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Return to work (RTW) is a marker of functional recovery in cancer patients, with quality of life, financial and social implications. We investigated frequency and factors associated with RTW in a cohort of patients younger than 66 years, with newly diagnosed multiple myeloma (MM), uniformly treated with a bortezomib-based induction followed by autologous stem cell transplantation (ASCT). Socio-economic and working status data were collected by a self-administered questionnaire. One hundred and eighty-six patients entered the study. Of whom, 145 (78%) where employed at diagnosis, which was more frequent in younger (median 55 vs. 60 years, p < 0.001), men (59.3% vs. 34.2%, p = 0.004), and with college studies (44.8% vs. 24.4%, p = 0.008). Forty-three (30%) of the 145 patients who had a job at diagnosis, RTW after ASCT in a median of 5 (range 1-27) months. Factors independently associated with RTW were having three or more children (HR 2.87, 95% CI 1.33-6.18), college studies (HR 2.78, 95% CI 1.21-6.41), and a family income >40 × 10(3)€/year (HR 2.31, 95% CI 1.12-4.78). In conclusion, the frequency of RTW herein reported in MM patients seems lower than reported in other malignancies. The risk factors observed may guide the design RTW programs.

Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not benefitting enough from new anti-MM agents. We retrospectively analyzed the profile of and treatment patterns and outcomes in 675 transplant-ineligible patients with MM who started frontline therapy in routine practice. The mean (SD) age was 75.6 (6.7) years; 152 (47.4%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 2-4, and 73 (25.1%) had high cytogenetic risk. The most frequent frontline therapy was non-VMP bortezomib-based regimens (n=207; 30.7%), which were more frequent among patients with ECOG PS 0/1 and higher risk (e.g., international staging system (ISS) stage III, severely impaired glomerular filtrate rate (GFR), high lactate dehydrogenase (LDH), and high-risk cytogenetics); 185 patients (27.4%) started an attenuated (lite) VMP regimen, and 159 (23.6%) a VMP (VISTA) regimen. Median progression-free survival and overall survival (OS) were 15.3 months (95%CI 14.0-16.9) and 33.5 months (95%CI 29.1-37.2), respectively; 405 patients (78.2%) achieved partial response or better. Age, ECOG PS, ISS stage, serum LDH, GFR, cytogenetic risk, and treatment regimen significantly influenced OS. In this study, a remarkable proportion of transplant-ineligible patients with MM were older, frontline regimens were highly heterogeneous, and patients at higher risk often received less efficacious combinations. These findings suggest that clinicians have limited objective criteria for therapeutic decisions for this patient group.

Introduction: Daratumumab is an anti-CD38 agent that was first investigated as single agent in GEN501 and SIRIUS trials in patients with advanced multiple myeloma (MM). Overall response rate (ORR) was 30% with positive impact on progression-free survival (PFS). However, there is a lack of information regarding plasmacytoma response. Materials and Methods: Here, we described a heavily pretreated group of 43 patients who received daratumumab monotherapy after EMA approval and focused on plasmacytoma response. Results: After a median follow-up of 26 months, median time to best response was 2.9 months (range 0.8-13.1), median PFS was 5.2 months (95% CI 2.5 ??? 8.8) and median OS was 11.2 months (95% CI 6.3 ??? 17.0). Patients who achieved at least partial response had longer median PFS and OS (12.8 and 20.2 months, respectively) than those who achieved minimal response or stable disease (5.3 and 11.2 months, respectively). Ten patients (23%) had plasmacytomas (70% paraskeletal, 30% extramedullary). The clinical benefit for patients with and without plasmacytomas was 20% versus 42%. A dissociation between serological and plasmacytoma response was observed in 40% of the patients. Thus, 50% of the patients with plasmacytomas achieved at least serological minimal response but only 20% had plasmacytoma response. Conclusion: This is the first real-world study of daratumumab monotherapy that focuses on efficacy data regarding soft-tissue plasmacytomas in patients with relapsed/refractory mieloma, showing a limited benefit in this patient population.

Previous studies showed antitumor activity for plitidepsin plus dexamethasone (DXM) in relapsed/refractory multiple myeloma (r/r MM), and in vitro synergism with bortezomib (BTZ) or DXM against MM cells. This phase I trial evaluated plitidepsin (3-h intravenous infusion Day 1 and 15), BTZ (subcutaneous bolus Day 1, 4, 8, and 11), and DXM (orally Day 1, 8, 15, and 22), every 4 weeks in 36 r/r MM patients. Twenty-two patients were treated using a standard dose escalation design (10 at the recommended dose [RD] cohort), and 14 additional patients were treated to expand the RD cohort. No dose-limiting toxicities (DLTs) occurred during dose escalation. The highest dose level evaluated (plitidepsin 5.0 mg/m2 , BTZ 1.3 mg/m2 , DXM 40.0 mg) was the RD for phase II studies. Results shown herein are focused on this RD. Two patients had DLTs (grade 3 diarrhea, and grade 3 nausea/vomiting refractory to antiemetic therapy). Grade ? 3 hematological toxicity (thrombocytopenia 46%, anemia 33%, and neutropenia 17%) was manageable and did not result in treatment discontinuation. Transient and manageable grade 3 ALT increase (26%) was the most common biochemical abnormality. At the RD cohort, overall response rate was 22.2% (95%CI, 6.4%-47.6%), including one stringent complete response, one very good partial response, and two partial responses in r/r patients to BTZ and/or lenalidomide. The clinical benefit rate was 77.8% (95%CI, 52.4-93.6%). No major pharmacokinetic drug-drug interaction was found. In conclusion, the triple combination of plitidepsin, BTZ, and DXM showed an acceptable safety profile and had moderate activity in adult patients with r/r MM. FUNDING: The study was funded by Pharma Mar, S.A. ACKNOWLEDGMENTS: The authors thank the patients, their families, and investigators teams for their participation in this phase I clinical trial.

