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This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Objectives: To assess the usefulness of proton MR-spectroscopy (1H-MRS) and diffusion-weighted MRI (DW-MRI) sequences in the follow-up of CLL-patients with chemotherapy treatment. The monitoring of CLL-patients susceptible to chemotherapy treatment is complicated due to the difficulty in assessing the response to treatment. Chemotherapy leads to changes in bone marrow composition and these changes can be evaluated by functional MR-sequences. Methods: 23 patients diagnosed with CLL by our hospital’s Hematology Service underwent a lumbar MR prior and post-chemotherapy applying 1H-MRS and DW-MRI. The concentrations of water and lipids were quantified applying the quantification program LCModel. The Apparent Diffusion Coefficient (ADC) values were calculated with the Functool program (GE). The Wilcoxon sign test was used to compare pre and post treatment results, considering statistically significant P values lower than 0.05. Results: Responder patients decreased the ratio H2O/lipids concentration measured with 1H-MRS and increased the ADC value on DW-MRI in post-treatment studies (P

Background Subcutaneous (SC) versus intravenous (IV) administration is advantageous in terms of patient convenience and hospital efficiency. This study aimed to compare the effect of optimizing the processes involved in SC versus IV administration of rituximab and trastuzumab on hospital capacity and service quality. Methods This cross-sectional resource utilization study interviewed oncologists, hematologists, nurses, and pharmacists from 10 hospitals in Spain to estimate changes in processes associated with conversion from IV to SC rituximab and trastuzumab, based on clinical experience and healthcare use from administrative databases. Results Efficient use of SC formulations increased the monthly capacity for parenteral administration by 3.35% (potentially increasable by 5.75% with maximum possible conversion according to the product label). The weekly capacity for hospital pharmacy treatment preparation increased by 7.13% due to conversion to SC formulation and by 9.33% due to transferring SC preparation to the cancer treatment unit (potentially increasable by 12.16 and 14.10%, respectively). Monthly hospital time decreased by 33% with trastuzumab and 47% with rituximab. In a hypothetical hospital, in which all processes for efficient use of SC rituximab and/or trastuzumab were implemented and all eligible patients received SC formulations, the estimated monthly capacity for preparation and administration increased by 23.1% and estimated hospital times were reduced by 60–66%. Conclusions Conversion of trastuzumab and rituximab to SC administration could improve the efficiency of hospitals and optimize internal resource management processes, potentially increasing care capacity and improving the quality of care by reducing time spent by patients at hospitals.

Background Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. Methods In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. Results Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60–79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17–10.1 vs 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). Conclusions In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.

Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Introduction: The severity of acute clinical outcomes and mortality in hematologic malignancy (HM) patients infected by SARS-CoV-2 was exhaustively documented in the first weeks of the pandemic. A consistent increased mortality compared to non-cancer patients was observed across studies. In this study we aimed to estimate survival in COVID-19 HM patients by type of malignancy, to describe acute and post-acute clinical outcomes, and to compare outcomes in early and later pandemic periods. Methods: In this population-based registry study sponsored by the Madrid Society of Hematology (Asociación Madrileña de Hematología y Hemoterapia), we collected de-identified data on clinical characteristics, treatment and acute and post-acute outcomes in adult patients with hematologic malignancies and confirmed SARS-CoV-2 infection within the Madrid region of Spain. Our case series included all eligible patients admitted to 26 regional health service hospitals and 5 private healthcare centers between February 28, 2020 and February 18, 2021 with a coverage of 98% on a population of 6.6 million inhabitants. The study outcomes were all-cause mortality, severity of disease (WHO), oxygen support, ICU admission, and follow-up symptoms and signs and complications. Survival probabilities were estimated with the actuarial method and reported overall and stratified by type of malignancy and for two study periods (early cohort,-COVID-19 diagnosis from February 28 to 31 May, 2020, and later cohort, up to February 18, 2021). Results: Of the 1408 patients reported to the HEMATO-MADRID COVID-19 registry, 1166 were included in the present analyses; 839 (72%) had a lymphoid malignancy, including 325 (28%) with non-Hodgkin lymphoma, 50 (4%) with Hodgkin lymphoma and 263 (23%) with multiple myeloma; and 327 (28%) had a myeloid malignancy, including 115 (10%) with myelodysplastic syndrome, 92 (8%) with acute myeloid leukemia (AML) and 87 (7%) with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Overall COVID-19 clinical severity was classified as critical in 19% of patients, severe in 36%, moderate in 22%, and mild in 22%; 10% were admitted to an ICU; 8% were on mechanical ventilation and 19% on noninvasive ventilation. Mild disease increased between early and later period from 15% to 38% of patients; severe disease decreased from 42% to 24%, p At follow-up, 22% reported persistent symptoms related to COVID-19 at 2 months, 16% at 4 months and 14% at 6 months. 381 of 1166 (33%) patients died. Overall 30-day survival was 68%; 2 and 3-month overall survival probabilities were 56% and 53%, respectively. Survival was more favorable for patients with myeloproliferative neoplasms (82%, 69% and 65% at 30-days, 2 and 3 months, respectively) than for those with lymphoid malignancies (68%, 56% and 54%) or myelodysplastic syndrome/acute myeloid leukemia (61%, 51%, 46%), p=001. 285 (37%) patients died in the early period vs 96 (24%) in the later, p Conclusions. A population-based registry in Spain provided strong evidence that although COVID-19 severity decreased over year 1 of the pandemic, mortality remained high, and survival was stable over time in the group of patients with hematological malignancy infected by SARS-Coc-2. A relevant proportion of the infected patients (1 in 6) referred persistent symptoms attributable to COVID-19. The improved clinical management of severe COVID-19 in non-cancer patients that followed the dissemination of evidence-based recommendations did not translate in more favorable survival in patients with hematological malignancies. Research is needed to address the specific characteristics and improve the clinical management of this vulnerable population. Disclosures Martinez-Lopez: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau. Jiménez-Yuste: Pfizer: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Honoraria, Research Funding; BioMarin: Consultancy; Sobi: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding. Kwon: Gilead: Honoraria.

