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Background Telomerase disfunction leads to short telometric overhangs, potentially resulting in chromosome instability. Aims To better understand the role of overhang length in the progression of myelodysplastic syndrome (MDS). Methods Bone marrow samples of 62 Chinese MDS patients were screened for TERT and TERC gene variants. Overhangs length was investigated. Results No mutation was identified. MDS patients had shorter overhangs compared to controls. Abnormal karyotype ones had shorter overhang compared to normal. Telomeric overhang length decreased as IPSS/WPSS value increased. Conclusions Overhang changes in accordance with IPSS/WPSS in MDS. Short overhang may be an independent factor for poor prognosis in MDS.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome is a paraneoplastic disorder, of which most clinical manifestations are attributed to elevated vascular endothelial growth factor (VEGF). Osteosclerosis, although well described in the majority of patients, has an obscure mechanism. Although conventional imaging methods, including plain radiography and computed tomography, can be informative, these techniques are neither sensitive nor specific enough to detect the sclerotic changes.1, 2 Markers of bone turnover are easily measured, and when interpreted in the context of appropriate clinical design can provide valuable information. Indeed, increased bone turnover markers were reported in POEMS patients, and have even been suggested for inclusion into the diagnostic criteria.3, 4

Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce.

Neuropathy, the dominant clinical feature of POEMS syndrome, is typically distal, symmetric, and slowly progressive with demyelinating changes. After a gradual proximal spread, it usually results in severe muscle weakness and functional disabilities. Cases characterized by acute onset polyneuropathy are rarely described. In the present report, we describe a 32-year-old male diagnosed as POEMS syndrome, but presenting with a rapidly evolving polyneuropathy. Detailed clinical, electrophysiological, and genetic studies revealed a coexisting underdiagnosed inherited axonal neuropathy, namely Charcot-Marie-Tooth disease 2A2. The patient received lenalidomide-based chemotherapy and consolidated by autologous stem cell transplantation for his POEMS syndrome, which improved the neurological disability. In most conditions, only 1 cause is responsible for a patient's polyneuropathy. However, an insidious inherited neuropathy can be overlooked, when an acquired condition is present. The case illustrated here, to the best of our knowledge, is the first one with coexistent axonal type Charcot-Marie-Tooth disease and POEMS syndrome, suggesting that an unrecognized inherited neuropathy may change the disease course of a further acquired neuropathy.

POEMS syndrome is a rare clonal plasma cell disease. Patients with POEMS syndrome are at risk of developing pulmonary hypertension, but the data on its incidence and impact on outcome are limited. We reviewed records of 154 POEMS syndrome patients with complete duplex echocardiography data for estimation of pulmonary artery systolic pressure (sPAP) at the time of diagnosis. Forty-two (27%) of 154 patients with pulmonary hypertension (estimated sPAP ≥50 mmHg) were identified. Median age was 46 years (range 31-71 years). Patients with pulmonary hypertension were more likely to have peripheral edema (P=0.04), ascites (P=0.02), pleural effusion (P=0.005), and have longer time from onset to diagnosis (P=0.004) when compared with those without pulmonary hypertension. Restrictive abnormalities and decreased diffusion capacity of carbon monoxide were observed in 83% and 96% patients with pulmonary hypertension, compared with 50% and 72% in patients without pulmonary hypertension, respectively. Reversibility of pulmonary hypertension was observed after treatment of POEMS syndrome. After median follow of 32 months, survival of patients with pulmonary hypertension was worse than those without (median overall survival 54 months vs. median not reached, P=0.021). In conclusion, pulmonary hypertension is a common feature of POEMS syndrome, and is associated with signs of extravascular volume overload. Although active treatment of POEMS syndrome can reverse pulmonary hypertension, survival of these patients is worse than those without pulmonary hypertension.

Autologous PBSC transplantation is a preferred treatment for patients with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS syndrome). However, data on stem cell mobilization in POEMS syndrome are limited. We retrospectively reviewed outcomes and factors prognostic of mobilization in newly diagnosed patients with POEMS syndrome. A total of 56 patients (41 men and 15 women) were included and the median age was 45 years (range, 24-62). All patients underwent mobilization with CY plus granulocyte CSF (G-CSF) (n=38) or G-CSF alone (n=18). The median total number of harvested CD34+ cells was 2.01 × 10(6)/kg (range, 0.18-9.0 × 10(6)/kg). In all, 29 (51.8%) patients failed to yield more than 2 × 10(6)/kg CD34+ cells, and among them, 7 (12.5%) patients yielded

Background: POEMS syndrome is a rare plasma cell disorder. The standard treatment of the disease has not been established yet. Although autologous transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, however, many patients will relapse or become refractory to primary therapy. Recently, Anecdotally low dose lenalidomide (10mg, daily) and dexamethasone had good efficacy and safety for patients with refractory or relapsed POEMS syndrome. Prospective clinical data of lenalidomide for POEMS syndrome patients is lacking. We underwent a prospective phase II trial to evaluate the efficacy and safety of low dose lenalidomide and dexamethasone for newly diagnosed patients with POEMS syndrome (NCT01816620). Methods: Patients who met the diagnostic criteria defined by Dispenzieri, with age of 18 years old or more and cytotoxic drug native, were enrolled. All patients received total 12 cycles of low dose Rdex regimen (lenalidomide 10mg/day, on 21 days of a 28-day cycle, plus oral dexamethasone 40 mg/week). Aspirin (100 mg/day) was used for thromboprophylaxis during therapy. Hematologic response was modified from the response criteria of light chain amyloidosis by combined with serum electrophoresis, immunofixation and serum free light chain. The Overall Neuropathy Limitation Scale (ONLS) was used to assess neurological disability. The neurological response was defined as a scale score reduction of at least 1. Serum VEGF levels were measured with a human Quantikine ELISA Kit. The primary endpoint was hematologic and neurologic response. Secondary endpoints included, clinical and serum VEGF response as well as safety. All patients were followed up monthly for the first three months and every 3 months afterwards. Results: Forty-one patients were enrolled from March 2014 to November 2014. The median age was 49 years (range, 21-70) with a male predominance at 68%. All patients had mild to severe polyneuropathy with a median ONLS score of 4 (range, 1-10). The monoclonal components were IgAλ (n = 25), IgGλ (n = 13), λ alone (n=1) and biclonal isotype (n=2). All but one had elevated serum VEGF levels with a median level of 5155 pg/mL (range, 534-14328 pg/mL). Other features including peripheral edema (98%), ascites or pleural effusions (46%), organomegaly (93%), gynecomastia (75%), and skin changes (93%) were also common. All but one patients had completed at least 6 cycles of Rdex therapy. The overall hematologic response was 70% comprised of 47% complete response and 23% partial response. Median time to first hematological response was 2 months (range, 1-9 months). The overall neurologic response was 90.2%. The median ONLS score was decreased from 4 (1-10) to 2 (range, 0-9) and the median time to first neurological response were 1 month (range, 1-9 months). Serum VEGF levels declined significantly from 5155 pg/ml (534-14328 pg/ml) to 1053 pg/ml (447-11864 pg/ml),where 37% and 39% patients achieved VEGF-CR and VEGF-PR, respectively. Rdex was highly effective for patients with extra-vascular volume overload. The initial extra-vascular volume overload responses were observed after a median of 1cycles (range, 1-3) of Rdex therapy. The peripheral edema had disappeared or improved significantly in all patients (100%). Moreover, all three cases (100%) with pulmonary hypertension resolved after lenalidomide therapy. No treatment-related deaths were observed. No patient discontinued therapy because of drug-related adverse events. Only one (2%) grade 3 rash was observed. Regarding hematological toxicity, three patient (7%) experienced grade 2 neutropenia, and three (7%) had grade 1 anemia. Other non-hematological toxicities included grade 1 or 2 elevated ALT level (51%), fatigue (20%), constipation (22%), diarrhea (15%), and rash (10%). Median follow-up time was 10 months (range, 2-14 months). Three patients (7%) had disease progression after 3 (n=1) and 9 (n=2) cycles. Among these three patients, two patients died from respiratory failure due to disease progression and one patient had received salvage therapy of autologous stem cell transplantation. Therefore, one-year progression free survival (PFS) and overall survival (OS) were 83% and 89%, respectively. Conclusion: Combination of low dose lenalidomide and dexamethasone is a effective and safe treatment for patients with newly diagnosed POEMS syndrome. Disclosures No relevant conflicts of interest to declare.

