ALBERT

Description: Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant plasma cell disorder. Previous studies in Western countries have described the prevalence of MGUS in Caucasians. However, data is limited in Chinese population. We therefore performed this study to ascertain the prevalence and characteristics of MGUS among Chinese population. Methods A total of 154597 consecutive healthy participants from Beijing who underwent annual physical examination between December 2013 and April 2019 at Peking Union Medical College Hospital were enrolled. Serum M protein was evaluated by capillary electrophoresis. Patients with a positive or suspicious serum M protein were suggested to be referred to the hematological clinic for immunofixation electrophoresis (IFE) and free light chain (FLC) assays. MGUS was defined in accordance with previous definitions. We calculated age-specific and sex-specific prevalence and described laboratory characteristics of patients with MGUS among those participants. Results MGUS were diagnosed in 843 patients (0.55%, 95%CI 0.51% to 0.59%). The median age at presentation was 58 years, with a range of 25-96 years. The overall prevalence of MGUS was 1.14% among participants aged 50 years or older and 2.6% among those aged 70 years or older. In both sexes, the prevalence increased with age: 0.1% (

Description: POEMS syndrome is a rare clonal plasma cell disorder without standard treatment. Based on the efficacy and low toxicity of a combination of melphalan and dexamethasone (MDex) for light chain amyloidosis, we conducted a prospective study of MDex treatment for patients with newly diagnosed POEMS syndrome. Thirty-one patients (19 men) were enrolled and the median age at the time of diagnosis was 44 years (range, 32-68 years). All patients received 12 cycles of MDex treatment. Twenty-five patients (80.6%) achieved hematologic response including 12 (38.7%) complete remission and 13 (41.9%) partial remission. Of all 31 patients, the neurologic response rate was 100%, assessed by overall neuropathy limitation scale (ONLS). The initial neurologic response was observed in 24 patients (77.4%) at 3 months after treatment and the median time to maximal neurologic response was 12 months (range, 3-15 months). Moreover, MDex substantially improved the level of serum vascular endothelial growth factor and relieved organomegaly, extravascular volume overload, and pulmonary hypertension. Only 6 patients (19.3%) suffered from grade 3 adverse events during treatment. All patients are alive and free of neurologic relapse after the median follow-up time of 21 months. Therefore, MDex is an effective and well-tolerated treatment option for patients with newly diagnosed POEMS syndrome.