Peter Paschka and Hartmut Döhner contributed equally. Background. SARS-CoV-2 infection (COVID-19) has had a great impact worldwide and its mortality has been reported to be higher in patients with haematological malignancies. However, description of its effects and outcomes among recipient of hematopoietic stem cell transplantation (HSCT) is scarce. Objectives. To describe the characteristics, treatment and outcome of COVID-19 in recipients of HSCT reported to the Madrid registry of COVID-19 ("HEMATO-MADRID COVID-19 registry"). Results. Data of 842 patients from 23 hospitals with haematological malignancies and COVID-19 infection were reported in the Madrid registry between March and June 2020. Among those, 87 (10.3%) patients were HSCT recipients: 58 auto-HSCT and 29 allo-HSCT (7 of them from matched related donor (MRD), 12 matched unrelated donor (MUD) and 10 haplo-HSCT). Characteristics of the population are described in Table 1. Median age at COVID-19 infection was 61 years (IQR, 53-67) and 35 patients (40%) were female. Recipients of auto-HSCT with COVID-19 were older and showed a trend towards a higher incidence of arterial hypertension (28% vs 10%, p=0.067) without statistical differences in other comorbidities; active disease requiring treatment at COVID-19 diagnosis was more frequent in auto-HSCT recipients (65% vs. 21%, p Conclusion. In our multicentric experience in a high COVID-19 impacted area, the median time of COVID-19 infection presentation was relatively late in transplanted patients, however shorter in allo-transplanted patients. COVID-19 related mortality was high in HSCT recipients, significantly higher in allo-transplanted patients. Factors associated to this higher mortality should be further investigated to promptly identify high-risk patients since the pandemic is still highly active worldwide. Disclosures Kwon: Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria. Duarte:Incyte Corporation: Other: Has received speaker and advisor fees. Hernandez-Rivas:Rovi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees. Jimenez Yuste:NovoNordisk: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Grifols: Honoraria, Research Funding; Bayer: Honoraria; Sobi: Consultancy, Honoraria, Research Funding; CSL: Honoraria; Octapharma: Honoraria.

Resumen —La piodermia gangrenosa es un proceso ulcerativo asociado frecuentemente a enfermedades linfoproliferativas. La asociacion a leucemia linfocitica cronica es un hecho excepcional. Describimos el caso de un varon de 72 anos que presento ulceras cutaneas en piernas de 4 meses de evolucion y que posteriormente fue diagnosticado de leucemia linfocitica cronica. El paciente presento curacion total de las lesiones cutaneas tras tratamiento con ciclosporina.