Background In China, the incidence of aplastic anemia (AA) is about 0.74/105, with 0.14/105 of severe aplastic anemia (SAA). Most of these SAA patients are treated in big medical centers or traditional Chinese medicine (TCM) hospitals, which could stand for the current practices in China. Despite the China Aplastic Anemia Consensus, published in 2010, recommended that the immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) were the standard treatment for SAA, very severe aplastic anemia (VSAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA), the current treatment options for patients with these diseases are diverse, including antithymocyte globulin (ATG)/antilymphocyte globulin (ALG) + cyclosporin A (CsA), CSA + androgen, CSA or androgen alone, only supportive care, TCM, etc. This national disease registry study aimed to describe the current clinical practice and treatment patterns for SAA, VSAA and TD-NSAA patients in China and understand their IST patterns as well as the supportive care measures. Methods In this prospective, multi-center, observational study, adult or pediatric patients diagnosed as acquired aplastic anemia within 3 months and met the guideline criteria of SAA, VSAA or TD-NSAA were enrolled from October 2012 to April 2014. All enrolled patients will be followed at least for one year. Each subject will be visited every 3 months in the first year and every 6 months from the second year until the patients withdraw the ICF or study close. The main evaluation criteria is the treatment patterns of SAA, VSAA and TD-NSAA which will be specified as: IST (ATG + CsA, CsA + androgen, CsA and others), HSCT, TCM, androgen, supportive care and others. The response of SAA/VSAA and TD-NSAA after each treatment, and serious adverse events, will also be evaluated by the investigators. An interim analysis is planned when all patients have been enrolled (target N=350) and will focus on their baseline characteristics and first treatment choice. This study was sponsored by Sanofi. Results A total of 352 patients were enrolled at 29 sites in China (SAA 221 pts; VSAA 84 pts; TD-NSAA 47 pts). The median age was 21 years (range, 0-84) and 65.1% were adults. 51.7% were male and 71.6% had ECOG PS Conclusions Chinese AA patients received diverse treatments in real life clinical practice. Based on this interim analysis, 74.1% of the SAA, VSAA and TD-NSAA patients in China received IST. But only 26.4% of them received the standard ATG + CsA therapy. TCM therapy still played a role in the treatment, especially for SAA and VSAA patients in China. Final results including efficacy and safety profiles will be reported later. Disclosures Off Label Use: Anti-thymocyte globulin-Fresenius is used as an immunosuppressive therapy for the treatment of aplastic anemia.

Background : POEMS syndrome is a rare paraneoplastic disorder, characterized by polyneuropathy, organomegaly, osteosclerosis and extravascular volume overload, due to an underlying plasma cell dyscrasia. Vascular endothelial growth factor (VEGF), a potent angiogenic cytokine that can increase vascular permeability, plays a critical role in its pathogenesis. Despite extensive VEGF studies concerning its role in disease diagnosis, monitoring and response assessment, little is known about its cellular source and mechanisms governing the production of VEGF in POEMS patients. Methods and Materials : Patients with POEMS syndrome, 62 newly diagnosed and 46 of them after lenalidomide-dexamethasone (LenDex) treatment, admitted to Peking Union Medical College Hospital between February 2014 and April 2015, were included in the current study. Clinical information, serum and bone marrow samples were collected with the Institutional approval. Serum levels of VEGF were measured by ELISA. VEGF levels in bone marrow plasma cells were quantified via real-time quantitative PCR and multiparameter flow cytometry, respectively. In addition, the phenotype, clonality and intracellular interleukin-6 (IL-6) expression of bone marrow plasma cells were also analyzed by flow cytometry. Furthermore, immunohistochemical staining was performed to study the plasma cell distribution, clonality and expression of VEGF, IL-6 and hypoxia-inducible factor-1α (HIF-1α) in bone marrow biopsies. Statistical analyses were conducted using SPSS 22, and a p < 0.05 was considered as significant. Results : Serum levels of VEGF were dramatically elevated in patients with newly diagnosed POEMS syndrome (median 5958 pg/mL), significantly higher than both disease and healthy controls (p < 0.001), and can be used as a diagnostic marker (area under curve 0.988, p < 0.001). A cut-off value of 2000 pg/mL had a specificity of 97.7% with a sensitivity of 91.9% in support of the diagnosis. After treatment, VEGF levels decreased gradually (6-cycle after LenDex, median 1184 pg/mL, p < 0.001; 12-cycle after LenDex, median 832 pg/mL, p < 0.001). Bone marrow plasma cells showed remarkable VEGF expression, validated in both mRNA and protein levels, which also decreased in response to LenDex therapy. More importantly, a statistically linear correlation was observed between serum and bone marrow plasma cell VEGF levels (newly diagnosed patients, rho = 0.33, p = 0.01; post-therapeutic patients, rho = 0.53, p < 0.001), supporting that bone marrow plasma cells were the source of circulating VEGF. Intriguingly, immunophenotying revealed that bone marrow plasma cells were polyclonal in most newly diagnosed cases. Monoclonal population, co-existing with polyclonal plasma cells, was observed only in 11 patients (18%). Further analyses showed that the relative amounts of these two populations were similar (41% vs. 59%) and they also had comparable intracellular VEGF expression (mean fluorescent intensity, 2009 vs. 2367, p = 0.594). However, monoclonal plasma cells had significantly higher intracellular IL-6 expression (mean fluorescent intensity, 1635 vs. 865, p = 0.006). In 46 newly diagnosed cases with bone marrow biopsies available, immunohistochemical staining was performed, and plasma cells were typically distributed in a scattered manner, with focal aggregates observed in 21 cases (46%). Intracellular κ and λ light chain staining demonstrated that the background scattered plasma cells were polyclonal, while both monoclonal and polyclonal fractions were observed in the focal area, which showed similar nuclear and intracellular staining of HIF-1α and VEGF, respectively. In contrast, IL-6 was mainly expressed in λ-restricted plasma cells. Conclusion : Bone marrow plasma cells are the potential source of VEGF production in patients with POEMS syndrome. Monoclonal plasma cells, aggregates focally in the bone marrow, may secret IL-6 to stimulate polyclonal plasma cells proliferation, and consequent VEGF production in a paracrine circuit. Disclosures Off Label Use: Lenalidomide for POEMS syndrome.

