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Introduction: asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor that potently inhibits aberrant kinase activity of the BCR-ABL1 oncoprotein via allosteric binding. asciminib has shown high efficacy profile in heavily pretreated Chronic Myeloid Leukemia (CML) patients with an adequate safety profile in phase I and III clinical trials. However, data from the use of asciminib in real life setting are still scarce.

Sanchez-Guijo: Novartis: Consultancy, Honoraria, Research Funding; Celgene/Bristol-Myers-Squibb,: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Introduction:Anthracyclines plays a key role in the treatment of Diffuse Large B cell Lymphoma (DLBCL). There is a great concern about its cardiotoxicity, especially among elderly patients with raising age and related morbidities. Liposomal doxorubicin (LD) has proven to be efficacious and less cardiotoxic in combinations of neo-adjuvant chemotherapy regimes through phase II and III studies in breast cancer. There are some phase II studies in DLBCL but to our knowledge, controlled randomized studies are pending.

Alegre: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

INTRODUCTION

Introduction: Indolent B cell non-Hodgkin lymphomas are entities without curative treatment nowadays. However, survival has significantly improved since the incorporation of immunomodulatory agents and now immunochemotherapy has become the gold standard. Most treatment strategies use progression free survival (PFS) as a surrogate marker for overall survival (OS), although updated long term results are frequently lacking. Since 1990 our group introduced IFNα-2b to Bagley’s CVP induction regimen, for naïve indolent NHL (LNH-pro study). Herein we report our long term results.

BACKGROUND:Peripheral T/NK–cell lymphomas (PTCL) are a heterogeneous group of neoplasms with a median survival of 2-3 years. Currently, there is not standard treatment although consolidation of response with autologous stem cell transplantation (ASCT) is recommended as front line therapy, except in anaplastic ALK+ and T/NK nasal localized lymphomas.

There is a need to improve the conditioning regimens for allogeneic HSCT, both reducing the regimen related toxicity and improving the anti-leukemic effect. The myeloablative (MA) regimen consisting in intravenous (iv) busulfan (BU) with fludarabine (F) might be a better option than the conventional BU-CY (Cyclophosphamide) combination, since BU and F act synergistically against leukemia cell lines and previous studies with iv BU-F conditioning have reported an improved safety profile over BU-CY.We aimed to evaluate the efficacy and safety of the MA BU-F regimen, delivering iv BU in a one-daily dose after F infusion, since previous pharmacologic and clinical data supported its safety compared with the standard four-daily doses in the HLA identical sibling allogeneic HSCT setting.One hundred thirty seven consecutive adult patients with myeloid malignancies from nine Spanish institutions were recruited from 2005 to 2011. They had a median age of 47 years (range 19–74) and 60% were males. Diagnosis were AML: 80 (58.4%), AML secondary to MDS: 24 (17.5%), MDS: 23 (16.8%) and MPD: 10 (7.3%). At HSCT, the disease stage was 1st CR or untreated in 85 (62%) and more advanced stage in 52 (38%) cases. Patients having Karnofsky < 90% and Sorror CI >1 accounted for 11.7% and 38.3%.The conditioning regimen consisted in F, 40 mg/m2 daily for 4 days (total dose 160 mg/m2) followed by BU, one-daily IV 3.2 mg/kg infusion (total dose 12.8 mg/kg). GVHD prophylaxis consisted in cyclosporine and methotrexate. HSC infusion and post-transplant supportive measures and follow-up were made according each institution policies.Donor graft source was peripheral blood (PB) in 93 (67.9%) and bone marrow (BM) in 44 (32.1%) cases. Median CD34+ cells infused were 4.5 millions/kg (range 0.6–17.8). All but one patient engrafted, with a median of 15 days (range 8–49) to >0.5 ×10E9 PMN/L and 13 days (range 7–149) to >20 ×10E9 platelets/L. The most frequent toxicity was mucositis, which was grade >1, in 68.8% cases. Three patients had hepatic SOS grade >1, and all of them resolved. Median hospitalization time was 30 days (range 17–114). Acute GVHD grade 2–4 incidence was 25% with a median of 32 days (range 12–87) to GVHD onset. The day-100 mortality was 4.8%. The chronic GVHD incidence in 114 patients at risk is 61.4%, with 37.7% of cases in extended form. At the time of this analysis, the median follow-up is 12 months (range 1–74). Crude survival data showed 106 (77.4%) patients remaining alive and 106 (77.4%) relapse free. Overall, 31 patients have died, 19 relapse-related (13.9%) and 12 (8.8%) due to transplant related mortality. Actuarial survival at 12 months is 79.4% and disease free survival is 71.3% in the whole series. Kaplan-Meier analysis showed that advanced age, comorbidities or advanced disease status at HSCT did not predict an inferior outcome.In conclusion, in the HLA identical sibling allogeneic HSCT setting, the BU-F regimen provides an adequate control of myeloid malignancies, with low regimen related toxicity and both reduced day-100 and non-relapse related mortality.Lahuerta: Janssen: Honoraria; Celgene: Honoraria.