Fundamento La realizacion precoz del trasplante de celulas progenitoras hematopoyeticas (TPH)en pacientes con linfomas no hodgkinianos (LNH) agresivos es una indicacion controvertida. Metodos Analisis retrospectivo de 86 pacientes con LNH agresivos tratados con quimioterapiaMACOP/VACOP-B. El TPH se utilizo como tratamiento de rescate en pacientes con edad inferioro igual a 65 anos con progresion o recaida quimiosensible. Se determinaron las supervivenciaslibre de progresion (SLP) y global (SG) con el metodo de Kaplan-Meier. Se compararon losporcentajes de respuesta y las funciones de supervivencia entre los grupos del Indice PronosticoInternacional (IPI) mediante las pruebas χ2 y log-rank, respectivamente Resultados La mediana de edad de los pacientes fue de 48 anos. El 22% tenian LNH-T y el57% tenian IPI de intermedio-alto y alto riesgo. Hubo 6 muertes por toxicidad (7%), y 42(48,8%) pacientes fracasaron al tratamiento de primera linea. De ellos, 31 fueron candidatos aTPH por edad inferior o igual a 65 anos, aunque finalmente se trasplantaron 21 (incluyendo13 de mayor riesgo). Se observo una asociacion estadisticamente significativa entre la SLP y elIPI: 61,9% para los grupos bajo y bajo-intermedio (menor riesgo) frente al 28,2% para los demayor riesgo (p = 0,0007). Con una mediana de seguimiento de 4,8 anos, la SG fue del80,5% para los grupos de menor riesgo frente al 52,6% (p = 0,01) para los de mayor riesgo, ydel 83,7% frente al 62,0% (p = 0,02) para los mismos grupos en pacientes con edad inferior oigual a 65 anos. La mediana de seguimiento posfracaso del tratamiento quimioterapico fue de42,7 meses. Conclusiones En este analisis retrospectivo la SG de los pacientes con LNH agresivos utilizandoel TPH como tratamiento de rescate es similar a la comunicada utilizando el TPH mas precozmente.

Between January 1989 and November 1995, 259 patients with multiple myeloma (MM), 22 stage I, 57 stage II and 180 stage III at diagnosis were treated with myeloablative high-dose therapy followed by autologous peripheral blood stem cell (PBSC) transplantation. The median time from diagnosis to transplantation was 17 months (6-112). At the time of transplant, 56 patients were in CR, 153 in PR, 25 were nonresponders and 25 had progressive disease. Mobilization of stem cells was performed with G-CSF alone in 141 cases, chemotherapy plus G-CSF in 65, chemotherapy plus GM-CSF in 36 and chemotherapy alone in 17 patients. The conditioning regimen consisted of high-dose melphalan alone in 96 patients, melphalan plus TBI in 73, busulfan plus melphalan in 56, busulfan plus cyclophosphamide in 27 and cyclophosphamide plus TBI in seven. The median durations of neutropenia (>0.5 x 10(9)/l) and thrombocytopenia (>20 x 10(9)/l) were 12 (5-118) and 13 days (5-360), respectively. Transplant-related mortality occurred in 11 patients (4%). Once a stable graft was achieved, 114 patients (44%) received maintenance treatment with recombinant alpha interferon (IFN-alpha). Among the 248 patients evaluable for response 125 (51%) had a CR and 100 had a PR (40%). The median duration of progression-free survival (PFS) and overall survival (OS) after transplantation was 23 and 35 months, respectively. Univariate analysis showed that response status pretransplant, only one line of primary induction treatment and IFN-alpha maintenance treatment post-transplant significantly influenced OS. Female sex, pretransplant responsive disease, and treatment with IFN-alpha post-transplant were the factors significantly influencing PFS. The conditioning regimen and method of stem cell mobilization had no significant impact on OS and PFS. On multivariate analysis the only independent factors associated with a longer survival were the number of chemotherapy courses prior to autologous PBSC transplantation and the pretransplant response status. The present analysis from the Spanish Registry confirms the feasibility of autologous PBSC transplantation in myeloma patients with a very low toxicity (4% toxic deaths). The high complete response rate after transplantation is encouraging. The best results are obtained when the procedure is performed early after the first line of induction therapy and in patients with chemosensitive disease. Whether early high-dose therapy followed by autotransplantation in responding patients is superior to conventional chemotherapy is currently being investigated in prospective randomized studies.

Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849).

Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached >= 10 CD34+ cells per mu L with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected >= 2 x 10(6), average 3.0 +/- 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1 +/- 1.2 (1.9-7.7) x 10(6) CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 +/- 0.8; 8-30) and platelets (day 15; 18.5 +/- 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate. Bone Marrow Transplantation (2011) 46, 52-58; doi:10.1038/bmt.2010.54; published online 22 March 2010

Introduction: In recent years, the multiple myeloma (MM) treatment (Tx) landscape has evolved considerably, with the approval of effective novel agents, such as immunomodulatory drugs (thalidomide, lenalidomide, and most recently, pomalidomide) and proteasome inhibitors (bortezomib and carfilzomib; Chng et al, Leukemia, 2014). However, most patients relapse and patterns of relapse in MM can be heterogeneous (Alegre et al, Haematologica, 2002). Tx rescue for MM relapse should begin at symptomatic clinical relapse (clinR) and probably earlier at asymptomatic biological relapse (BR; specifically when significant paraprotein relapse), according to the International Myeloma Workshop Consensus Panel (Rajkumar et al, Blood, 2011). In the case of asymptomatic BR/progression, rescue Tx could be delayed in a subset of pts (Fernández de Larrea et al, Bone Marrow Transplant, 2014), particularly when M-component and hemoglobin levels are stable. Progressive increases of M-spike blood and/or urine could lead to rescue Tx, even in the absence of clinical symptoms, to avoid complications (ie, renal failure, plasmacytomas, bone lesions; Castelli et al, Clin Med Insights Oncol, 2013). This Spanish registry (EPA-MMBR) is an observational prospective study to describe MM relapse patterns, comparing the impact of Tx decisions (starting Tx at BR vs delaying Tx until clinR). We present the updated preliminary results of this study. Methods: MM pts in (or prior to) first or second BR who had achieved ≥ PR since their last Tx were included. Bi-monthly evaluations were performed. Forty-one Spanish sites are participating after approval from their independent ethics committees, with 410 pts expected to be included. The main objective was to assess time to progression (TTP) from BR in both groups (pts who started Tx at the onset of asymptomatic BR vs pts who started Tx at clinR). Secondary objectives included demographic, clinical, and Tx characteristics; median time from BR to clinR; and response rates. Here we present the results of 138 pts with baseline data (48.4%) of a total of 285 registered. Results: In the cohort evaluated (n = 138), mean age was 67.9 years, and 50.7% were male. MM types were IgG Κ (43.5%), IgG λ (22.1%), IgA Κ (16%), and IgA λ (7.6%). Prognostic stage at diagnosis according to the International Staging System (ISS) was II (32.6%) followed by I and III (22.7% each) and data not available (22%). Pts' cytogenetic risk included standard risk (20.8%), high risk (8.5%), and no cytogenetic alterations (32.3%). More than half of pts (51.5%) had received autologous stem cell transplant, 13.2% consolidation and 21.1% maintenance. After first-line Tx, pts had achieved sCR (16.0%), CR (33.6%), VGPR (28.8%), or PR (21.6%). Pts with BR had a median time from diagnosis to BR of 2.66 years. Tx was delayed until clinR in 51.2% of pts, and 48.8% had started Tx at BR (73.3% of whom had significant paraprotein relapse; Figure); there were no relevant differences in demographic and clinical characteristics between the 2 groups. Median time to BR was 31.97 months. Median time from BR to clinR was 105.0 days. Among pts who started Tx at BR, most pts received lenalidomide-based Tx (75% at first relapse and 70.6% at second relapse). At the time of the analysis, only 3 pts had disease progression (1 in each group). In pts who started Tx at BR, first-line Tx after diagnosis was mainly bortezomib-based (73.3%). sCR was achieved in 20.0% of pts, CR in 33.3%, PR in 26.7%, and VGPR in 20.0%. Since the beginning of the study, Tx was prescribed in 54 pts (39.1%). Since only 3 pts had progressed, further follow-up data, particularly in terms of TTP and survival, are needed to identify differences between these 2 strategies. Conclusions: To our knowledge, this is the first prospective study in MM that evaluates the effects of starting Tx at BR vs starting Tx at clinR. In this updated cohort, we find that almost half of pts started Tx at BR (48.8%). We also found that a higher percentage of pts started Tx at BR with significant paraprotein relapse (73.3%), which seems to be a clear factor guiding Tx decision for the physician. Further follow-up and a complete study are needed to identify the differences between these 2 strategies and to define patients who could benefit from early Tx. Figure 1. Percentage of pts who started Tx at clinR, BR, or significant paraprotein relapse (n = 138). Figure 1. Percentage of pts who started Tx at clinR, BR, or significant paraprotein relapse (n = 138). Disclosures Gironella: Celgene Corporation: Consultancy, Honoraria. Fernández de Larrea:Celgene Corporation: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Lahuerta:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cabañas:Amgen: Membership on an entity's Board of Directors or advisory committees. Lostaunau:Celgene SLU: Employment. Vilanova:Celgene SLU: Employment. 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.