Description: Background The combination of lenalidomide (LEN) and low-dose dexamethasone (LoDEX) is approved in China for the treatment of multiple myeloma (MM) patients (pts) who have received at least 1 prior antimyeloma treatment. The MM-021 China registration study demonstrated the efficacy and safety of LEN + LoDEX (Rd). This sub-analysis investigated the impact of the number of prior antimyeloma therapies on treatment outcomes. Methods MM-021 was a phase 2, multicenter, single-arm, open-label study. Relapsed and refractory MM (RRMM) pts (aged ≥ 18 yrs) were given LEN (25 mg/day on days 1-21) and LoDEX (40 mg/day on days 1, 8, 15, and 22) in 28-day treatment cycles until disease progression or discontinuation. Pts included in the pharmacokinetics cohort did not receive DEX on day 1, cycle 1. All pts received thromboprophylaxis during the study. The primary end-point was best overall response rate (ORR), defined as the percentage of pts who achieved a best response of at least partial response. Secondary end-points included progression-free survival (PFS), time to progression (TTP), overall survival (OS), and safety. Data were analyzed according to the number of therapies that pts had received prior to study screening: 1-2, 3-4, or 〉 4. Results The analysis cut-off date was January 4, 2013, with a median follow-up of 17.6 mos. All pts in the intent-to-treat (ITT) population (N = 199) were included in the safety analysis, and 187 pts were included in the efficacy-evaluable (EE) population. At the cut-off date, 42 pts had completed treatment and 157 had discontinued. Overall, the median age of pts was 59.0 yrs (range 35-81) and 62.8% were male. The majority of pts had advanced disease (85.9% had Durie-Salmon stage III MM); 40.7% of pts (ITT population) had received 〉 4 prior anti-myeloma therapies; 33.2% had received 3-4, and 26.1% had received 1-2. Most pts had received prior treatment with thalidomide (THAL; 68.8%) or bortezomib (BORT; 63.8%) (Table 1). After a median treatment duration of 8.3 mos (range 0.9-24.8) or 9 treatment cycles (range 1-27), the ORR was 47.6% in the overall EE population, and highest in pts who had received 1-2 prior therapies (Table 2). Median OS, PFS, and TTP were longer in pts who had received 1-2 prior therapies compared with those who had received 3-4 and 〉 4 prior therapies, and compared with the overall EE population (Table 2). In the safety population, the most common grade 3-4 treatment-emergent adverse events (TEAEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). In general, grade 3-4 TEAE rates were lower in pts who had received 1-2 prior therapies (60%), and comparable in pts who had received 3-4 (71%), 〉 4 prior therapies (75%), and the overall safety population (70%). There were 2 reports of grade 3-4 peripheral neuropathy. AEs resulted in discontinuation of LEN in 5.8% (n = 3), 10.6% (n = 7) and 9.9% (n = 8), of pts who had received 1-2, 3-4 and 〉 4 prior therapies, respectively. Conclusion Rd is an effective treatment option for Chinese RRMM pts who have relapsed after one or more prior therapies, including THAL and/or BORT. More robust efficacy and higher ORR was observed for Rd in patients who had received 1-2 prior therapies compared to those who had received additional lines of treatment. The tolerability of Rd was similar in heavily and less heavily pretreated pts. Discontinuations were infrequent, even in heavily pretreated pts who had received 〉 4 prior therapies. Disclosures: Zhang: Celgene Corporation: Employment, Equity Ownership. Wortman-Vayn:Celgene Corporation: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. 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; J & J: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti–interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated a thalidomide-cyclophosphamide-prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P 〈 .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105.

Description: 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.

Description: Objectives: Erdheim-Chester disease (ECD) is a rare multi-systemic form of histiocytosis. Treatment with BRAF inhibitors has markedly improved outcomes for patients with ECD; however, the estimated annual cost of BRAF inhibitors is approximately $50,000 in China. Interferon-α (IFN-α)has been used with variable efficacy as a treatment for ECD. The estimated annual cost of IFN-α is approximately $1600 in China. The aim of the current study was to describe the long-term treatment outcomes and efficacy of FDG-PET for evaluating therapeutic responses among a cohort of ECD patients who were treated with IFN-α. Methods: We retrospectively evaluated newly diagnosed ECD patients who received 600 MIU or 900 MIU of IFN-α, three times/week subcutaneous for at least 1 month at Peking Union Medical College Hospitalbetween January 2010 and May 2018. All patients were followed up every 3-6 months. We defined the most active lesion measured by standardized uptake value (SUV) on FDG-PET before treatment as target lesions. We used the ratios between most active target lesion SUV and liver SUV (SUVmax/SUVliver) for follow-up, to eliminate heterogeneity. Results: A total of 32 patients (16 male and 16 female) met the inclusion criteria. Four of them were diagnosed with mixed ECD and Langerhans cell histiocytosis. The median age at diagnosis was 48 years (range, 6-66 years). The median number of involved organs was four (range 1-8). The main sites of involvement were the bones (93.8%), retroperitoneum (40.6%), lungs (37.5%), vasculature (37.5%), central nervous system (CNS, 34.4%), pericardium (28.1%), pleura (21.9%), skin (18.8%), pituitarium (15.6%), heart (12.5%), retro-orbital involvement (12.5%), nerve root (9.4%), muscles (6.3%), thymus (6.3%), thyroid (3.1%) and breasts (3.1%). Two patients did not have an adequate amount of tissue available for genomic testing. BRAFV600Emutations were detected among 21/30 patients (70.0%). The most active target lesions at baseline detected by FDG-PET were bone (58.3%), followed by CNS (15.0%), pleura (5.0%), nerve root (5.0%) and muscle (5.0%). In all, 26 patients (81.3%) received IFN-α as the first-line treatment. Four patients (12.5%) received IFN-α after cytarabine based chemotherapy as maintenance therapy. Two patients (6.2%) received IFN-α as second-line therapy. The median duration of IFN-α therapy was 18.5 months (range, 1-51 months). One patient stopped IFN-α treatment because of intolerable adverse effects after 8 months. The overall clinical response rates were 80.0%, including 33.3% complete response, 36.7% partial response, and 10.0% stable disease. Thirty-one patients underwent a total of 81 scans by PET. A total of 17 patients underwent at least one follow-up FDG-PET scan, median of 4 (2-6). The SUVmax / SUVliver changed during treatment (Figure 1). At the last follow-up, nine (52.9%) of these patients had experienced a partial metabolic response. The median reduction in SUVmax / SUVliverfrom baseline to last PET/CT scan was 61.4% (range, 8.8%-86.6%). Thirteen (76.5%) patients experienced continuous clinical improvement during follow-up. Eight of 13 (61.5%) patients recorded at least one SUVmax / SUVliverincrease during follow-up: the median increase in this ratio was 32.0% (range, 2.6%-45.4%), which decreased in subsequent scans without changing the treatment (Figure 2). The estimated 3-year progression-free survival (PFS) and overall survival (OS) were 64.1% and 84.5%, respectively. The univariate analyses of survival showed that a significantly higher PFS was attained in patients without CNS involvement compared to those with CNS involvement (not reached vs 24 m, p=0.018).Patientswithout CNS involvement also had a significantly higher OS than those with CNS involvement (p=0.023). BRAF status was not an independent prognostic factor for PFS or OS. Conclusion: High-dose IFN-α treatment is a cost-effective option, especially for patients without CNS involvement. Single target lesion SUV elevation according to FDG-PET do not accurately demonstrate disease progression, but serial FDG-PET imaging effectively discriminate treatment response. Disclosures No relevant conflicts of interest to declare.