Introduction Treatment of relapsed/refractory multiple myeloma (RRMM) is highly challenging, especially for patients with disease refractory to initial therapy, and in particular for disease developing refractoriness to lenalidomide. Indeed, with currently approved treatments, median progression-free survival (PFS) in the lenalidomide-refractory setting is less than 10 months, reflecting the difficulty in treating this patient population. Pomalidomide is a second-generation immunomodulatory drug that has shown activity in lenalidomide-refractory disease in the setting of different combinations. Patients and Methods A real-world study was conducted by the Spanish Myeloma group in a cohort of patients with RRMM treated with pomalidomide, cyclophosphamide, and dexamethasone (PomCiDex). One hundred patients were treated with a median of 3 prior lines of therapy. Results Overall response rate was 39%, with a clinical benefit rate of 93%. Median PFS was 7.6 months; median overall survival (OS) was 12.6 months. Median PFS and OS survival were consistent across the different subgroups analyzed. Prolonged PFS and OS were found in patients with responsive disease. Conclusion Our results compared favorably with those obtained with different pomalidomide-based combinations in a similar patient population. PomCiDex remains a manageable, cost-effective, and all-oral triplet combination for RRMM patients.

Multiple myeloma (MM) is a recurrent malignancy with a high impact on quality of life. Improved survival relies on the combination of drugs and extended duration of therapy, raising concerns on its toxicity burden in elderly patients. Health-related quality of life measurements attent to capture health aspects relevant to patients other than efficacy. This prospective study aimed to understand the relationship between MM-related symptomatology and other quality of life dimensions using the EORTC QLQ-MY20 questionnaire in individuals with relapsed or refractory MM. Irrespective of treatment modality, over 50% of patients who responded to treatment had significant omprovements of reported scores in all domains. Conversely, disease progression was associated with score deterioration not only in the MM-related symptoms domain but also in all other domains. HRQoL adds valuable information to the established efficacy endpoints but an adequate interpretation of HRQoL outcomes in randomized trials should require stratification according to response.

This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty‐seven RRMM patients with a median of three prior lines (2–8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1·25 mg/m2 of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1–21 and dexamethasone 40 mg weekly. The defined threshold for success was achieved, with 18 out of 31 patients obtaining at least minor response (MR) in the phase II. In the global population, 51% of patients achieved at least partial response (PR) and 60% ≥MR, resulting in a median progression‐free survival (mPFS) of seven months and overall survival (OS) of 19 months. The main toxicity was haematological. Importantly, patients with low serum levels of alpha 1‐acid glycoprotein (AAG) at baseline (, This trial was funded by Array Biopharma and Celgene Corporation.

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score. B symptoms, and elevated beta 2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and beta 2-micro-globulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001). a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower 05 (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum beta 2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory.

Introduction:Acute myeloid leukemia (AML) real-world incidence has been investigated in a limited number of European countries such as Sweden, Denmark and a few others. These prospective population-based analyses give a more precise idea of AML as a health problem than registry data from cooperative groups or other sources, that usually include selected cases as part of research studies and/or therapy trials. In October 2016, the Autonomous Government of Catalonia funded a project (PERIS SLT002/16/00433) to prospectively collect all AML cases from our territory. Objective:To investigate the incidence, characteristics and treatment decisions in all consecutive AML patients diagnosed in Catalonia between January 2017 and December 2019. Methods:Inclusion criteria were diagnosis of AML according the WHO 2016 criteria, both primary and secondary (APL excluded) with an age >18 years. The project was disseminated to all hospitals from Catalonia regardless of their size, having at least one hematologist. A specific informatics tool was implemented for remote reporting of the cases. All data were anonymized. In parallel, a circuit for centralized bio banking of patients' samples was designed. The database included the main clinical, laboratory data as well as the initial therapeutic approach. Cases included in our CETLAM group cooperative studies were automatically linked to the trial database for collecting detailed information. Statistical analyses were performed with R packages. Results:Assuming an incidence of AML of 4 cases per 100,000 inhabitants (based on previous reported data from others), we expected 912 cases during three years in the 7,6 million population of Catalonia. Our prospective registry included 750 consecutive AML patients, 82% of the expected cases. The remaining 18% could be explained by the exclusion of APL, age below 18 years, or underreporting. Seventy percent of patients (n=527) were diagnosed and treated in the 5 large University Hospitals from Barcelona and the two adjacent cities (Badalona and Hospitalet). Table 1 shows the main characteristics of the patients. Among the 390 patients up to 70 years, 272 (70%) were enrolled in the CETLAM AML-12 protocol that included intensive chemotherapy (ICT) and risk adapted hematopoietic cell transplantation (HCT). Forty-one additional patients (11%) in this age group received other ICT in different clinical trials. A remaining 73 patients (20%) were treated with other intensive or non-intensive approaches outside trials. In the group of 360 patients older than 70 years only a 33% (n= 119) were treated under the risk-adapted CETLAM AML-16 protocol for elderly AML patients. This trial included ICT as in the CETLAM-12 in case of favorable genetic features; this was received by 13 of the 119 patients (11%) enrolled. The remaining patients of CETLAM-16 were treated with low-intensity chemotherapy (oral fludarabine, subcutaneous (SC) cytarabine and G-CSF or azacytidine) and 97 additional elderly patients were included in other clinical trials mostly with targeted and hypomethylating agents (27%). Other active therapies outside trials (usually low-intensity) were administered in 50 additional patients (14%) whereas the remaining 94 patients (26%) only received supportive measures (transfusions, hydroxyurea, antibiotics, palliation, or no treatment), because of one or more of the following: advanced age, poor AML features or severe clinical condition. Overall survival (OS) of the whole series at 2 years was 31±2% (CI: 27-35). Patients younger than 70 years had a 2-year OS of 47±3% (CI: 41-53) compared to 11±3% (CI: 7-17) for those above 70 years (p Conclusions:This prospective study is highly representative of the diagnosis and treatment of AML in Catalonia. The median age at diagnosis was 70 years. Of note, 81% of patients up to 70 years were enrolled in ICT trials. The proportion of patients in trials in the elderly group was lower although still remarkable (60%). In this advanced age group, a 26% of patients were treated with supportive measures only. Despite the high inclusion rate in clinical trials, only one third of newly diagnosed AML patients have the probability to survive at 2 years, with a dismal outcome in those above 70 years. Therefore, the investigation of novel and more effective treatments remains mandatory. This series will be detailed and updated during the meeting. Disclosures Salamero: Pfizer:Consultancy;Jazz Pharmaceuticals:Consultancy, Honoraria;Daichii Sankyo:Honoraria;Novartis:Consultancy, Honoraria;Celgene:Consultancy, Honoraria.Olivera:BAYER:Consultancy;Pfizer:Consultancy, Speakers Bureau;Daiichi Sankyo:Consultancy, Speakers Bureau;Boehringer Ingelheim:Consultancy, Speakers Bureau.Sureda Balari:Celgene:Consultancy, Honoraria;Merck Sharpe and Dohme:Consultancy, Honoraria, Speakers Bureau;Sanofi:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;Gilead/Kite:Consultancy, Honoraria;Janssen:Consultancy, Honoraria;Incyte:Consultancy;Roche:Honoraria;BMS:Speakers Bureau;Celgene/Bristol-Myers Squibb:Consultancy, Honoraria;Takeda:Consultancy, Honoraria, Speakers Bureau.Ribera:Pfizer, Amgen:Research Funding;Pfizer, Amgen, Ariad, Novartis:Consultancy, Speakers Bureau.Sierra:Jazz Pharmaceuticals:Research Funding;Pfizer:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Daiichi Sankyo:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astellas:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead-Kite:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction: Immunotherapy is a promising modality of treatment for neoplastic diseases. The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody blinatumomab can transiently engage any cytotoxic T cells to CD19+ target B cells inducing their serial lysis. Blinatumomab has shown promising activity in B-cell non-Hodgkin’s lymphomas and, especially, in B-cell precursor acute lymphoblastic leukemia (ALL).Areas covered: This review focuses on the chemistry, pharmacological properties, clinical activity as well as the safety and tolerability of blinatumomab used in the treatment of relapsed/refractory (R/R) (including minimal residual disease-positive [MRD+]) ALL in adults and children.Expert opinion: Blinatumomab has demonstrated encouraging response rates in the setting of MRD+ and in R/R ALL in adults and children. Blinatumomab has a favorable safety profile, although reversible CNS events and cytokine release syndrome can occur. Encouraging reports on the activity of blinatumomab in the R/R B-c...

