of active infection, decreased FEV1 (

Description: Introduction Ibrutinib is a first-in-class, once-daily, oral, covalent inhibitor of BTK that has excellent single-agent activity in patients with previously treated CLL/SLL, based on results of published clinical studies. In the HELIOS trial, addition of ibrutinib to BR resulted in an 80% reduction in disease progression or death and confirmed for the first time, in a randomized setting, the benefit of ibrutinib-based therapy compared with standard chemoimmunotherapy (CIT) in previously treated patients (Chanan-Khan et al. ASCO 2015). In patients with CLL or SLL, deletion 17p (del17p) and 11q (del11q), complex karyotype, unmutated IgVH, and elevated ZAP70 are known high-risk prognostic factors. The current analysis reports on the efficacy of ibrutinib + BR vs placebo + BR in patients in the HELIOS trial with relevant high-risk biomarkers. Methods HELIOS is a randomized, double-blind, placebo-controlled, phase 3 study. Patients with active CLL/SLL following ≥ 1 prior therapy were randomized 1:1 to receive BR (≤ 6 cycles) with either ibrutinib (420 mg daily) (n = 289) or placebo (n = 289). Patients with del17p (〉 20% of cells) were excluded. Ninety patients in the placebo arm with independent review committee (IRC)-confirmed progressive disease crossed over to ibrutinib, per protocol amendment. The primary end point was IRC-assessed progression-free survival (PFS), and overall survival (OS) was a secondary end point. A total of 287 patients in each arm had data available for at least 1 biomarker, and this population was used for the biomarker analyses. Correlation of biological risk factors at baseline with PFS and OS was analyzed using Kaplan-Meier analysis and curves compared using log-rank tests. Hazard ratios (HRs) were estimated using univariate Cox proportional hazards models. Results At a median follow-up of 17 months, IRC-assessed PFS was significantly longer with ibrutinib + BR vs placebo + BR in the overall study population (median not reached vs 13.3 months, respectively; HR: 0.203; 95% CI: 0.150-0.276; p 〈 0.0001). All subgroups of patients, including those with adverse prognostic parameters, e.g., del11q, complex karyotype, unmutated IgVH and elevated ZAP70 levels, had a significantly longer PFS with the addition of ibrutinib to BR as compared with placebo + BR (Table 1). As expected, each of these adverse prognostic parameters had a negative impact on PFS in the placebo + BR arm, e.g., the median PFS was shortest in patients with complex karyotype [8.5 months vs 13.8 months in patients without complex karyotype] and in patients with unmutated IgVH (11.3 months vs 22.1 months in patients with mutated IgVH). Interestingly, in the ibrutinib + BR arm, the adverse impact of these risk factors could not be detected (median PFS not reached irrespective of presence of risk factors). For example, in Figure 1 showing the PFS curves stratified by both del11q status and treatment, the outcome for patients in the ibrutinib + BR arm with del11q was similar to those without, with a trend toward better outcome in the del11q patients (e.g., longer PFS - not reached vs 24.9 months), unlike for patients in the placebo + BR arm (11.01 months vs 13.86 months). In patients with del11q, unmutated IgVH, or elevated ZAP70, there were also statistically significant benefits in OS for those receiving ibrutinib + BR vs placebo + BR (del11q: HR: 0.326, 95% confidence interval [CI], 0.122-0.870; p = 0.025; unmutated IgVH: HR: 0.515, 95% CI, 0.298-0.890: p = 0.017; elevated ZAP70, HR 0.536, 95% CI, 0.289-0.994: p = 0.048). Addition of ibrutinib also increased PFS in patient subgroups with other cytogenetic or clinical prognostic markers (such as del13q or bulky disease) compared with placebo. Conclusions All subgroups of patients, irrespective of adverse risk factors, such as del11q, complex karyotype, elevated ZAP70, and unmutated IgVH, benefit from the addition of ibrutinib to BR compared with placebo + BR. The negative impact of these known risk factors is apparent in patients in the placebo + BR arm, but is not seen in patients in the ibrutinib + BR arm. These results suggest that ibrutinib + BR is a suitable treatment regimen for all patients with previously treated CLL/SLL, including those with high-risk prognostic markers. Disclosures Cramer: Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau; Mundipharma: Other: Travel grant; Glaxo Smith Klein/Novartis: Research Funding; Astellas: Other: Travel grant; Gilead: Other: Travel grant, Research Funding. Fraser:Janssen: Honoraria, Research Funding, Speakers Bureau; Hoffman LaRoche: Consultancy, Honoraria; Celgene: Honoraria, Research Funding. Santucci Silva:Janssen: Other: Travel reimbursement, Research Funding; GSK: Research Funding; Celgene: Research Funding; Merck: Research Funding; Novartis: Other: Travel reimbursement; Hoffman LaRoche: Other: Travel reimbursement, Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Goy:Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Mato:Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Other: Travel, Accommodations, Expenses; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: Travel, Accommodations, Expenses; TA Therapeutics: Research Funding. Damle:Janssen: Employment. Phelps:Janssen/J&J: Employment, Equity Ownership. Mahler:Janssen: Employment, Other: Travel reimbursement. Salman:Janssen/J&J: Employment, Equity Ownership. Schaffer:Janssen: Employment. Howes:Janssen/J&J: Employment, Equity Ownership. Balasubramanian:Pharmacyclics LLC, an AbbVie Company: Equity Ownership; Janssen: Employment, Equity Ownership.