Background Chidamide (CS055) is a new oral benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10, and it has been approved for relapsed or refractory peripheral T-cell lymphoma (PTCL) in China. This phase II study (ChiCTR-TNC-00000806) was to evaluate the efficacy and safety of chidamide in different dosing regimens in patients with relapsed or refractory cutaneous T-cell Lymphoma (CTCL). Methods Fifty-two patients, all were mycosis fungoides or Sezary syndrome, were enrolled in this study. In the first stage of the study, 26 patients were randomly assigned to receive chidamide 30 mg twice per week for 2 weeks out of a 3-week-cycle (13 patients), or 4 weeks out of a 6-week-cycle (13 patients). Another 26 patients were enrolled in the second stage, and were treated by chidamide of 30 mg twice per week without drug-free holiday. The primary endpoint was objective response rate (ORR). Responses were evaluated based on the overall skin lesions, lymph nodes, blood cells and pruritis. Results The ORRs were 33% (4/12 PRs) for the 3-week-cycle arm, 23% (3/13 PRs) for the 6-week-cycle arm, and 36% (1/25 CR + 8/25 PRs) for the successive dosing arm, respectively. Median duration of response (DOR) was 50, 92, and 169 days for the indicated 3 arms, respectively. Twelve (92%), 11 (85%) and 20 (77%) patients experienced adverse event (AE) in the three arms. Most AEs were in Grade 1 or 2. Thrombocytopenia, leucopenia, fatigue, nausea and diarrhea were most frequently seen. Two serious adverse events (SAE) were reported in the study. One patient in the 3-week-cycle arm was hospitalized for fever and lung infection, and the other in the successive dosing arm was hospitalized for hyperglycemia. Conclusions Chidamide was active and tolerable to relapsed or refractory CTCL. The ORR of chidamide was comparable with the marketed drugs for CTCL. The major toxicities of chidamide were hematologic and gastrointestinal reactions which were controllable. Based on the overall profiles of the three different dosing regimens, 30 mg twice per week successively was clinically recommended. Table 1. Efficacy 3-week-cycle arm(N=12) * 6-week-cycle arm (N=13) Successive dosing arm(N=25) * CR 0 0 1 PR 4 3 8 ORR (%) 4 (33) 3 (23) 9 (36) Median DOR (days) 50 92 169 Median PFS (days) 84 81 88 *patients with ineligible entrance of the study were excluded for the efficacy analysis Table 2. Safety 3-week-cycle arm (N=13) 6-week-cycle arm (N=13) Successive dosing arm (N=26) Patients with AE (%) 12 (92) 11(85) 20 (77) Patients with AE ≥grade 3 (%) 3 (23) 5 (38) 4 (15) Patients with SAE (%) 1 (8) 0 1 (4) AEs in ≥10% of patients (%) Thrombocytopenia 5 (39) 3 (23) 9 (35) Leucopenia 7 (54) 4 (31) 4 (15) Fatigue 3 (23) 3 (23) 3 (12) Nausea 3 (23) 1 (8) 3 (12) Diarrhea 1(8) 1 (8) 3 (12) Fever 0 2 (15) 2 (8) Anemia 1 (8) 2 (15) 1 (4) Disclosures No relevant conflicts of interest to declare.

POEMS syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. This study reviewed the clinical characteristics and long-term outcome of 99 consecutive Chinese patients with newly diagnosed POEMS syndrome in a single institute. The median age of 99 patients was 45 years, and the ratio of men/women was 1.4. The median time from onset of symptoms to diagnosis was 18 months. The typical five features of peripheral neuropathy, organomegaly, endocrinopathy, M protein, and skin change remained to be essential for patients with POEMS syndrome in China. The unusual features like pulmonary hypertension (36%) and renal impairment (37%) were not uncommon in China. Eighty-three percent patients were alive after follow-up time of 25 months, and 10% patients had survived more than 60 months. Melphalan-based therapy (OR, 0.076; 95% CI, 0.02–0.285) and normal renal function (OR, 0.246; 95% CI, 0.076–0.802) were independent prognostic factors for the survival of patients with POEMS syndrome. In conclusion, POEMS syndrome in Chinese patients was a multi-systemic disease with clinical features similar to non-Chinese ones. Active therapy can effectively improve the prognosis of patients with POEMS syndrome.