About 25–35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18–60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.

The karyotype is an important predictor of outcome in acute lymphoblastic leukemia (ALL). Rearrangements of the 11q23 region involving the KMT2A gene confer an unfavorable prognosis. Forty-six adult ALL patients from the PETHEMA Group treated with risk-adapted protocols, with t(v;11q23) were selected for this study. Complete response (CR) was attained in 38 patients; 25 remained in CR after consolidation. Twelve (48%) received allogeneic hematopoietic stem cell transplantation (HSCT) and 13 delayed intensification and maintenance. The 5-year CR duration probability was 37% (95% CI, 19%-55%). A trend for a longer CR duration was observed in patients undergoing HSCT vs. those receiving chemotherapy. The 5-year overall survival (OS) probability was 20% (95% CI, 5%-35%). The OS was better, albeit not significant, in patients with a MRD level< 0.1% after induction (39% [95% CI, 14%-64%] vs. 13% [95% CI, 0%-36%]). Specific treatment approaches are required to improve the outcome of patients with KMT2A-rearrangements.

Objective: Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. Methods: Patients with consecutive MM

BACKGROUND The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group. METHODS The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed. RESULTS Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantation CONCLUSIONS Our study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment. Cancer. © 0000 American Cancer Society Cancer 2014;120:3958–3964. © 2014 American Cancer Society.

Background aims The increasing scarcity of young related donors has led to the use of older donors for related allogeneic hematopoietic stem cell transplantation (HSCT). This study analyzed the influence of age on the results of mobilization of peripheral blood stem cells (PBSCs) in healthy donors as well as on the engraftment and outcome of HSCT. Methods A retrospective analysis from a single center was performed comparing the results of PBSC mobilization from related healthy donors according to their age. Results The study included 133 consecutive related donors. The median age was 50 years (range, 4–77 years); 70 (53%) donors were males, and 44 (33%) were >55 years old. All donors were mobilized with granulocyte colony-stimulating factor for 5 days. The peak CD34 + cell count in peripheral blood was higher in younger than in older donors (median, 90.5 CD34 + cells/μL [range, 18–240 CD34 + cells/μL] versus 72 CD34 + cells/μL [range, 20–172.5 CD34 + cells/μL], P = 0.008). The volume processed was lower in younger than in older donors (16,131 mL [range, 4424–36,906 mL] versus 18,653 mL [range, 10,003–26,261 mL], P = 0.002) with similar CD34 + cells collected (579.3 × 10 6 cells [range, 135.14 × 10 6 –1557.24 × 10 6 cells] versus 513.69 × 10 6 cells [range, 149.81 × 10 6 –1290 × 10 6 cells], P = 0.844). There were no differences in time to recovery of neutrophils and platelets or in the incidences of acute and chronic graft-versus-host disease, overall survival, non-relapse mortality and relapse incidence. Conclusions Donors >55 years old mobilized fewer CD34 + cells and required a greater volume to collect a similar number of CD34 + cells. The outcome of HSCT was not influenced by donor age. Donor age should not be a limitation for related allogeneic HSCT.

Lenalidomide plus dexamethasone (Ld) is still considered an option of care for some selected patients with relapsed or refractory multiple myeloma (RRMM) despite the superior efficacy of lenalidomide-based triplet therapy. The aim of this multicenter retrospective study of 227 patients was to characterize those with disease with good response to Ld salvage therapy for RRMM. Obtaining at least a partial response (PR) after the first treatment cycle was the major predictor of a long-lasting response. If Ld is to be considered a treatment choice, at least a PR should be obtained after the first cycle to maintain double-agent therapy safely. Background: Lenalidomide plus dexamethasone (Ld) is still considered an option of care for some selected patients with relapsed or refractory multiple myeloma (RRMM), despite the proven superiority of lenalidomide-based triplet therapy. Up to 20% of patients obtain long-term benefit from Ld alone. The aim of this multicenter retrospective study was to identify and characterize those with good response to Ld salvage therapy, defined as progression-free survival lasting more than 24 months. Patients and Methods: Patients treated with Ld in a consortium of 3 tertiary-care hospitals (Institut Catala d'Oncologia) between 2009 and 2016 were prospectively registered; 227 patients had evaluable data. Results: In multivariate analysis, obtaining partial response after the first therapy cycle was the main independent factor associated with progression-free survival lasting more than 24 months. Together with standard risk cytogenetics, partial response after first cycle was also independently associated with a higher rate of complete response. Previous plasma-cell dyscrasia remained as the only baseline characteristic independently associated with long-lasting responses. High-risk cytogenetics and no history of monoclonal gammopathy of undetermined significance were the only statistically significant negative prognostic factors for overall survival. Patients who had received only one prior therapy showed a trend toward higher overall survival. Conclusion: If Ld is to be considered a treatment choice, at least a partial response should be obtained after the first therapy cycle to maintain double-agent therapy safely.