e308 before transplantation for relapsed and/or refractory MM. Material and Methods: The study cohort included 12 patients with heavily treated who had relapsed disease and underwent reduced intensity conditioning (RIC) allo-HSCT from matched related or unrelated donor between 2000 and 2015. The RIC regimen consisted of fludarabine 90-120 mg/m2 and melphalan 100-140 mg/m2. All patients receiving unrelated donor progenitor cells also received antithymocyte globulin as part of their preparative regimen. Results: Themedian patient age was 54 years (range, 29-61 years), and median time fromdiagnosis to transplantationwas 26.0months (range, 19.3-51.1months).Nine patients (75%)hadundergone previous autoHSCT. The median number of previous regimens was 3 (range, 2-5). At the timeof transplantation, 83%of the patientswere in at least partial remission (CR 8%, VGPR 16%, PR 61%). The median time from diagnosis to allo-HSCTwas 26months (range, 19.3-51.1months), and median follow-up in surviving patients after allo-HSCT was 12.3 months (range, 1.9-23.6 months). Progression-free survival (PFS) and overall survival (OS) at one year were 81% and 61%, respectively. On univariate analyses, boretezomib treatmentbefore allo-HSCTpredicted longer PFS (P1⁄40.010). The incidences of acute and chronic graftversus-host diseasewere 17%and42%, respectively.Conclusion: AlloHSCT with RIC is associated with acceptable toxicity and durable remission and survival in relapsed MM. The use of bortozomib as pretreatment before allo-HSCT may offer more benefit.

Autologous peripheral blood stem cell (PBSC) transplantation is widely used to treat patients with multiple myeloma (MM). However, only a small fraction of patients remain free of disease in the long-term and most patients will finally relapse. The clinical presentation of relapse after transplantation is very heterogeneous and few reports have analyzed this situation. We report the clinical patterns of relapses after autologous transplantation of 280 patients with MM included in a Spanish Multicenter Registry.The medical records of 560 patients with MM transplanted in different centers in Spain, included in the Spanish Registry of Transplant in Multiple Myeloma, were reviewed. At diagnosis, 48 (8%) had stage I disease, 143 (25%) stage II and 369 (65%) stage III. The median time from diagnosis to transplantation was 13 months (4-143). The median age was 53 years (23-70). Of the 502 patients assessable for response to intensification therapy after transplantation, 241 (48%) achieved a complete response and 220 (43%) a partial response. The clinical characteristics of 280 patients (52%) who had relapsed after transplantation were retrospectively assessed during long-term post-transplantation follow-up.At a median follow-up of 23 months, 280(52%) patients had relapsed or progressed after transplantation. The median overall survival was 52 months (SE 8), (CI 95% 37-68) and median estimated progression-free survival was 33 months (SE 2.2, CI 95% 27-38). The median period for relapse was 30 months (2-84) with an actuarial risk of progression or relapse at 60 months after transplantation of 78%. The clinical patterns of relapse were very heterogeneous: 40 cases (14%) presented extramedullary manifestations with multiple plasmacytomas as the main symptoms of relapse, with a minimum or null monoclonal component (MC). In 51 cases (18%) only an insidious increase of MC protein in serum or urine was detected without other clinical manifestations. In 6 cases (2%) the relapse had criteria of plasmacytic leukemia. The remaining patients presented progressive increase of MC associated with plasmacytic bone marrow infiltration and different clinical myeloma symptoms, mainly new osteolytic lesions. The therapeutic approach was also very heterogeneous, with a global antitumoral response of 30%. Median overall survival after relapse was 14 months (SE 1.4) (CI 95% 11-17).The patterns of relapse of MM after high-dose therapy are very heterogeneous. The different clinical expressions of relapse may be due to clonal selection after high-dose therapy and could indicate the persistence of a resistant clone. Some patients relapse with extraosseous plasmacytomas without systemic disease. These findings suggest the need for an individualized approach during clinical follow-up after transplantation. Regarding treatment response, patients with myeloma who relapse after high-dose chemotherapy have been classically considered to have few therapeutic options. However, we observed that after different lines of treatment, at least one-third of patients responded, with a median overall survival, after relapse of 14 months. New drugs, such as thalidomide, have been recently proved to be effective in MM patients and could increase the response rate and survival of these patients.