Description: Abstract 3528 Allogeneic stem cells transplant (allo-SCT) is currently the preferred therapeutic option for young adults with Ph- ALL in first CR. However, the results of different studies suggested that pediatric-inspired therapy have markedly improved the outcome of these patients. In our monocentric study, we analyzed the impact of the allo-SCT on outcome in adults treated within these pediatric-inspired trials. Between April 2002 and March 2010, 75 young adult patients with Ph- ALL were treated in our clinical unit. 70 patients (49 men and 21 women) were in complete remission (CR) (93%) after induction chemotherapy (4 after two courses), 2 died before evaluation (3%) and 3 patients were refractory and died with progressive disease (4%). The median age of the population was 33 years (range, 16–59). Among the 70 patients in CR, 54 (77%) were considered at high-risk ALL and therefore eligible for allo-SCT after 1 or 2 consolidation courses. Baseline high-risk factors were: WBC count of ≥ 30 × 109/L for B-lineage ALL, clinical and/or morphologic CNS involvement, t(4;11) and/or MLL-AF4 fusion transcript, t(1;19) and/or E2A-PBX1 fusion transcript and low hypodiploidy and/or near-triploidy. Fourteen patients with low-risk ALL received chemotherapy alone with late intensification followed by maintenance therapy. With a median follow-up of 36.5 months, median overall survival (OS) for the entire population was not reached and the estimated OS at five years was 75% (70-80%). The high-risk factors as previously defined could separate two different groups with statistically different outcome. In the low-risk (LR) group, none patient died or relapsed during this study. While, in the high-risk (HR) group, 11 of 54 patients (20%) relapsed and 14 patients (26%) died. For the LR group and the HR group, the estimated OS at five years was respectively 100% and 69% (64-74%) (p=0.04) and the estimated disease free survival (DFS) was respectively 100% and 61% (56-66%) (p=0.02). In the HR group, 30 of the 54 patients (55.5%) had donor and had received allogeneic SCT, 28 of 30 patients after myeloablative conditioning regimen, 12 patients with related donor and 18 patients with unrelated donor. The 24 other patients without donor had received the same chemotherapy than patients in the LR group with late intensification and maintenance therapy. There was no difference between the two subgroups for death: 6 patients with donor (D+) and 8 without donor (D-). Nevertheless, there was more relapses in the subgroup D- (8 relapses) than in the subgroup D+ (3 relapses) (p=0.006). At five years, in the subgroup D+, the estimated OS and DFS were respectively 75 % (68-82) and 72 % (66-78). In the subgroup D-, the estimated OS and DFS were respectively 62 % (55-69) and 48 % (41-55). There was no difference between two subgroups D+ and D- for OS (p=0.4) and DFS (p=0.19). In addition, there was no difference for age, sex, risk factor and initial characteristic of the disease. These results suggest that allograft might not improve the outcome of patient with high-risk Ph- ALL. One explanation is that pediatric-inspired induction chemotherapy improves the outcome of the whole population (75% of overall survival) and this advantage decreases the impact of the allo-SCT. Nevertheless, allo-SCT decreased the risk of relapse but did not modify OS and DFS. However, more patients are necessary to confirm these results in a multicentric study. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Recent results from the HELIOS phase 3 study in relapsed/refractory CLL/SLL demonstrated that the addition of ibrutinib to chemoimmunotherapy with bendamustine/rituximab (BR) leads to an 80% reduction in risk of progression or death compared with placebo + BR (Chanan-Khan et al. ASCO 2015). In addition to prolongation of progression-free survival (PFS; median not reached vs 13.3 months; hazard ratio: 0.203, 95% confidence interval: 0.150-0.276, p 1) were stratification factors. Pts with deletion 17p (del17p; 〉 20% of cells) were excluded. All pts were required to have ≥ 1 abnormal lymph node (LN; defined as a measurable lesion 〉 1.5 cm). The primary end point was independent review committee (IRC)-assessed PFS. In this analysis, individual parameters of response (LN, spleen, overall radiology, absolute lymphocyte count [ALC], complete blood count [CBC], and bone marrow [BM]) were evaluated. Minimal residual disease (MRD) was assessed by flow cytometry using an 8-color panel (Rawstron AC, et al. Leukemia. 