It is unclear whether higher CD34 + cell doses infused for ASCT have any influence on survival or relapse in patients with lymphoma. We analyzed the correlation of infused CD34 + cell dose with relapse, survival, and hematopoietic recovery in 146 consecutive patients undergoing ASCT for lymphoma. Higher doses (>5 × 106/kg) were significantly correlated with earlier hematopoietic recovery, fewer infectious episodes, lower transfusion needs. No differences were observed in lymphoma outcomes (4-year relapse incidence of 38% [95%CI: 29%–48%] in the lower dose group versus 51% [95%CI: 30%–69%] in the higher dose group, 10-year OS probabilities of 58% [95%CI: 48%–68%] versus 75% [95%CI: 59%–91%], 10-year DFS probabilities of 47% [95%CI: 37%–57%] versus 42% [95%CI: 23%–61%], p = NS for all outcomes). In this series, a higher infused CD34 + cell dose did not correlate with survival or relapse but correlated with earlier hematopoietic recovery and lower resource consumption.

Despite the improvement in prognosis since the advent of rituximab, follicular lymphoma is still incurable and remains the cause of death of most afflicted patients. With the expanding knowledge of the pathogenesis of B-cell malignancies, in the last few years a plethora of new therapies acting through a variety of mechanisms have shown promising results. This review attempts to analyze the evidence available on these new drugs, which include new monoclonal antibodies and immunoconjugates, the anti-angiogenic and immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, inhibitors of B-cell receptor pathway enzymes, such as ibrutinib, idelalisib, duvelisib and entospletinib, BCL2 inhibitors and checkpoint inhibitors. We conclude that despite the high expectations around the new therapeutic options for patients with refractory disease, these new drugs have side effects that require caution with their use, particularly in light of the still short follow up and the lack of both randomized trials and data on combination regimens.

Resumen Fundamento y objetivo El uso creciente de tratamientos antineoplasicos ha provocado un aumento de la incidencia de leucemias agudas secundarias (LAS). El objetivo de este trabajo fue describir las caracteristicas de las LAS en un solo centro. Pacientes y metodo Se registraron 23 casos de LAS. Se analizaron los agentes citotoxicos utilizados, tiempo hasta el diagnostico, caracteristicas clinico-biologicas, tratamiento y pronostico. Resultados La edad mediana fue de 61 anos. Los agentes administrados en la neoplasia previa fueron: alquilantes (17 pacientes), inhibidores de la DNA topoisomerasa II (14), antitubulina (12), radioterapia (9, en 6 con quimioterapia) y antimetabolitos (6). La mediana de tiempo hasta la aparicion de la LAS fue 3 anos (extremos 1,2-15,8). Trece pacientes recibieron quimioterapia intensiva (3 se consolidaron con un trasplante de progenitores hematopoyeticos [TPH]) mientras que los 10 restantes recibieron tratamiento de soporte (mediana de supervivencia de 3 anos frente a 0,079 anos, p = 0,004). Conclusiones En este estudio, la LAS se asocio con la exposicion de agentes alquilantes, inhibidores de la topoisomerasa II y agentes antitubulina. La respuesta al tratamiento y el pronostico fueron malos, aunque la quimioterapia y el TPH podrian proporcionar una supervivencia mas prolongada.

Resumen Fundamento y objetivo La enfermedad del injerto contra el huesped (EICH) aguda grave y la cronica extensa resistentes a glucocorticoides tienen mal pronostico. El infliximab ha demostrado eficacia en algunos pacientes con EICH. Se evaluo la eficacia y la toxicidad del infliximab en pacientes con EICH en un centro. Pacientes y metodo Analisis retrospectivo de la evolucion de 9 pacientes con EICH aguda o cronica resistente a glucocorticoides tratados con infliximab. Resultados Seis pacientes con EICH aguda y 3 con EICH cronica recibieron infliximab semanal como tratamiento de rescate. La fuente de progenitores fue la sangre periferica en 8 y la sangre de cordon umbilical en 1 paciente. Seis recibieron un trasplante de progenitores hematopoyeticos (TPH) alogenico emparentado y 3 un TPH alogenico no emparentado. El numero de dosis de infliximab administradas oscilo entre 2 y 7. Cinco pacientes alcanzaron una respuesta parcial y el resto no fueron evaluables. Todos presentaron complicaciones infecciosas. Conclusiones El infliximab proporciona una respuesta transitoria en el tratamiento de la EICH resistente a glucocorticoides, pero se asocia con una alta tasa de infecciones. La administracion precoz de infliximab podria reducir su frecuencia y gravedad.

Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observation). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p=0.179), and 37% (40/107) of patients in complete response relapsed (RT 42%, COMBINED 27%, CHEMO 41%, p=0.371). Progression-free survival (PFS) and overall survival (OS) probabilities at 10 years were similar in RT, COMBINED and CHEMO patients (PFS 41%, 61% and 39% [p=0.167], and OS 77%, 81% and 72% [p=0.821], respectively), while the COMBINED group showed a trend to better time-to-progression (TTP 43%, 72% and 47% [p=0.055]). On multivariate analysis, only a FLIPI score ≥2 showed a trend to influence PFS (HR 2.1 [95% confidence interval 0.9-4.6], p=0.067), and OS (HR 2.4 [0.9-6.5], p=0.084), while patients treated with radiotherapy plus chemotherapy (COMBINED group) showed a significantly better TTP compared with those receiving only RT (HR 0.3 [0.1-0.8], p=0.024). In our study no benefit was observed in survival with the use of systemic therapy compared with local radiotherapy.