Patients with Mantle cell lymphoma (MCL) have an adverse outcome after relapse due to chemorefractory disease with conventional treatments. Bendamustine, a nitrogen mustard compound chemically related to the alkylating agents, has demonstrated high efficacy with a low toxicity profile in reported clinical trials.To analyze the Spanish experience in patients with relapsed/refractory MCL treated with Bendamustine.Retrospective analysis of spanish experience in relapsed/refractory MCL treated with Bendamustine alone or in combination. This study has been approved by local ethical committees.Currently, there are 36 patients registered and 28 are available for this analysis. Patients'characteristics: 69% male, median age 65 years old (range 41–81), 87% ECOG≤ 1, 83% Ann Arbor stage IV, 37% high risk MIPI and 9% blastic variant. Previous regimens were CHOP or CHOP like ± R in 42.5%, HyperCVAD/MtxAraC ± R in 42.5%, R-CVP in 9% and other regimens in 6%. Median number of previous treatments were 2.6 (range 1–6), all patients had received prior Rituximab and 73% had chemosensitive disease to the last treatment. Bendamustine regimen was R-B (R-375mg/m2 D1, B-90 mg/m2 D1-2) in 78% patients, R-B with B-70 mg/m2 in 8%, B alone in 3%, R-B-Bortezomib in 3% and R-B plus consolidation (SCT, Y90Ibritumomab-tiuxetan) in 8%. Median number of cycles was 4.61 (range 1–7). G- CSF support was administered in 43% of cycles. Response: Overall response rate was 73%, with 43% CR & uCR and 30% PR. Survival: Median overall survival from diagnosis is 8,26 years (range: 1.6–11,6 years) without plateau. Median progression free survival (PFS) after Bendamustine treatment was 16 months (95% CI: 11.7–20.4), data that compares favourably with patients' PFS to previous therapy (12 months, 95% CI: 6.5–17.5). Median PFS for patients who achieved CR/uCR is 32.6 months (95% CI: 19.9–45.4) versus 11 months in patients with PR (95% CI: 3.9–18.8). With a median follow-up for surviving patients of 12 months since Bendamustine treatment, the estimated OS at 3 years is 47% (+ SD 14%). Toxicity: No treatment related mortality has been described so far. Over 152 cycles, only 10 hospitalizations due to febrile neutropenia were reported. No one case of lysis tumoral syndrome has been reported.Bendamustine plus Rituximab is a good rescue treatment in non selected pretreated patients with mantle cell lymphoma. CR rate and duration of response seem to reproduce in current clinical practice the good data reported in previous clinical trials and compares favourably with other available treatments.No relevant conflicts of interest to declare.

Disease relapse is the most frequent cause of treatment failure following allogeneic haematopoietic cell transplantation (allo-HCT), and carries a very poor prognosis. A second allo-HCT may be the only curative option for the majority of these patients. Patient and transplant factors that may associate with the outcome of a second allo-HCT are required for clinical-decision making in such high-risk patients.We performed a retrospective analysis of patients receiving a second allo-HCT for disease relapse after a prior allo-HCT reported by GETH centres. Our aim is to analyze our experience in this setting, and to identify factors associated with patient outcome.We present data on 189 patients who underwent a second allo-HCT for disease relapse in Spain up to December 2010 (median year 2004), with a median follow-up for survivors of 54 months (3–224): median age 35 years (range 4–69); 113 male (60%); initial diagnosis AML 77, ALL 45, MDS/MPD 28, CML 23, lymphoprolipherative disorder 12, and others 4. Seventy-five (40%) received myeloablative conditioning. Donors for second allo-HCT were related in 158 cases (84%), and in 33 cases (17%) were new donors different from the donors in the previous allo-HCT. Only 23 cases (12%) had T-cell depletion. Median time from the first to the second allo-HCT was 19 months (1–151). The cumulative incidence of non-relapse mortality was 37%. Median overall survival (OS) was 297 days, with an OS at 1, 3 and 5 years of 39%, 28% and 25%, respectively. Type of donor (related versus unrelated and new donor versus same donor) and type of conditioning (myeloablative versus non-myeloablative) had no association with patient outcome. However, OS was significantly poorer in patients who underwent second allo-HCT in active relapse or progression than in those with low disease burden (complete response, good partial response, or chronic phase; 29% vs 52% at 1 year, 21% vs 39% at 3 years, 17% vs 35% at 3 years, respectively; p=0.001). Also, patients with early relapse after the first allo-HCT who underwent a second allo-HCT <1 year after first HCT also had a poorer OS than those with a later relapse and second allo-HCT (13% vs 53% at 1 year, 7% vs 40% at 3 years, and 5% vs 35% at 5 years, respectively; p<0.001). The impact of these two clinical factors in the outcome remained independent in the multivariate analysis (disease status at second allo-HCT: HR 1.8, 95% CI 1.2–2.6, p=0.002; time to second allo-HCT: HR 3.2, 95% CI 2.2–4.6, p<0.001). Time to second allo-HCT and disease status also have an independent association with the probability of progression free survival in this series (p <0.001 and p =0.001, respectively). In fact, while patients with late relapse who received a second allo-HCT in good response had a very encouraging probability of OS of 49% at 5 years, patients who had an early relapse and required a second allo-HCT in less than 1 year from their first allo-HCT and also had active disease at the time of second allo-HCT had very poor OS of only 8% at 1 year and no one survived beyond 3 years after the second allo-HCT.25% of patients who relapse after an allo-HCT can achieve long-term survival of 5 or more years following a second allo-HCT. Donor type does not appear to influence the outcome. On the contrary, our data suggest that disease status at HCT and time to relapse between first and second HCT are two significant prognostic factors with independent impact on patient outcome. The indication of a second allo-HCT in this context should be thoroughly discussed for individual cases, in particular for patients with early relapse and refractory disease arriving to second allo-HCT, for whom the probability of prolonged survival is extremely low.No relevant conflicts of interest to declare.