2007;21:956-964); MRD samples were collected at confirmation of suspected CR (bone marrow) and every 3 months thereafter (peripheral blood). Rate of MRD-negative response was defined as the proportion of pts who reached negative disease status (〈 0.01%, ie, 〈 1 CLL cell/10,000 leukocytes) in any sample. Reported MRD rates are based on the intent-to-treat (ITT) population. Results The ORR assessed by the IRC was 82.7% with ibrutinib + BR vs 67.8% with placebo + BR (p 〈 0.0001), and was consistent with ORR reported by the treating physician (investigator assessed) (ORR: 86.2% vs 68.9%, p 〈 0.0001). However, rates of CR/CRi were higher by investigator assessment (21.4%, ibrutinib + BR vs 5.9%, placebo + BR) than IRC (10.4% vs 2.8%). The IRC employed an independent evaluation of radiological scans including stringent evaluation of LN and volumetric assessment of spleen size-the main reasons for the difference in CR/CRi rates between investigator and IRC assessment. At baseline, similar proportions of pts in each arm had bulky disease defined as LN 〉 5 cm (54%-58%) or abnormal spleen (~40%) as assessed by IRC. Complete resolution of previous CLL/SLL manifestations as assessed by the IRC was achieved more often in the ibrutinib + BR arm in comparison with placebo + BR for LN (34.6% vs 15.2%), spleen (56.7% vs 37.0%), overall radiology (21.1% vs 9.0%), and BM (19.7% vs 5.9%). Rates of normalization of ALC (〉 90%) and CBC (〉 70%) were high and similar in the 2 arms. MRD was assessed in 120 pts treated with ibrutinib + BR and 57 pts treated with placebo + BR and was negative in 37 pts and 14 pts, respectively, which corresponds with an MRD-negative response rate of 12.8% vs 4.8% for ibrutinib + BR vs placebo + BR (p = 0.0011). Investigator-determined responses by different levels of MRD are shown in Table 1. The percentage of pts with an MRD level 〈 1% was higher with ibrutinib + BR vs placebo + BR (32.2% vs 11.8%). Moreover, the percentage of pts with an MRD level 〈 0.1% was higher for ibrutinib + BR vs placebo + BR (24.6% vs 7.6%) suggesting that the depth of response with ibrutinib + BR was superior. Kaplan-Meier plots by MRD level (Figure 1) show that a lower MRD level was associated with a longer PFS. However, pts in the ibrutinib + BR arm had a more sustained response at every MRD level compared with pts in the placebo + BR arm. Conclusions Pts treated with ibrutinib + BR showed not only a higher ORR, but also a greater depth of response, with more CRs and a higher rate of resolution of LN, spleen, and BM involvement. Furthermore, the rate and depth of MRD negativity was improved, and appeared to last longer in pts treated with ibrutinib + BR compared with pts receiving placebo + BR. With a median follow up of 17 months in the ibrutinib + BR arm, no MRD-negative pts and few MRD-positive pts had progressed, thus evaluating a trend in PFS with MRD negativity is currently limited in this arm. Disclosures Cramer: Gilead: Other: Travel grant, Research Funding; Glaxo Smith Klein/Novartis: Research Funding; Astellas: Other: Travel grant; Mundipharma: Other: Travel grant; Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau. Off Label Use: Combination of bendamustine, obinutuzumab and ibrutinib for treatment of CLL. Fraser:Hoffman LaRoche: Consultancy, Honoraria; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Demirkan:Amgen: Consultancy; Celgene: Other: Travel reimbursement. Santucci Silva:Merck: Research Funding; Celgene: Research Funding; GSK: Research Funding; Janssen: Other: Travel reimbursement, Research Funding; Hoffman LaRoche: Other: Travel reimbursement, Research Funding; Novartis: Other: Travel