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.

Introduction Indolent lymphomas represent 40% of all subtypes of non-Hodking's lymphoma, of which follicular lymphoma (FL) is the most frequent. Bendamustine is a dual alkylating agent with demonstrated high efficacy and low toxicity profile in reported clinical trials. We present the preliminary results from the experience of Spanish compassionate use registry of this agent as first-line treatment for indolent lymphoma. Methods Retrospective multicenter analysis of patients with indolent non-Hodgkin lymphomas (iNHL) treated as frontline with Bendamustine plus Rituximab (BR) in compassionate use. Clinical efficacy was evaluated according to Cheson criteria (2007) and toxicity according to CTCAE v3.0 scale. This study has been approved by local ethical committees. Results Patients’ characteristics: There are 96 patients registered (9 centers), with the following diagnoses: FL: 62 (64.5%), marginal zone 24 (25%), Waldenström macroglobulinemia 7 (7.3%) and mantle NHL 3 (3.1%). The main clinical features of the series are: 45% males, median age 64 years (range 36-84), 87.1% ECOG≤ 1, 63% Ann Arbor stage IV, 50.5% high risk FLIPI and 43.7% CIRS ≥ 4. Extranodal involvement was present in 79.1% of the patients, bone marrow involvement in 52% and 11 patients (11.9%) had bulky disease. Treatment consisted in 6 cycles of BR (B-90 mg/m2 D1-2, R-375mg/m2 D1) in 95% patients. Median number of cycles administrated was 6 (range 1-8). G-CSF support was administered in 16.1% of cycles. Response and Safety: Overall response rate was 95%, with 65.5 % CR, 13.1% uCR and 16.4% PR in the 61 evaluable patients. Progression was documented in 4.9% of patients. Three exitus ocurred due to aspergillosis, progression and other not related with LNH. Median follow-up period was 14 months (3-47). In general, treatment was well tolerated; over 461 cycles registered, the most common adverse event was hematological toxicity with grade 3-4 neutropenia in 10.4%, grade 3-4 leucocitopenia in 6.9% and grade 3-4 anemia in 1.9% of the cycles. Other toxicities included all grades infections in 3.2% of patients, gastrointestinal in 3.4%, asthenia in 3.2%, chills in 1.1%, and mucositis 0.4%. Only 9 hospitalizations due to febrile neutropenia were reported. Conclusion Bendamustine plus rituximab was an effective and well tolerated regimen for newly diagnosed patients with indolent NHL. Disclosures: No relevant conflicts of interest to declare.