The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group.The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed.Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantationOur study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment.

Background. About 25-35% of adult patients with acute lymphoblastic leukemia (ALL) show the Philadelphia (Ph) chromosome. Their outcome has improved with the combination of tyrosine kinase inhibitors (TKI) and chemotherapy, generally followed by allogeneic hematopoietic stem cell transplantation (alloHSCT). However, few series have evaluated the prognostic value of the additional cytogenetic alterations (ACA) to the Ph chromosome, with contradictory results. The aim of this study was to analyse the frequency, type and prognostic significance of ACA to the Ph chromosome in young adults with Ph+ ALL treated with the ALL Ph-08 trial from the PETHEMA group. Patients and methods.Between 2008 and 2016, 95 patients with Ph+ ALL from 30 Spanish hospitals were included in the ALL Ph08 trial. This trial includes concurrent administration of imatinib (600 mg/d) and standard induction and consolidation chemotherapy, followed by alloHSCT (or autologous HSCT if alloHSCT not feasible) and maintenance chemotherapy with imatinib in cases of MRD persistence of reappearance after alloHSCT (Ribera et al, Br J Haematol 2012; 159: 78-81). The cytogenetic reports were centrally reviewed. Major molecular response (MMR) was defined as BCR-ABL/ABL ratio ²0.1% and complete molecular response (CMR) as BCR-ABL/ABL ratio ²0.01% or undetectable. Results. In 74 out of 95 patients the karyotype was evaluable after review (in the remaining 21 cases the diagnosis was carried out by FISH [n=9] or PCR [n=12]). The median age of the 74 patients was 39 years (limits 19-63) and 44 patients (59%) were males. The median WBC count was 17.6x109/L (limits 0.2-390) and 8 out of 66 evaluable patients had CNS involvement at diagnosis. The CR rate was achieved in 72/74 patients (97%) (1 patient did not achieve CR and 1 died during induction therapy). To date, 57 patients underwent to HSCT, of them 46 were in MMR, at least, at the time of HSCT. With a median follow-up of 1.89 years (limits 0.10-7.38) the probabilities of the CR duration, OS and EFS at 4 years were 69% (95%CI: 54%-84%), 39% (23%-55%) and 38% (23%-53%), respectively. Out of 74 patients, 52 (70%) showed at least one ACA and in the remaining 22 (30%) the t(9;22) was the only cytogenetic alteration. No clinical or biologic differences were observed on comparison of the two groups of patients. Twenty (27%) out of 73 evaluable patients showed trisomies and 19 (26%) monosomies. No differences in CR attainment were observed according the presence and type of ACA. The 4-yr. probability of CR duration in patients with t(9;22) and one or more monosomies (monosomal karyotype) vs. those without monosomies was 23% (95%CI: 0%;49%) vs. 88% (77%;99%) (p Conclusions. In young patients with Ph+ ALL treated within the ALL Ph08 trial, the frequency of ACA was high, being trisomies and monosomies shown in similar frequency. The monosomal karyotype was the most important unfavourable prognostic factor in this series of patients. Funded in part by grants PI10/01417 (FIS), RD12-0036-0029 from RTICC, Instituto Carlos III and RD14-SGR225(GRE), Generalitat de Catalunya. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Background Pomalidomide and dexamethasone (Pom-Dex) represents a standard of care for relapsed and refractory MM patients, with a 30% response rate and a PFS of approximately 4 months (San Miguel Lancet Oncol. 2013). These data have prompted the search for novel combinations with standard and novel agents using Pom-Dex as backbone therapy in order to improve its efficacy. Filanesib (ARRY-520) is a kinesin spindle protein inhibitor, with clinical activity as monotherapy in heavily pretreated MM patients (Lonial ASH 2013). Our group previously demonstrated the preclinical synergy of this therapeutic with Pom-Dex (Hernandez-Garcia ASH 2015), providing the basis for the present trial. Materials and Methods MM patients with disease in progression after at least two prior lines of therapy including bortezomib and lenalidomide, who were refractory or intolerant to lenalidomide and refractory to their last line of therapy were treated until progression with 28-day cycles of filanesib (iv on days 1, 2, 15 & 16), pomalidomide (po days 1-21), and dexamethasone (at a fixed dose of 40 mg po days 1, 8, 15, & 22). Prophylaxis with G-CSF with two 7-day courses starting at day +3 and day +17 was mandatory. A Phase Ib study was initially conducted, that defined the recommended dose of filanesib as 1.25 mg/m2 and pomalidomide as 4 mg QD. Recruitment was continued in the phase II using these doses, and the compiled data of all patients included to date is the focus of the present abstract. Baseline AAG levels were collected in patients included in the Phase II to be correlated with response. Results Thirty-three patients have been enrolled in the trial, 14 in the Phase I (7 of them treated at 1 mg/m2 of filanesib) and 19 patients in the phase II. Median age was 65 years (52-83). The patients had received a median of 3 prior lines of treatment (range: 2-6); 66% were refractory to bortezomib; 94% refractory to lenalidomide, 61% were double refractory to PI and lenalidomide; and 22% had received prior daratumumab. The most frequent treatment-related AEs were hematological: with anemia in 40% of patients (28% G3/4), neutropenia in 76% (60% G3/4), and thrombocytopenia in 56% (28% G3/4). Eighteen patients (76%) had infections, being 10 of them grade 3: febrile neutropenia (n=4), and respiratory infections (n=6). Other non-hematological related AEs were generally low grades, the most frequent-ones being asthenia in 36%, diarrhea in 16% and rash in 12%. A total of 49 SAEs were reported; 24 were considered related to the study drugs. The most frequent ones were G4 neutropenia in 6 cases and infections in 10 cases. Dose reductions were required in 8 patients for filanesib, in 6 patients for pomalidomide and in 1 patient for dexamethasone. Among the 26 patients evaluable for efficacy (7 patients are not evaluable as they are in the 1st two cycles of treatment), 3 (12%) have achieved VGPR and 14 (54%) PR, for an overall response rate (ORR) of 65%; one additional patient (4%) achieved MR and the disease was stabilized in 6 more patients (23%), lasting for at least 3 cycles, for a disease control rate (DCR) of 92%. Median time to first response (MR) was 1 (1-5) months and 3 (1-13) months for 1st PR. After a median follow-up of 7 months, the median PFS was 7 months (CI95 4.2-9.7). Overall survival at 24 months is 75%; five patients have died, one due to influenza A infection (considered non-related) and 4 patients due to progressive disease. Conclusion The results of this ongoing Phase Ib-II trial confirm the preclinical synergy observed with filanesib when combined with pomalidomide and dexamethasone. The combination induces a 65% response rate in this refractory population and a PFS of 7 months. The main toxicity was haematological, particularly neutropenia, which was manageable. Updated results as well as the influence of baseline AAG levels on response will be presented at the meeting. Disclosures Ocio: Array Pharmaceuticals: Research Funding; BMS: Honoraria; Seattle Genetics: Consultancy; Janssen: Honoraria; Mundipharma: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy; Pharmamar: Consultancy; Amgen: Honoraria, Research Funding; MSD: Research Funding. Rodriguez-Otero: Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau. de la Rubia: Amgen: Other: Honoraria; Janssen: Other: Honoraria; Celgene: Other: Honoraria. Oriol: Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: sponsored symposia; Celgene: Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: sponsored symposia, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: sponsored symposia, Speakers Bureau. Lahuerta: Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria. San Miguel: Sanofi: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity9s Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Roche: Membership on an entity9s Board of Directors or advisory committees. Mateos: Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees.