Abstract 4942

Abstract 3056

Abstract 3010FN2This icon denotes a clinically relevant abstract

Survival of Follicular Lymphoma patients has significantly increased with the introduction of immunomodulatory agents, such as Interferon (IFN) and Rituximab (R). Until 2002 our Follicular Lymphoma patients were included in a trial and received induction therapy with CVP + Interferon (LNH-pro, JCO 16; 1538–1546). Since 2006, Rituximab is being added to the same induction regimen (LNH-pro-05, EHA 09). Herein we communicate the comparative results between these two trials in Intermediate-High risk Follicular Lymphoma patients.To compare toxicity and efficacy in terms of complete remission (CR) and Progression Free Survival (PFS) between both trials in Intermediate-High risk Follicular Lymphoma patients.Patients in the LNH-pro trial (1990-2006) received CVP (CY 400mg/m2 p.o D1-5, VCR 1.4mg/m2 iv D1, PRD 100mg/m2 po D1-5) + IFN (3MU/m2 sc, 3 times/wk, for 12 wks). When it became available, G-CSF support was permited. In the LNH-pro-05 trial (2006-ongoing), Rituximab (R: 375mg/m2 iv D1) was added to the same induction regimen. All patients received 8 cycles as per protocol, with G-CSF support and Pn. jiroveci prophilaxis. In both studies, complete re-assessment was performed after cycle 4, at the end of induction therapy, every 4 months for the first 2 years and every 6 months thereafter.We analysed data from 74 and 36 FL patients with FLIPI≥2, included in the LNH-pro and LNH-pro-05 trials, respectively. Patients' characteristics are shown in table 1. No significant differences were found between groups, except for a higher incidence of elevated B2-microglobulin in patients treated with CVP+IFN and higher Bulky disease (>7cm) among patients with R+CVP+IFN. Median number number of cycles were 6 and 8, respectively. Response: Seventy one patients (96%) in the LNH-pro Trial (CVP+IFN) were evaluable for response. Overall Response (OR) rate was 87%, with 68% Complete Remission (CR) and 19% Partial Remission (PR) (9% non-responders).In the LNH-pro-05 Trial (R+CVP+IFN), 36 patients (92%) and 33 patients (83%) were evaluable for response after 4th and 8th cycle. At cycle 4, all assesed patients achieved remission (15% PRs and 85% CR+uCR), while after the 8th cycle 100% of patients are in CR or uCR. Toxicity. Main hematologic grade 3–4 toxicity was neutropenia, 33% for CVP+IFN and 28% for R+CVP+IFN, with 12% and 6% of infections, respectively. Other non-hematologic toxicities were infrequent and mild (5% and 10% in each group). Eight percent of patients in the LNH-pro trial withdrew treatment due to toxicity. At the moment, none of the patients in the LNH-pro-05 trial have experienced an unacceptable toxicity. Survival . Median follow-up was 7.7 years for CVP+IFN and 2 years for R+CVP+IFN. A significant increase of PFS was seen among patients who received R (66% vs. 86%, at 3 years, P 0.05). There is also a trend to a longer overall survival in patients treated with R+CVP+IFN (P 0.07).The addition of Rituximab to CVP+IFN induction regimen in Intermediate-High risk Follicular Lympoma patients, significantly increases complete remission rates (88% to 100%) and progression free survival (86%, at 3 years), with a low toxicity profile.No relevant conflicts of interest to declare.

Abstract 2867