Abstract 3045 Background: Lenalidomide is an oral IMiD® immunomodulatory compound with a dual mechanism of action, namely tumoricidal and immunomodulatory activity, and established clinical efficacy and safety in patients with multiple myeloma (MM). Lenalidomide plus dexamethasone (Len + Dex) was well tolerated and demonstrated significant improvements in response and favorable overall survival (OS) compared with Placebo + Dex in 2 pivotal phase 3 registration trials in patients with relapsed/refractory MM (RRMM; Weber et al, NEJM 2007; Dimopoulos et al, NEJM 2007). Previously, in a phase 3, multicenter, single-arm, open-label, expanded-access study (MM-018), Len + Dex demonstrated a predictable safety profile that can preserve patient quality of life (QoL) (Yong et al Haematologica 2010 [abstract #0944]). Here we report efficacy, safety, and QoL data for patients enrolled in the Spanish cohort of MM-018. Methods: Patients with progressive disease after > 2 cycles of antimyeloma treatment, or after relapse from treatment, with ECOG performance status ≤ 2 received 28-day cycles of Len (25 mg/day, D 1–21) plus Dex (40 mg/day, D 1–4, 9–12, and 17–20 for cycles 1–4; D 1–4 in subsequent cycles). Endpoints included overall response (≥ partial response [PR] by European Group for Blood and Marrow Transplantation criteria) and QoL assessments measured by EORTC QLQ C-30 and EORTC QLQ MY-20 questionnaires at baseline and week 24. All prophylaxis was administered at the investigator's discretion. Results: Sixty-three patients receiving ≥ 1 dose of Len + Dex were evaluated for efficacy, safety, and QoL. Median age was 62 years (21 [33.3%] were > 65 years). Prior therapies included thalidomide (n = 15, 24%) and bortezomib (n = 37, 59%). Additionally, 5 (8%) patients had a history of deep vein thrombosis (DVT), and 23 (37%) had a history of peripheral neuropathy. A PR or better was observed in 49 (78%) patients, including complete response (CR) in 13 (21%), very good partial response (VGPR) in 13 (21%), and PR in 23 (37%) patients. Median time to first response and best response was 2.7 and 4.5 months, respectively. Median duration of response was 18.4 months. Response depth improved after long-term treatment with Len + Dex, and 32/63 (51%) patients received >12 cycles of therapy. Beyond 12 cycles of therapy, 8 patients achieved VGPR and 12 patients achieved CR; compared with 5 patients and 1 patient, respectively, prior to 12 cycles. Median time to progression and progression-free survival were both 13.3 months; median OS has not yet been reached. Forty-two (67%) patients remained on study at 6 months. Compliance to QoL assessment questionnaires was ≥ 80%. Patient-reported improvements in QoL and disease symptoms measured by both questionnaires were observed in nearly all scales. EORTC QLQ C-30 scores revealed clinically meaningful improvement (> 5 points) for global QoL (n = 15, 40%), fatigue (n = 16, 42%), emotional function (n = 15, 40%), physical function (n = 12, 32%), role function (n = 11, 29%), social function (n = 11, 29%), cognitive function (n = 10, 26%), and pain (n = 9, 24%) at 6 cycles compared with baseline. Preservation of QoL in role function, emotional function, social function, and pain scores was observed at 6 cycles when compared with baseline in responders (≥ PR). EORTC QLQ MY-20 results revealed no relevant median change (> 5 points) from baseline in all scales for all patients completing questionnaires at baseline and 6 cycles, except for a meaningful improvement in future perspective scores (median 11.1-point change). Adverse events observed in this study were consistent with those previously reported with Len + Dex. Grade 3/4 hematologic events were experienced by 40 (64%) patients, and included neutropenia (n = 32, 51%), thrombocytopenia (n = 11, 17%), anemia (n = 10, 18%), and febrile neutropenia (n = 4, 6%). DVT (all grades) was experienced by 5 (8%) patients, and only one grade 3/4 new-onset peripheral neuropathy was observed after 6 cycles of treatment. Conclusions: Len + Dex treatment in this expanded-access study demonstrated efficacy and predictable safety, consistent with that of previously published trials for patients with RRMM. More patients achieved VGPR and CR after long-term therapy compared with those receiving < 12 cycles of therapy. Furthermore, QoL assessments at baseline and 6 months revealed that patients treated with Len + Dex showed meaningful improvements in certain QoL and symptom scores. Disclosures: Oriol-Rocafiguera: Celgene: Consultancy; Janssen-Cilag: Consultancy; Novartis: Consultancy. García-Laraña:Celgene: Consultancy; Janssen-Cilag: Consultancy. Mateos:Celgene: Honoraria. Cibeira:Celgene: Honoraria for Lectures; Janssen-Cilag: Honoraria for Lectures; Pharmion: Honoraria for Lectures. Knight:Celgene: Employment. Rosettani:Celgene Corporation: Employment.

Plasmacytic ascites is an infrequent complication of multiple myeloma. To date, only few cases have been reported with a very rapidly fatal course unresponsive to therapy. We describe a patient with plasmacytic ascites and quiescent multiple myeloma of 8 years of duration. Disease progression became apparent due to myelomatous ascites, unexplained fever, pancytopenia and bone marrow infiltration. This case showed a complete and long-lasting response after VAD chemotherapy followed by autologous PBSC transplantation. Ascites in association with MM may respond for lengthy periods to high-dose chemotherapy and ASCT.