Background Renal impairment is a common complication of multiple myeloma (MM) and is related to shorter overall survival and increased rates of early death. Bortezomib is a new agent for the treatment of patients with myeloma, with high response rates and controllable side effects. In this study, we will evaluate the efficacy and safety of bortezomib and dexamethasone in patients with newly diagnosed MM complicated by renal impairment. Patients and Methods This is a prospective study of the general characteristics, reversibility of renal impairment, response of myeloma, and side effects of 18 consecutive newly diagnosed patients with MM and renal impairment who received ≥ 2 cycles of bortezomib and dexamethasone. Results Of 18 patients newly diagnosed with MM, the median age was 60 years, and the median serum creatinine was 5.3 mg/dL. Patients received a median of 4 cycles of bortezomib and dexamethasone. Reversal of renal impairment was documented in 38.9% of the patients, and the median time to reversal was 16 days. Moreover, 33.3% of the patients achieved renal response (a 50% decrease in serum creatinine). The overall response rate of MM was 83.3%, including a 33.3% complete response (CR) rate, a 16.7% near-CR rate, a 16.7% very good partial response (PR) rate, and a 16.7% PR rate. Grade 3/4 adverse events consisted of infection (n = 3), peripheral neuropathy (n = 3), and ileus (n = 1). After a median follow-up of 15.7 months, the median progression-free survival for all patients was 12.6 months. Conclusion Bortezomib plus dexamethasone is a safe and effective regimen for newly diagnosed patients with MM complicated by renal impairment.

We determined the best extraction buffer for proteomic investigation using formalin-fixation and paraffin-embedded (FFPE) specimens. A Zwittergent 3–16 based buffer, sodium dodecyl sulfate (SDS)-containing buffer with/without polyethylene glycol 20000 (PEG20000), urea-containing buffer, and FFPE-FASP protein preparation kit were compared for protein extraction from different types of rat FFPE tissues, including the heart, brain, liver, lung, and kidney. All of the samples were divided into two groups of laser microdissected (LMD) and non-LMD specimens. For both kinds of specimens, Zwittergent was the most efficient buffer for identifying peptides and proteins, was broadly applicable to different tissues without impairing the enzymatic digestion, and was well compatible with mass spectrometry analysis. As a high molecular weight carrier substance, PEG20000 improved the identification of peptides and proteins; however, such an advantage is limited to tissues containing submicrograms to micrograms of protein. Considering its low lytic strength, urea-containing buffer would not be the first alternative for protein recovery. In conclusion, Zwittergent 3–16 is an effective buffer for extracting proteins from FFPE specimens for downstream proteomics analysis.

PO-392 Safety of Lenalidomide (LEN) Plus Low-Dose Dexamethasone (DEX; Rd) in Chinese Patients (Pts) With Relapsed/Refractory Multiple Myeloma (RRMM) Treated With Prior Thalidomide (THAL) and Bortezomib (BORT): Subanalysis of the MM-024 Extended Access Program (EAP) L. Yu, Z. Cai, J. Jin, X. Du, F. Chen, D.-b. Zhou, X. Ke, X. Li, D. Wu, F. Meng, D. DeMarco, J. Zhang, J. Mei, J. Hou The 301 Hospital-Chinese PLA General Hospital, Beijing, China; The First Affiliated Hospital, Zhejiang University, Hangzhou, China; Guangdong General Hospital, Guangzhou, China; Xiangya Hospital of Central South University, Changsha, China; Peking Union Medical College Hospital, Beijing, China; Peking University 3rd Hospital, Beijing, China; Shanghai 6th Hospital, Shanghai, China; The 1st Affiliated Hospital of Soochow University, Suzhou, China; Nanfang Hospital of Southern Medicine University in Guangzhou, Guangzhou, China; Celgene Corporation, Summit, NJ, USA; Department of Hematology, Shanghai Changzheng Hospital, Shanghai, China Introduction: The efficacy and safety of Rd (LEN 25 mg/day on D1e21 and low-dose DEX 40 mg/day on D1, 8, 15, and 22 of each 28-day cycle) given until progressive disease or discontinuation of LEN for any reason in Chinese pts with RRMM was demonstrated in the multicenter phase 2 MM-021 trial (Hou J, et al. J Hematol Oncol. 2013;6:41). Pts in MM-021 received a median of 4 (range 1e15) prior antimyeloma treatments (Tx) with 90 (45%) pts treated with both THAL and BORT. MM-024 is an EAP for Table Pt baseline characteristics and selected safety outcomes wi THAL (n [ 18) BO (n [ Baseline characteristics, n (%) Age > 65 yrs 4 (22) 3 (1 ECOG performance status score 2 1 (6) 0 Durie-Salmon stage III 12 (67) 14 ( 5 prior Tx 6 (33) 4 (2 Gr 3e4 AEs, n (%) Any Gr 3e4 AE 13 (72) 8 (5 Neutropenia 4 (22) 1 ( Anemia 3 (17) 0 Thrombocytopenia 0 0 Pneumonia 2 (11) 2 (1 Fatigue 2 (11) 0 Peripheral neuropathy 0 1 ( Deep-vein thrombosis 0 0 AE, adverse event; gr, grade. Includes pneumonia, lobar pneumonia, and bronchopneumonia. MM-021, and was designed to monitor the long-term safety of Rd. The aim of this subanalysis of the MM-024 EAP was to investigate the long-term safety of Rd in Chinese pts with RRMM previously treated with both THAL and BORT, or treated with neither THAL nor BORT. Patients and Methods:MM-024 pts received the same Rd regimen as those in the MM-021 study. Starting doses of Rd were the same as the last doses received in MM-021 unless dose adjustments were required prior to rollover, per protocol. Tx continued until disease progression, withdrawal due to toxicity, or lost to follow-up, and pts were followed for up to 5 years (yrs; including 1 yr spent in MM-021). The primary endpoint was safety. Results: Of the 80 pts enrolled in MM-024, 18 (23%) had received prior Tx with THAL, 16 (20%) prior Tx with BORT, 41 (51%) prior Tx with both THAL and BORT, and 5 (6%) prior Tx with neither THAL nor BORT (data cutoff November 5, 2014). Baseline characteristics were generally similar across prior Tx subgroups (Table); as expected, pts who had received prior Tx with THAL and BORT were more likely to have received multiple prior Tx. The incidences of Gr 3e4 neutropenia, anemia, and thrombocytopenia AEs were generally similar across subgroups (Table). Gr 3e4 pneumonia was reported in about 10% of pts with prior THAL, BORT, or both THAL and BORT. Rates of Gr 3e4 peripheral neuropathy and deep-vein thrombosis were low. No pts discontinued Rd due to AEs; however, 2 pts died due to Tx-related AEs: 1 had received prior THAL only (lung infection), and 1 had received prior THAL and BORT (cerebral infarction). The safety profile of Rd in pts with prior THAL and BORT was consistent with the overall safety results from the MM-024 and MM-021 trials. Conclusion: Results of this subgroup analysis suggest that Rd has an acceptable long-term safety profile in Chinese pts with RRRM, regardless of prior Tx with THAL and/or BORT. This abstract was developed with editorial support from Excerpta Medica. th Rd, according to prior Tx subgroups RT 16) THAL and BORT (n [ 41) Neither THAL nor BORT (n [ 5) 9) 15 (37) 1 (20) 3 (7) 1 (20) 88) 33 (81) 5 (100) 5) 23 (56) 1 (20)