reimbursement. Janssens:Mundipharma: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy. Goy:Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Mayer:Janssen: Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Bartlett:Millenium: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Gilead: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celgene: Research Funding. Rule:Roche: Consultancy, Other: Travel reimbursement; J&J: Consultancy, Other: Travel reimbursement, Research Funding; Celgene: Consultancy, Other: Travel reimbursement; Gilead: Research Funding. Sun:Janssen/J&J: Employment, Equity Ownership. Phelps:Janssen/J&J: Employment, Equity Ownership. Mahler:Janssen: Employment, Other: Travel reimbursement. Salman:Janssen/J&J: Employment, Equity Ownership. Schaffer:Janssen: Employment. Balasubramanian:Pharmacyclics LLC, an AbbVie Company: Equity Ownership; Janssen: Employment, Equity Ownership. Howes:Janssen/J&J: Employment, Equity Ownership. Hallek:AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding.

Description: Abstract 3111 Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare malignancies usually occurring in middle-aged to elderly patients (pts), with an advanced disease and unfavorable international prognostic index (IPI) scores. Excluding ALK-positive anaplastic large cell lymphomas (ALCL) and indolent mycosis fungoides, they are often characterized by a poor prognosis. There is no consensus about optimal therapy and the role of allogeneic stem-cell transplantation (allo-SCT) as first line therapy remains to be investigated. In an effort to explore this therapeutic option in younger pts, we undertook a retrospective analysis in 2 french centers. The records of all pts aged between 18 and 65 years diagnosed with PTCL in Bordeaux and Toulouse between January 2005 and April 2012 were reviewed. Cutaneous T-cell lymphomas and ALK-positive ALCL were excluded. Patients with an IPI score at diagnosis of 0/1 were excluded as well as those who never reached at least a 1st partial response according to the criteria reported by Cheson. Patients relapsing within 3 months after the 1st response and thus ineligible for allo-SCT were also excluded. The primary objective was to compare the outcome of allo-SCT (allo group) as compared to non-allogeneic SCT therapies (no-allo group) in these pts with high-risk PTCL in 1st response. Thirty-three patients were included (16 in the allo group, 17 in the no-allo group). Fifteen pts in the allo group were treated in Bordeaux where allo-SCT was always pursued during the study period in responding pts with an IPI score ≥ 2 at diagnosis. In Bordeaux, the absence of allo-SCT in 1st response was explained by the absence of a suitable donor or the refusal of the patient. The therapeutic strategy in Toulouse was different with 11 pts in the no-allo group, allowing us to undertake this retrospective comparison. In the allo group, conditioning regimes were of reduced intensity (n=12) or myeloablative (n=4). The sources of stem cells were PB (n=13), BM (n=2) or cord blood (n=1). Donors were matched related (n=7), matched unrelated (n=6), mismatched unrelated (n=2). In the whole cohort, the first chemotherapy regimes were CHOP or CHOP-like (n=31), DHAP (n=1), ICE (n=1). In the allo vs no-allo groups, the median ages at diagnosis were 54 years (20–65) vs 59 years (29–64), p = 0.5; the number of pts diagnosed before 2009 were 7 vs 9, p=0.6; the lymphoma subtypes were PTCL-NOS (4 vs 9, p=0.1), angioimmunoblastic (8 vs 6, p=0.4), others (4 vs 2, p=0.3); the IPI scores at diagnosis were 2 (5 vs 5, p=0.9), 3 (6 vs 3, p=0.2), 4/5 (5 vs 9, p=0.2); the number of pts in CR1 and PR1 were 13 vs 13, p = 0,7 and 3 vs 4, p=0.7; the number of chemotherapy lines to reach the 1st response were 1 (8 vs 15, p=0.02), 2 (4 vs 2, p=0.3) or 3 (4 vs 0, p=0.03). Five patients in the no-allo group were treated with an autologous SCT in 1st response. Three patients in the allo group were treated with autologous SCT to reach the 1st response. With a median follow-up of 34 months (8–74) after the 1st response, in the allo vs no-allo groups, the 2-year OS (figure 1) were 87% ± 8% vs 49% ± 13%, respectively (p= 0.06); the 2-year EFS (figure 2) were 81% ± 10% vs 33% ± 12%, respectively (p = 