Introduction: Justification and Objectives There are little epidemiologic data about Myeloma Multiple in Spain. The heterogeneity and complexity of this pathology, and the several sociodemographic factors, justify the interest of this type of studies. On the other hand, this disease needs a high assignement of welfare and therapeutic resources, and besides new strategies have arisen for its treatment. The Spanish Leukaemia and Lymphoma Foundation (FLL)has analyzed the actual situation of Myeloma Multiple in Spain, compiling several epidemiologic and welfare parameters about the disease in a Multiple Myeloma “White Book” for Spain. Patients and Methods The period of analysis was 10 years, from 1.991 to 2.001. The information was compiled from a Hospital Based Survey about MM and the following official sources: International Agency for Research on Cancer (IARC): “Cancer incidence in Five continents” and “Incidence and Mortaliity for Cancer In Spain, Patterns and Tendences” Data Base of EUCAN and GLOBOCAN (Cancer Incidence, Mortality and Prevalence Worldwide) EUROCARE III study, (IARC Cancer Base Number 5, Lyon, IARCPress). “Natural Changes of Population and Demography. Spanish National Statistic Institute (INE) and National Spanish Center for Epidemiology (CNE.) Official Records for Mortality Rates by MM in Spain in Spanish Regions (CCAA) (death records Demograhy Records of INE). INE Hospital Case Rate Inquest. CMBD Data Base of Department of Health (Inmunoproliferative Neoplasm and Multiple Myeloma, CIE-9 Diagnosis Code: 203.0)The indicators used were: Deaths number, median of age, proportional mortality, mortality rates, mortality rates adjusted by age, gender and potential years of life lost due to multiple myeloma, (item 203 of ICD-10, OMS) during the last ten years in Spain. Results The incidence rates of MM, adjusted to the European population were: 3,54 cases by 100.000/year for men and 2,54 cases by 100.000/year for women. The global incidence rate were 4,44 cases by 100.000/year for men and 4,22 cases by 100.000/year for women. These rates were similar in all geographic regions. Performed predictions show a prevalence increase during the following five years, which means more than 2.400 cases in men and more than 2.100 in women MM cases per year. Regarding mortality, rates, myeloma is a very slightly frequent cause of death: 3.23 cases by 100.000/years of men and 2.3 cases of women. A whole an increase of mortality of 45.2 per cent was observed for the period of time between 1992 and 2001. Comments and Conclusions The MM incidence and mortality rates in Spain for this period were lower than expected in comparison with other European epidemiology studies. Nevertheless we observed that the MM mortality and prevalence rates present a continuous and uniform increment in the last years. Part of these increases can be due to the incorporation of new technologies, more sensitive for diagnosis, and to the increase of aging of the population. Furthermore certain occupational and chemical exposures and other environmental changes could explain these trends.

Rituximab in combination with CHOP-like chemotherapy has demonstrated to improve the results in young and elderly patients with DLBCL compared to chemotherapy alone. Re-treatment with rituximab is feasible in patients with indolent lymphoma, but there is few data on the effect of rituximab in combination with chemotherapy in the re-treatment of relapsed patients with DLBCL who have respond previously to rituximab + chemotherapy. In order to investigate the effect of rituximab in this setting, we have performed a multicenter retrospective study in 50 patients with DLBCL re-treated with rituximab in combination with chemotherapy. We have included in this study 46 patients (31 males, 15 females), median age 60 (range, 20 to 81 years), who achieved CR with the previous rituximab-containing regimen. At initial diagnosis, 32 patients had Ann-Arbor stage III or IV and 20 patients had IPI 3 or 4. The median interval between courses was 14.7 months. The most frequent regimens administered as up-front therapy in combination with rituximab were CHOP-like regimens (30 patients) and the commonest chemotherapy regimens used as salvage therapy were R-ESHAP (20 patients), R-ICE (7 patients), rituximab in combination with gemcitabine-based regimens (4 patients) and TTR (3 patients). The overall response rate in the assessable population was 81% (46% CR, 35% PR). In 25 assessable patients who have received rituximab in combination with chemotherapy as second-line therapy, the overall response rate was 92% (56% CR, 36% PR). The overall response rate was slightly lower in those patients re-treated with rituximab as third-line therapy (78% with 33% CR and 45% PR). The follow-up is too shorter (median 6 months) to assess the impact of re-treatment on duration of remission. The adverse events were not different to those usually observed with these regimens. In conclusion, the re-treatment with rituximab in relapsed patients with DLBCL who had respond previously to rituximab in combination with chemotherapy seems not to compromise the results in terms of response. Logically, larger prospective studies are necessary to confirm these encouraging results.