BACKGROUND Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a multisystem disorder arising from underlying plasma cell dyscrasia. Renal impairment and related pathological changes have been reported, but data on its prevalence, response to therapy and impact on survival are still lacking. METHODS We retrospectively reviewed 299 patients diagnosed with POEMS syndrome in a tertiary-care university hospital from 2000 until 2014. The estimated glomerular filtration rate (eGFR) was used to define renal impairment and response, according to International Myeloma Working Group criteria. We examined the impact of renal impairment and response on patient survival. RESULTS Sixty-seven patients (22.4%) had renal impairment (eGFR < 60 mL/min/1.73 m(2)) at baseline. In a multivariate analysis, ascites was independently associated with renal impairment [odds ratio (OR) 12.366, P < 0.001]. Renal impairment was reversible in 66.0% of patients receiving therapy and was associated with a shorter time interval between symptom onset and treatment (OR 0.059, P = 0.043) and a vascular endothelial growth factor remission (OR 15.958, P = 0.050) in a multivariate analysis. In terms of therapy, patients with a renal response more commonly received a novel agent-based regimen (P = 0.037), which also led to a shorter response time (P = 0.001). With a median follow-up of 27.4 months, inferior survival was observed in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m(2)), but not in those with moderate dysfunction (eGFR 30-59 mL/min/1.73 m(2)), compared with patients without renal impairment. A renal response, if achieved, predicted improved survival. CONCLUSIONS Renal impairment is a common complication of POEMS syndrome, but can be reversed with effective therapy in most cases.

Introduction: In China, the Rd regimen is approved for use in multiple myeloma (MM) pts who have received ≥ 1 prior treatment (Tx). This approval was based on the efficacy and safety of Rd demonstrated in the MM-021 study, a phase 2 multicenter registration trial in which 199 pts were enrolled (Hou, J Hematol Oncol 2013). MM-024 is both an EAP and an extension study that was initiated in order to provide continued Rd regimen for pts enrolled in the MM-021 study. Updated safety and efficacy information from the EAP is presented here. Methods: Eligible pts had participated in MM-021, were still on Tx for ≥ 1 year (yr) and were progression-free. Pts received the same regimen of Rd as in MM-021 (lenalidomide 25 mg/day on days 1–21, and low-dose dexamethasone 40 mg/day on days 1, 8, 15, and 22 of each 28-day cycle). The starting doses of Rd were the same as the last doses received in MM-021 unless dose adjustments were required prior to rollover, as per protocol. Tx was continued until progressive disease (PD) or withdrawal due to toxicities, and pts were followed-up for a maximum of 5 yrs (which included 1 yr spent in the MM-021 study). The primary endpoint was safety, including the incidence of second primary malignancy (SPM). Secondary endpoints included progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Results: By the cutoff date (May 5th, 2014), of the 41 pts who entered the Tx phase of the EAP, 21 are still receiving Tx with a median number of 22 cycles. A total of 20 pts discontinued Tx: 18 discontinued due to PD; 1 due to death (related to lung infection); and 1 was lost to follow-up. Median follow-up was 37.5 months (mos) from initial enrolment in the MM-021 study. Median age was 59 yrs (range 47–74) and 34% of pts were aged > 65 yrs. Most pts (78%) had Durie-Salmon stage III disease at baseline. All pts had received prior Tx for MM, including thalidomide and bortezomib; 7.3% of pts had undergone surgery and 2.4% of pts had received radiation therapy. The median number of prior Tx was 3 (range 1–11); 76% of pts had received prior bortezomib, 68% had received prior thalidomide, and 46% had received both. Median duration of Rd Tx was 21.6 mos (range 13.1–37.5) and 22% of pts have received > 25 mos of the regimen. All efficacy endpoints were measured from the enrolment date of the MM-021 study. Median PFS and median TTP were both 36.0 mos. Median OS has not been reached due to the low number of deaths. Overall, 48.8% of pts had grade 3–4 treatment-emergent adverse events (TEAEs); the most common TEAEs were anemia (51.2%), decreased neutrophil count (48.8%), upper respiratory tract infection (41.5%), neutropenia (31.7%), cough (24.4%), diarrhea (22.0%), and pyrexia (22.0%). Grade ≥ 3 TEAEs included neutropenia (14.6%), anemia (4.9%), thrombocytopenia (2.4%), and pneumonia (7.3%). No TEAEs led to Tx discontinuation; however, TEAEs led to lenalidomide dose reduction (14.6%), interruption (39%), or both (14.6%). Updated efficacy, survival, and SPM analysis will be presented at the meeting. Conclusions: After 37.5 mos of follow-up, median PFS was 36 mos, compared with the median PFS of 7.5 mos in the MM-021 final analyses (cutoff date January 4th, 2013). This indicates that long-term use of Rd is well tolerated and continues to be an effective Tx in Chinese pts with RRMM who have received multiple prior Tx. Disclosures DeMarco: Celgene Corporation: Employment. Zhang:Celgene Corporation: Employment. Mei:Celgene Corporation: Employment. Hou:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees.

To explore the efficacy, safety and immune reconstitution of autologous peripheral blood stem cell transplantation (APBSCT) using T cell depleted grafts in the treatment of refractory rheumatoid arthritis (RA).One patient with RA was treated with APBSCT. The method included mobilization with 2 g/m(2) cyclophosphamide (CY) and subcutaneous injection of granulocyte-colony stimulating factor (G-CSF). Immunomagnetic selection of CD34(+) cells from the leukapheresis products was performed to deplete potentially autoreative lymphocytes. The conditioning regimen consisted of intravenous administration of 2 g/m2 CY and 90 mg/kg ATG, with subsequent reinfusion of the graft. G-CSF was used to help hematopoietic and immunologic reconstitution. Phenotype of the peripheral blood lymphocytes was analyzed to observe the immunologic reconstitution after transplantation.The patient completed the mobilization, conditioning regimen and transplantation successfully. The hematologic recovery was rapid and the patient achieved clinical remission. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) decreased to normal level and the rheumatoid factor (RF) turned negative after a follow-up of 12 months. An ongoing course of immunologic reconstitution was observed.APBSCT is effective and safey for refractory RA, and can induce improvement of disease activity. The course of immunologic reconstitution after transplantation remains to be observed in long-term followup.