e300 Second Affiliated Hospital, Third Military Medical University, Chongqing, China; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China Introduction: Multiple myeloma (MM), the second most frequent hematologic malignancy, is characterized by hypercalcemia, renal impairment, anemia, and bone lesion. Lenalidomide (Revlimid) is thought to improve treatment outcomes for MM by various mechanisms, such as immune regulation and anti-microangiogenesis. We performed this registry study to evaluate the efficacy and safety of lenalidomide in real-world clinical practice in Chinese patients with MM who have received 1 prior therapy. Patients and Methods: This is a prospective, multi-center, observational study. The inclusion criteria required a diagnosis of MM, 1 prior therapy, and lenalidomide as part of standard care for patients’ treatment. The registry will capture data fromz300 patients being prescribed lenalidomide in specified hospitals, and all patients will be followed in the registry for 1 year after enrollment of the last patient. The study was launched in Nov 2013 and is planned to end in Dec 2016. An interim analysis was scheduled when 100 patients were enrolled. The primary endpoint was progression-free survival (PFS), defined as the time from administration of the first dose of lenalidomide to time of treatment failure, including relapse, refractory disease, death, or censored at last follow-up. Response rate ( partial response [PR]) was assessed using International Myeloma Working Group Uniform Response Criteria. Results: At the interim analysis in Oct 2014, 97 patients were enrolled, with a median follow-up of 5.4 months. The median age of patients was 63 years, with more patients being male (62.9% vs. 37.1%). The median duration of MM since first diagnosis was 12.04 months. 54 patients were evaluable for response, while the remaining 43 patients were not followed long enough. 12 CR + sCR (12.4%), 9 VGPR (9.3%), and 18 PR (18.6%) were observed. The median time to response was 2.8months. 10 disease progression events (10.3%) and 4 deaths (4.1%) were observed. The median PFS was not reached, with a 12-month PFS rate of 61.9% (range, 42.1%76.7%). In total, 46 adverse events were documented, most of which were hematologic toxicities (n 1⁄4 17; 17.5%) and infections (n 1⁄4 17; 17.5%). Grade 3/4 toxicities occurred in 12 patients (11.3%), and 2 patients died. Conclusion: Lenalidomide was effective in previously treated patients with MM in a Chinese population, with acceptable toxicities. Longer follow-up and further accrual of patients are warranted. PO-378 PACE as salvage therapy for relapsed or refractory multiple myeloma I. Isola, M. Granell, J.M. Marti, M. Gironella, A. Garcia-Guinon, J. Lopez-Pardo, A. Muntanola, E. Abella, C. Motllo, L. Escoda, J. Sierra, J. Blade, L. Rosinol, C. Fernandez de Larrea, on behalf of the Catalan Group for Multiple Myeloma and Amyloidosis 15th International Myeloma Workshop, September 23-26, 2015 Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clinic de Barcelona, IDIBAPS, Barcelona; Department of Hematology. Hospital de la Santa Creu i Sant Pau, Barcelona; Department of Hematology. Hospital Mutua de Terrassa, Terrassa; Department of Hematology. Hospital de Vall d’Hebron, Barcelona; Department of Hematology. Hospital Arnau de Vilanova, Lleida; Department of Hematology. Hospital del Mar, Barcelona; Department of Hematology. Hospital Germans Trias i Pujol, Badalona; Department of Hematology. Hospital Joan XXIII, Tarragona Introduction: Treatment of patients with relapsed or refractory multiple myeloma (MM) is challenging. Limited evidence suggests that PACE, a combination chemotherapy regimen, could be useful as a salvage therapy for patients with aggressive disease. The focus of this report was to analyze the efficacy, tolerability and durability of response of PACE regimen in a series of patients with relapsed or refractory MM. Patients and Methods: Medical records of all patients with relapsed or refractory MM who received PACE from January 2010 to January 2015 at seven hospitals in Catalonia were reviewed. Treatment with PACE consisted of a 4-day continuous infusion of cisplatin (10 mg/m2/d), etoposide (40 mg/m2/d), doxorubicin (10 mg/m2/d) and cyclophosphamide (400 mg/m2/d) administered every 4 weeks depending on tolerance and efficacy. Results: Forty patients received PACE, with a median of 19.5 months from diagnosis. Patient characteristics are summarized in Table 1. Patients underwent a median of 2 cycles of PACE (range 16). The overall response (minimal response or better) was 55%: 3 (7%) complete remission (CR), 6 (15%) very good partial response, 11 (28%) partial response (PR) and 2 (5%) minimal response. Of the 20 patients in which extramedullary disease response was evaluated, 6 (30%) achieved CR, 8 (40%) PR and 6 (30%) progressed or had stable disease. Median follow-up for all patients was 8.4 months. For the entire cohort, median progression free survival (PFS) was 4.8 months (95% CI 2.8-6.9) and median overall survival (OS) was 9.5 months (95% CI 4.7-14.4). The 22 patients who responded had a median PFS and OS from PACE of 6.6 months (95% CI 3.7-9.6) and 13 months (95% CI 10.4-15.7), respectively. Six of these patients proceeded to allogeneic and 4 to autologous stem-cell transplantation. Two variables were found to have a significant effect on OS: any autologous stem-cell transplantation prior to PACE vs. none (13.3 vs. 6.9 months, p1⁄40.027) and extramedullary involvement at PACE (7.9 vs. 21.2 months, p1⁄40.016). Grade 4 neutropenia and thrombocytopenia occurred in 33 (83%) and 25 patients (63%). Febrile neutropenia occurred in 13 patients, and two patients died due to treatment toxicity within two months of PACE. Conclusion: Treatment with PACE resulted in an overall response rate of 55%; however the PFS was short. In this group of patients with advanced disease, this therapeutic regimen could help to reduce disease burden prior to transplantation. Table I Characteristics of patients receiving PACE (n[40) Gender (male) 25 (63%) Age at diagnosis, median (range), years 52 (33-72) Age at PACE, median (range), years 54 (35-73) Multiple myeloma subtype

Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient.

Background: Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by a high response to immunochemotherapy (ICT). However, patients refractory to first-line ICT have a worse prognosis. The objective of this study was to determine the prevalence of refractory FL, the factors that predict refractoriness as well as the salvage treatment and outcome. Patients and methods: This is a retrospective analysis including stage II-IV FL patients treated with first-line ICT in 3 Spanish institutions. The cohort was divided into ICT-refractory patients (less than partial response after induction or maintenance/consolidation therapy, as well as relapse or progression within 6 months of the last dose of therapy) and ICT-sensitive. Baseline features, therapy received and outcome were analyzed. Results: 283 patients were included, the median age was 58 years-old (range 28 to 85) and 53% were female. 200/231 (87%) had a good performance status (ECOG < 2), 260/295 (88%) presented with stages III and IV and 163/284 (57%) had bone marrow involvement. High-risk FLIPI score was seen in 108/256 (42%), high serum LDH in 78/263 (28%) and high serum B2-microglobulin in 138/253 (54%). RCHOP was administered to 226 (80%), RCVP to 36 (13%) and rituximab in combination with fludarabine or bendamustine-based therapy to 21 (7%). Seventeen patients received consolidation with radioimmunotherapy and 140 received maintenance with rituximab (n=137) or interferon (n=3). Sixteen patients received complementary radiotherapy. Forty-three (16%) patients were ICT-refractory (37 within 6 months of the completion of induction and 6 during or within 6 months of the completion of maintenance/consolidation therapy). On univariate analysis, high-risk FLIPI (OR 5.4, [95% CI 2.3-12.6]), high-risk FLIPI2 (5.4, [2.4-12.4]), B symptoms (3.2, [1.6-6.6]), ECOG ≥ 2 (4.6, [2-10.9]), involvement of > 4 nodal regions (2.3, [1.02-5.3]), hepatomegaly (7.5, [2.6-21.5]), splenomegaly (2.8, [1.4-5.9]), high B2-microglobulin (4, [1.7-9.5]), high serum LDH (3.9, [1.8-8]) and treatment with RCVP (compared with RCHOP, 2.8, [1.2-6.2]) were correlated with refractoriness. On multivariate analysis, high-risk FLIPI score (4.9, [2.1-11.7]) and treatment with RCVP (3.4, [1.2-9.4]) were the only variables associated with refractoriness. After exclusion of FLIPI, ECOG ≥ 2 (3, [1.1-8.4]) and high serum LDH (4.7, [2-11]) were correlated with refractoriness, in addition to RCVP therapy (4.5, [1.5-13.2]). Ten-year OS probabilities in ICT-sensitive and ICT-refractory patients were 83% (95% CI 76%-90%) and 33% (12%-54%), respectively (p Conclusions: In this series of FL treated with first-line ICT, the prevalence of refractoriness was low and occurred most frequently during or within 6 months of induction rather than maintenance/consolidation therapy. FLIPI score and RCVP treatment (compared to RCHOP) were predictive of refractoriness. The response rate of ICT-refractory FL patients to second-line therapy is low and the prognosis is poor. Supported in part by RD12/0036/0029 del RTICC, Instituto Carlos III. Figure 1. Overall survival in immunochemotherapy (ICT)-sensitive and ICT-refractory patients (p Disclosures Sancho: CELLTRION, Inc.: Research Funding. Sureda:Seattle Genetics Inc.: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.

Severe acute graft versus host disease (GVHD) and extensive chronic GVHD not responding to steroids have poor prognosis. Infliximab has reported to be effective in some of these patients. The efficacy of infliximab for the treatment of patients with steroid-resistant GVHD was evaluated.Retrospective analysis to evaluate the activity and toxicity of infliximab in 9 patients with acute or chronic steroid resistant GVHD.Six patients had acute GVHD and 3 chronic GVHD. The source of progenitors was peripheral blood in all patients except one. Six received matched-related SCT and 3 unrelated SCT. Patients received between 2 and 7 doses of infliximab, and 5 achieved a partial response. All patients presented infections: 4 developed Pseudomonas aeruginosa septicemia and 5 probable or confirmed infection by Aspergillus fumigatus.Infliximab provides transient response in steroid-resistant GVHD. However, it is associated with a high rate of infections. Earlier administration of infliximab should be explored to reduce the frequency of infections.

The growing use of antineoplastic treatments has led to an increase in the incidence of therapy-related leukemias (TRL). The objective was to describe the characteristics of TRL.Twenty-three cases of TRL were registered. Chemotherapeutic agents used for the first tumor, time interval, clinical and biological characteristics, treatment and prognosis of the TRL were analyzed.Median age was 61 years. Cytotoxic agents used in previous neoplasm consisted of alkylating agents (17 patients), inhibitors of DNA topoisomerase II (14), antitubulin agents (12), radiotherapy (9, in 6 with radiotherapy) and antimetabolites (6). Median time from diagnosis of the first neoplasm to TRL was 3 years (range 1.2-15.8). Thirteen patients received intensive chemotherapy [with stem cell transplantation (SCT) in 3] and the other 10 received symptomatic treatment (median survival 3 years versus 0.079 years, P=0.004).In this study, TRL were associated with exposure to alkylating agents, antitubulin agents and topoisomerase II inhibitors. Response to treatment and prognosis were poor, although chemotherapy and SCT may prolong survival.

Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.

Abstract 4785 Background The karyotype is an important predictor of outcome in adults with acute lymphoblastic leukemia (ALL). Some groups have reported the negative prognostic value of complex karyotype (CK, defined as ≥5 unrelated chromosomal abnormalities) in adult ALL (Moorman et al, Blood. 2007:109;3189-97). On the other hand, monosomal karyotype (MK, defined as ≥2 distinct autosomal chromosome monosomies or 1 single monosomy in the presence of structural abnormalities) has been associated with a worse outcome in patients with acute myeloid leukemia. We aimed to assess the prognostic value of cytogenetic abnormalities, especially CK and MK, in adults with ALL treated with protocols of the Spanish PETHEMA Group. Patients and Methods The karyotypes of 783 adult ALL patients from 63 Spanish centers treated according to the protocols of the PETHEMA Group between 1993 and 2011 were reviewed. The several PETHEMA protocols were risk-adapted (standard-risk –SR–, high-risk –HR–) or subtype-oriented (Philadelphia chromosome [Ph+] ALL -with or without imatinib-, and Burkitt's ALL [BL]). The impact of the main cytogenetic abnormalities as well as of the CK and MK on complete remission (CR) rate, CR duration, overall survival (OS) and event-free survival (EFS) was analyzed. Results The median age of the series was 33 years (range 15–82) and 448 patients (57.2%) were male. The karyotypes of 560 out of 783 patients were evaluable after review: normal karyotype 153 patients, t(9;22) 120, t(v;11q23) 30, t(8;14), t(8;22) or t(2;8) 47, high hyperdiploidy (>50 chromosomes) 53, low hyperdiploidy (47–50 chromosomes) 52, hypodiploidy (45–39 chromosomes) 32 and extreme hypodiploidy ( Conclusions Our study confirms that cytogenetics is a very important tool for risk assessment in adult ALL. Patients with t(9;22) and t(v;11q23) had the worst prognosis and the t(1;19) did not have prognostic significance. The introduction of imatinib in patients with t(9:22) ALL significantly improved their outcome. The CK and the MK were not associated with a worse prognosis in patients treated with risk-adapted or subtype-oriented protocols of the PETHEMA group. Disclosures: No relevant conflicts of interest to declare.

Background: Renal failure (RF) is present in about 20% of patients with newly diagnosed multiple myeloma (MM) and is associated with a poor outcome. Bortezomib-based therapy has shown significant activity in patients with RF, including a higher rate of renal recovery when compared with previous regimens. We report the results of a prospective phase II trial for patients with newly diagnosed MM and RF treated with bortezomib and dexamethasone (VD) (RENVEL: www.clinicaltrials.gov NCT 01084837). Aim: The primary end-point was efficacy in terms of response rate and secondary end-points were recovery of RF, PFS and OS. Patients and Methods: Patients with newly diagnosed MM and renal failure from 11 PETHEMA institutions were included. RF was defined as an estimated filtration glomerular rate (eFGR) < 50 ml/min calculated by the MDRD formula. Patients Results: Between April 9, 2010 and September 13, 2012, 60 patients (42 M, 18F, median age 72 years) were enrolled. The M-protein type was IgG in 14 patients, IgA in 22, light-chain only (Bence-Jones) in 22 and IgD in 2. 85% of the patients had ISS 3 and 19% had high-risk cytogenetics. The median baseline eFGR was 17 ml/min and 40 patients had severe RF defined as eFGR Eighteen patients (30%) were initially considered candidates to receive ASCT. The overall response rate after 4 induction cycles was 77% (28% CR, 23% VGPR, 28% PR, 5% MR, 16% refractory disease). Seven patients did not proceed to ASCT because of progressive disease (4), renal impairment with poor PS (2) and lost of follow-up (1). The response rate of the 11 patients who underwent to ASCT was CR in 8 patients (73%), VGPR in 1 (9%), PR in 1 (9%) and early death (sepsis) in 1 (9%). Grade 3 toxicity was only observed in 3 patients. No patient developed grade 3-4 neurological toxicity and only 2 patients had grade 2 peripheral neuropathy. Forty-two patients (70%) were not candidates to receive ASCT. The median number of cycles administered was 7.5. The overall response rate was 71% (29% CR, 29% VGPR, 14% PR, 2% MR, 17% refractory disease, 7% early death, 2% non-evaluable). 15 patients discontinued therapy because of bortezomib-related toxicity and seven were discontinued due to infectious complications. One patient developed grade 3 thrombocytopenia and grade 3 extrahematological toxicity was observed in 4 patients (gastrointestinal, asthenia, Wernicke-Korsakoff and rash one patient each). Peripheral neuropathy was observed in 18 patients (grade 2: 13 patients, grade 3: 5 patients). Renal response was achieved in 66% of the patients (29% CR, 14% PR, 23% MR). The median time to renal respose was 1.6 months (0.8-2.7). Therteen patients out of 17 (76%) could have been discontinued from dyalisis. The renal response rate was similar in the two groups. After a median follow-up of 26.7 months, the median PFS in ASCT and no-ASCT groups was 33.3 and 16.3 months, respectively. The estimated OS at 36 months were 82% and 72%, respectively. In both groups the PFS was not significantly different among patients achieving renal response vs. those not achieving renal response. In no-ASCT group the OS was significantly longer in patients achieving renal response compared with patients not achieving renal response (not reached vs. 35.3 months, p=0.03). Conclusions: VD is a highly effective regimen in patients with newly diagnosed multiple myeloma and severe renal failure, resulting in a high quality tumor responser and a renal response rate of 66% including a 76% of dialysis discontinuation. Disclosures Rosiñol: Janssen: Honoraria; Celgene: Honoraria. Oriol:Celgene Corporation: Consultancy. Mateos:Janssen: Honoraria; Celgene: Honoraria. De La Rubia:Janssen: Honoraria; Celgene: Honoraria. Jiménez:Janssen: Honoraria. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. San Miguel: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; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Blade:Janssen: Honoraria; Celgene: Honoraria.