0.007). In the allo and no-allo groups, 3 and 12 pts respectively, have relapsed. In the allo and no-allo groups, 2 and 8 pts respectively, have died, all from disease progression. The modest size of our study and the potential biases inherent to such a restrospective design preclude the declaration of any firm conclusion. However, these preliminary data suggest that patients under 65 years of age with high-risk PTCL (IPI ≥2) might benefit from allo-SCT in 1st response, in comparison with non-allogeneic SCT therapies. Randomized studies are warranted to further delineate the optimal first line therapy in these patients. Our center is currently participating to such an ongoing european study comparing allo-SCT vs auto-SCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1796 Introduction: FCR chemoimmunotherapy is recommended as first line therapy for fit cll patients. Since the 2007 EBMT guidelines based on the previously published trials using FCR, the definition of high risk CLL has evolved, to include biologic parameters (TP53 disruption by deletion/mutation, high b2-microglobulin level, IgVH unmutated, complex karyotype), refractoriness (progression during fluda-based regimen or within 6mo of completion), and also remission duration (high risk if PFS after FCR 5cm 26%, complex karyotype 44% (n=24/54 with karyotype available). According to FCR remission duration, 11.1% of patients were considered as truly FCR-refractory, 47% had PFS

Description: Abstract 4533 The aim of this single center study was to assess the outcome of pts with MM following the first relapse after autologous transplantation, according to whether or not a RICALLO was performed early in 2d response. Records of the patients were reviewed and the criteria for entering the study were: Symptomatic MM treated frontline with a program including single or double ASCT, relapse at any time following ASCT, response (CR, VGPR or PR) to a second line treatment. RICALLO was proposed to pts with no significant co-morbidities, having a suitable donor (either sibling or 10/10 MUD) and who gave their consent after precise information on the risk of the RICALLO. One hundred and seven pts treated between 01/2004 and 02/2011 fulfilling the inclusion criteria were identified. The initial treatment for relapse consisted of VD (37 pts), RD (29 pts), TD (36 pts), VTD (4 pts) or autologous SCT (1 pt). 22 pts received a RICALLO (allo group) while in 2d response, a median 7.7 months (2–36) after relapse. The RIC consisted of fludarabine plus either 2Gy ICT or busulfan and ATG (according to ongoing available protocols in the centre). The graft was PBSC from sibling (N: 8) or MUD (N: 14). 85 pts (CT group) received therapies according to ongoing protocols or available standard of cares. Following further relapses, 11 pts received a RICALLO while in ≥ 3d response in the CT group. The main characteristics of the patients in each group: age, MM prognostic factors at diagnosis, type of 1st line therapy (VAD or bortezomib containing regimens), single or double ASCT, time to relapse after ASCT and 2d line treatment were similar between the 2 groups. The response achieved with 2d line treatment was different between 2 groups (CR + VGPR/other: 8/14 and 7/76 in allo and CT group respectively, p= 0.01) The 3y OS from the time of relapse for the entire cohort was: 47% (CI95%, 41–53). It was of 45% (CI95% 34–56) and of 48% (CI95% 41–55) for the allo group and the CT group respectively (p= ns). The median time from 1st relapse to death was 31 mo in the entire cohort and 20 and 34 mo in the allo group and CT group respectively (p= ns). The causes of death were, relapse in 5 and 33 pts, or treatment toxicity in 8 and 3 pts in the allo group and CT group respectively. Three 3 y EFS (event = 2d relapse or death) was 16% (CI95%, 11–21) for the whole cohort and 16% (CI95%, 6–26) and 19% (CI95%, 13–25) for the allo group and CT group respectively (p= ns). Conclusion: In conclusion, we did not observe any difference in survival or PFS between allo-SCT and CT in patients at first relapse following an auto SCT. Disclosures: No relevant conflicts of interest to declare.