Background Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated rapid and durable reductions in splenomegaly, improved MF-related symptoms and quality of life (QoL), and prolonged survival in 2 phase 3 studies comparing ruxolitinib with placebo (COMFORT-I) and best available therapy (COMFORT-II). However, no clinical trial in pts with MF had been conducted in Asian countries, and only a limited number of Asian pts or healthy volunteers had been enrolled in any ruxolitinib study. Methods This study was an open-label phase 2 study evaluating ruxolitinib in Asian pts with PMF, PPV-MF, or PET-MF who had palpable splenomegaly ≥ 5 cm below the costal margin and intermediate-2– or high-risk MF by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Pts received starting doses of ruxolitinib 15 or 20 mg twice daily (bid) based on baseline platelet count (100-200 or > 200 × 109/L, respectively); dose adjustments balancing safety and efficacy were allowed to titrate each pt to their most appropriate dose. The primary endpoint was met if the proportion of pts achieving ≥ 35% reduction in spleen volume from baseline at week 24 was ≥ 27.5% as measured by MRI/CT. Symptomatic response was assessed as a secondary endpoint using the 7-day modified MF Symptom Assessment Form (MFSAF) v2.0 total symptom score (TSS) and European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30). The study was conducted in China (n = 63), Japan (n = 30), Korea (n = 17), and Taiwan (n = 10). The data cutoff date for this analysis was 7 June 2013. Results Overall, 120 pts were enrolled (PMF, n = 80; PPV-MF, n = 21; PET-MF, n = 19), and their baseline characteristics were as follows: median age, 61 years (range, 25-80 years); 51.7% female; 69.2% intermediate-2 and 30.8% high risk by IWG-MRT criteria; median palpable spleen size, 15 cm (range, 5-45 cm); median spleen volume, 2159 cm3; 55.8% of pts had prior exposure to hydroxyurea. The median follow-up was 8.44 months; 22.5% of pts discontinued treatment, primarily for adverse events (AEs; 9.2%) and disease progression (7.5%). The median duration of treatment was 8.44 months (range, 0.5-21.7 months), and the median daily dose was 20.64 mg/day in the 15 mg bid group (n = 46) and 36.11 mg/day in the 20 mg bid group (n = 74). All pts were evaluable for achievement of the primary endpoint, 101 pts remained on study and were evaluable at week 24, and 96 pts had nonzero scores on the MFSAF-TSS and were evaluable for a reduction from baseline. Most pts who had assessments at week 24 (91% [92/101]) had a reduction from baseline in spleen volume (Figure). The study met the primary endpoint, with 31.7% (38/120) of all pts achieving ≥ 35% reduction from baseline at week 24. Overall, 38.3% (46/120) of pts achieved ≥ 35% reduction from baseline in spleen volume at any time on study. As measured by the 7-day MFSAF, 49% (47/96) of pts achieved ≥ 50% reduction from baseline in TSS (median reduction, 47.2%). Pts experienced an improvement from baseline at week 24 in EORTC global health status/QoL (mean change, 5.2). The most common nonhematologic AEs (≥ 10%) regardless of relationship to study medication included diarrhea (25.8%), upper respiratory tract infection (17.5%), ALT level increased (15.0%), pyrexia (15.0%), AST level increased (13.3%), cough (11.7%), herpes zoster infection (11.7%), nasopharyngitis (10.8%), constipation (10.0%), gamma-glutamyl transferase level increased (10.0%), and headache (10.0%), and most were grade 1/2. Serious AEs were reported for 24.2% of pts, and 65.8% of all pts had grade 3/4 AEs. The most common new or worsening laboratory abnormalities were low hemoglobin (all grade 3, 55.7%), low lymphocyte (grade 3/4, 19.5%), low platelet (grade 3/4, 15.3%), and low ANC (grade 3/4, 7.6%) levels. AEs observed in this study were consistent with those observed in the 2 large phase 3 COMFORT studies. Six pts (5%) died on treatment or within 30 days of discontinuation. Summary/conclusions Findings from this study demonstrated that ruxolitinib was relatively well tolerated in Asian pts with MF and provided substantial reductions in splenomegaly and modest improvements in MF-associated symptoms. The AEs observed with ruxolitinib treatment in this study are consistent with those observed in the large phase 3 COMFORT studies, and there were no new AEs associated with ruxolitinib in Asian pts with MF. Disclosures: Okamoto: Novartis: Honoraria, Research Funding. Sirulnik:Novartis: Employment. Ruiz:Novartis: Employment. Amagasaki:Novartis: Employment. Ito:Novartis: Employment. Akashi:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Abstract 1824 Background and Object About 80% patients with multiple myeloma (MM) represent destructive bone disease, which is negatively correlated with life quality and survival. The mechanism of myeloma bone disease involves the enhancement of bone absorption accompanied with inhibition of bone formation, namely, over-activated osteoclasts and suppressed osteoblasts. Our previous data have shown that serum level of stromal cell derived factor 1 alpha (SDF-1 α), secreted by bone marrow stromal cells (BMSCs) for stem cell homing, was positively correlated with the serum level of dickkopf-1 (DKK-1), a soluble inhibitor of Wnt signaling pathway which plays an important role in osteoblast differentiation and proliferation. To further reveal the pathogenesis of MM bone disease, this study was to explore the mechanism how SDF-1α and DKK-1 interact to promote myeloma bone disease. Materials and Methods Forty six untreated MM patients were included in our study. The clinical data, sera and bone marrow aspirates were collected. Serum SDF-1α and DKK-1 were tested using ELISA kits. Plain radiographs were used to assess osteolytic lesions. The relationship between the severity of bone disease and serum values of SDF-1α and DKK-1 was analyzed. Human MM cell line RPMI 8226 was cultured in vitro. Under the condition of SDF-1α 10ng/ml, the transcription level of DKK-1 was detected at 8h and 36h by Realtime PCR relative quantitation SYBR technique. Myeloma cells from patients' bone marrow were sorted by CD138 immunomagnetic beads. The purity of sorted cells was detected by flowcytometry. The transcription level of DKK-1 in primary myeloma cells was tested after stimulation of SDF-1α for 72 hours. BMSCs from MM patients were cultured in vitro. When added with Wnt-3a (200ng/ml) and/or DKK-1 (20ng/ml), the transcription level of SDF-1 alpha was assayed. Statistics was carried out using SPSS Statistics 17.0. P value of less than 0.05 was considered as significance. Results The serum level of SDF-1α in MM patients (n=46) was significantly higher than that of the age-matched health control (n=30) (3275.9±1093.0pg/ml vs 2817.5±419.6pg/ml, P=0.015). The serum level of DKK-1 in MM patients was also significantly higher than that of the health control (3275.9±1093.0pg/ml vs 1494.2±918.7pg/ml, P=0.025). There was a positive relationship between serum SDF-1 alpha and DKK-1 in MM patients (r=0.40, P=0.001). However, such association did not show in health control group(r=0.15,P=0.428). Patients with positive radiological findings had higher level of SDF-1α compared to negative patients (2989±838 pg/ml vs 2460±739 pg/ml, respectively) with no statistically difference. Serum DKK-1 was also higher in patients with positive bone disease, which was 5072±8032pg/ml compared to 1032±720pg/ml in patients with negative findings (P=0.18). Both SDF-1α and DKK-1 had the increasing trend according to more advanced stage of ISS, yet with no statistical difference. After stimulation of SDF-1α for 8h and 36h in RPMI 8226 cell line, the mRNA of DKK-1 was increased by 1.92 and 4.19 folds respectively (P=0.099). The purity of CD138 positive myeloma cells was 99.5%. Primary myeloma cells from 9 MM patients had a wide range of DKK-1 relative expression from 0.06% to 11.09% contrasted to the house keeping gene of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Myeloma cells with higher baseline DKK-1 transcription level (higher than 0.2%) seemed to be more susceptible to extra SDF-1α, which leads to significantly upregulated DKK-1 expression (P=0.043). However, upregulation of DKK-1 was not seen in cells with low baseline DKK-1 expression. When BMSCs exposed to Wnt-3a, it showed that SDF-1α mRNA was significantly down regulated to 29% (P=0.028). However, this effect was reversed with the co-existence of DKK-1 and Wnt-3a. Conclusion The serum levels of both SDF-1α and DKK-1 were elevated in MM patients with positive correlation. The severity of clinical bone disease has the trend to parallel to SDF-1α and DKK-1. SDF-1α enhanced mRNA transcription level of DKK-1 in both myeloma cell line and primary myeloma cells, while DKK-1 promoted the transcription of SDF-1α in BMSCs. SDF-1α and DKK-1 interacted with each other as a vicious cycle to facilitate myeloma bone disease. It would be a new target to interrupt the communication of SDF-1α and DKK-1 for treating myeloma bone disease. Disclosures: No relevant conflicts of interest to declare.

Abstract 5046 Introduction: Lenalidomide (LEN), in combination with dexamethasone (DEX), has been approved in many countries for treatment of MM in pts who have received ≥1 prior therapy. The PK of LEN has been previously evaluated in Caucasian and Japanese pts with MM. However, its ethnic sensitivity has not been investigated elsewhere. MM021 is the first study in China to evaluate the PK of LEN, when administered alone or in combination with DEX, in Chinese pts with RRMM. The PK results obtained from this study were compared with those historically observed in Japanese/Caucasian MM pts. Patients and Methods: MM021 is a phase 2, multicenter, open-label study to assess the efficacy and safety of LEN + DEX. A subset of Chinese MM pts aged ≤75 years who were eligible to receive DEX at the starting dose of 40 mg were included in the PK assessments of this study. In treatment cycle 1, these pts received oral LEN 25 mg/d on Days 1–21, and 40 mg oral DEX on Days 8, 15, and 22. Serial plasma sampling for PK analysis was performed 24 hours (hrs) after the LEN dose on Days 1, 7, and 8. LEN PK in the absence of DEX was evaluated after a single dose (Day 1) and after multiple doses (Day 7). The effect of DEX was evaluated by comparing the multiple doses of LEN in the absence (Day 7) and presence (Day 8) of DEX. To compare systemic LEN exposures among ethnic groups, the maximum concentration (Cmax) and area under the concentration-time curve from time zero extrapolated to infinity (AUC∞) observed in Japanese and Caucasian MM pts were normalized to the levels at 25 mg. Plasma concentration of LEN was determined by validated liquid chromatography mass spectrometry (LC-MS/MS) assay. Results: A total of 11 Chinese MM pts were enrolled for PK analysis. These pts were mostly male (72%), with a median age of 56 yrs (range 44–68) and median body weight of 66 kg (range 54–84). The median creatinine clearance (CrCL) estimated by Cockcroft-Gault formula at baseline was 86 mL/min (range 42–154). When administered alone to Chinese MM pts, LEN was absorbed rapidly, with a median time of approximately 1 hr to reach Cmax. Consistent with a mean terminal half-life (t1/2) of approximately 3 hrs and a dosing interval of 24 hrs, LEN did not accumulate in plasma with multiple doses (Figure 1). There was no time-dependence in t1/2 and apparent total clearance (CL/F), supporting the linear PK. In 1 pt who had moderate renal impairment (CrCL = 42 mL/min), LEN AUC∞was increased by approximately two-fold, compared with the mean value for all pts. The mean LEN plasma concentration vs. time profile in the presence of DEX was almost identical to that in the absence of it (Figure 1). The 90% confidence interval for the ratio of geometric means between LEN alone and LEN + low-dose DEX was contained within the equivalence limits of 80% and 125% for both Cmax and AUC. Since the elimination of LEN is primarily renal, comparison of LEN PK parameters among ethnic groups was done only in pts with CrCL ≥60 mL/min (Table 1). Mean plasma AUC∞ in Chinese MM pts administered 25 mg LEN (2202 h·ng/mL) was comparable to that historically observed in Japanese and Caucasian MM pts (2305 and 2124 h·ng/mL, respectively), with a similar inter-patient variability of approximately 25–30%, even though Chinese pts had a lower median body weight compared with Caucasian pts. There was also no difference observed in other PK parameters between Chinese, Japanese, and Caucasian MM pts (Table 1). Conclusion: Co-administration with DEX has no effect on the PK of LEN. There are no apparent ethnic differences in the PK of LEN among Chinese, Japanese, and Caucasian MM pts. Only pts with CLcr >= 60 mL/min are included; median (range) are presented for age, body weight, CrCL and Tmax; geometric mean (CV%) data are presented for other parameters. Disclosures: Chen: Celgene Corporation: Employment. Mei:Celgene Corporation: Employment. Liu:Celgene Corporation: Employment. Wang:Celgene Corporation: Employment. Wortman-Vayn:Celgene Corporation: Employment. Hou:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Xian: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jensen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Abstract 1864 Background: Previous studies (i.e. ECOG E4A03) have shown that lenalidomide plus low-dose dexamethasone (Rd) has a better safety profile compared with lenalidomide plus high-dose dexamethasone (RD) in newly diagnosed MM patients. It is hypothesized that Rd may also provide benefits in patients with relapsed/refractory multiple myeloma (RRMM). The MM-021 trial is the largest study in Chinese patients with RRMM aimed to assess the efficacy, safety, and pharmacokinetics (PK) of Rd in patients who had progressed or were refractory to previous treatment. Methods: This was a phase II, multi-center, single arm, open-label study, RRMM patients received lenalidomide (25 mg/day on days 1–21) and dexamethasone (40 mg on days 1, 8, 15 and 22) in 28-day treatment cycles until disease progression. Thromboembolic prophylaxis with aspirin or other anti-thrombotic medication was required. The primary endpoint was the best overall response rate (partial response [PR] or better) based on the investigator's assessment. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), safety, and PK parameters. Results: As of April 23, 2012 (median follow-up of 10.8 months), 199 patients have completed at least 1 cycle, 134 patients have completed at least 6 cycles, and 187 patients were evaluable for efficacy. Median age was 59 years (range 35–81) and 63% were male. The majority of patients (86%) had Durie-Salmon stage III disease and 57% had received ≥4 prior anti-myeloma regimens including bortezomib (64%), thalidomide (69%), or both bortezomib and thalidomide (45%). After median treatment duration of 8 months (range 1–18) or 8 cycles (range 1–19), best overall response rate (≥PR) was 54% (100 patients); including 8% (14 patients) with a best response of complete response (CR). Overall disease control (≥stable disease [SD] or better) was 95%, including 42% (78 patients) with best response of SD. Nine patients (5%) had best response of disease progression. Best overall response rates were consistent across subgroups when analyzed according to baseline renal function (creatinine clearance ≥60 mL/min: 68 patients [54%], 330 to 2 prior regimens). Responses were also consistent regardless of prior therapy received; 50%, 52%, and 47% for patients who previously received bortezomib, thalidomide, or both, respectively. Of the 5% (10 patients) presenting with IgD at baseline, 7 patients achieved ≥PR. Median time to first response was 2 months (range 1–12) and median duration of response was 7 months (range 0–16). The median PFS was 8 months (95% CI: 6–9) and the OS rate was 86% at 6 months and 73% at 1 year. Among the 199 patients evaluable for safety, the most common grade 3–4 adverse events (AEs) were anemia (25%), neutropenia (24%), thrombocytopenia (15%), and pneumonia (13%). Only 1 patient experienced febrile neutropenia. AEs led to dose reduction/interruption of lenalidomide in 40% of patients, 41% for dexamethasone; and 6.5% discontinued treatment due to one or more AEs. No patient discontinued due to anemia or neutropenia. Sixty-one patients (31%) died on study and the most common cause of death was disease progression (15 patients, 8%). Conclusions: Based on a median follow-up of nearly 11 months, the Rd regimen achieved a substantial best overall response rate (54%) in heavily pretreated RRMM Chinese patients. Response rates were consistent across subgroups including patients with renal impairment. The combination of Rd regimen was generally well tolerated. Disclosures: Hou: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Xian: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jensen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mei:Celgene Corporation: Employment. Zhang:Celgene Corporation: Employment. Wortman-Vayn:Celgene Corporation: Employment.

Primary CNS lymphoma (PCNSL) is an uncommon and progressive form of non-Hodgkin’s lymphoma. Since the majority of PCNSL cases are B-cell neoplasms expressing the CD20 surface antigen, treatment with Rituximab, the anti-CD20 antibody, might be a new therapeutic option. Since 2000, we have been performing a study on PCNSL patients with combined treatment of intraventricular immunochemotherapy and systemic chemotherapy. Ommaya reservoirs were placed in all these patients. The regimen of Intraventricular therapy is as follows: Methotrexate (MTX) 10mg plus Dexamethasone (Dex) 5mg followed by Cytosine arabinoside 25mg plus Dex 5mg via Ommaya reservoir in the first week, and Rituximab30mg plus Dex 2mg were given via Ommaya reservoir every other day for three times in the second week. Above treatments were finished 2 weeks a cycle until complete response (CR) was achieved and then the interval prolonged. Systemic chemotherapy includes regimen A and B. Regimen A: MTX 3~5g/m2 (D1), Vincristine 2mg (D1), Ifosfomide (IFO) 800mg/m2 (D2~4), and Dex. 10mg/m2 (D2~4). Serum MTX levels were monitored and Leucovin rescue began 24 hours after completion of MTX. Mesna rescue for IFO were also given conventionally; Regimen B: Carmustine 125 mg (D1), Teniposide 50mg (D1~3), Vindesine 4mg (D1), and Dex. 20mg (D1~4). Regimen A and B were given alternatively three weeks a cycle until CR was achieved, and then the interval prolonged. Brain MRI or PET was done every 2 or 3 months after treatment for evaluation of the response. Seven patients have been evaluated. The patients are 5 males and 2 females with the mean age of 51 years old (range: 32–82). One of the cases was a relapsed PCNSL who had achieved CR1 after whole-brain radiotherapy, systemic chemotherapy and autologous peripheral blood stem cell transplantation. He relapsed 33 months after CR1 and was enrolled in this study. After therapy he achieved CR2. But the second relapse occurred 18 months after CR2, and CR3 was achieved again after treatment with the same regimens, and total survival time has been 83 months. The other six cases were newly diagnosed PCNSL and all achieved CR after 2 to 3 months’ treatment. Among them only one patient experienced relapse after 26 months of remission, regimen A and intraventricular Rituximab were given but showed no remarkable response and died with survival time of 29 months. Other five patients are in continuing CR for 2, 12, 23, 25, and 40 months respectively. Two patients had nausea or vomiting after each intraventricular injection of Rituximab, but could relieve soon after. Ommaya reservoir infections occured in two patients, and cultures of the cerebrospinal fluid showed MRSCoN and MSSCoN, respectively. They were treated with vancomycin intravenously and via the reservoir. The infections were controlled quickly and their Ommaya reservoirs were kept. One 82 years old patient developed mild ulceration of the month and anus after treatment with regimen A. Hematological toxicities were mild, and could recover quickly with no need of transfusion or the use of G-CSF. In summary, the treatment of Intraventricular Rituximab via Ommaya reservoir combined with systemic chemotherapy for patients with PCNSL was safe and effective. This remedy is likely to improve the prognosis of such patients, but more cases need to be studied for the long-term result.