Description: Background:Bortezomib had been used as a standard treatment in plasma cell disorders patients for years. It has been proved that subcutaneous bortezomib was locally well tolerated, had non-inferiority effect andless peripheral neuropathy compared with intravenous administration. Few studies about home treatment of bortezomib had been reported to be feasible and of benefit to patients. But in these studies, bortezomib was adminstrated by special nurse visiting home regularly.In consideration of the shortage of medical resources in China and aiming to make it easier to receive bortezomib treatment for patients, we made a preliminary exploration of home treatment of bortezomib by patients or relatives themselves in China for the first time. Methods:234 patients provided written informed consent were enrolled in our study between March 2018 and April 2019.A clinical nurse specialist provided hands-on guidance on home-injection for patients in outpatient department. The following information including geographical and clinical data, adverse events in treatment, feedback from patients about cost and time saved than hospital injection, and difficulty degree and satisfaction with home treatment using a rating scale between 0 and 10 were collected. The higher the score, the easier the injection and more satisfied with the mode of home treatment. Results:The median age at diagnosis was 56 (27-83) years old. 75 (32.1%) patients were diagnosed with primary light chain amyloidosis, 70 (30.0%) POEMS syndrome, 62 (26.5%) multiple myeloma, 15 (6.4%) multi-center Castleman disease, 4 (1.7%) light chain deposition disease, 4 (1.7%) Waldenstrom's macroglobulinemia, 2 (0.9%) cryoglobulinemia, 1 (0.4%) mycosis fungoides and 1 (0.4%) monoclonal gammopathy-associated scleromyxedema.Patients lived within a 3,010 kilometer radius of the city of Beijing, 46 (19.7%) patients lived in Beijing and 67 (28.6%) patients lived more than 1,000 kilometers from our hospital (Figure 1. Geographical distribution of 234 patients. The dots represent number of patients in different provinces. The blue dot represents 46 patients lived in Beijing, the city our hospital located in). As so far, patients received a median number of 20 (4-36) injections and a total of 5068 injections of bortezomib. The most common injection-site reaction was redness (24.8%) and pigmentation (20.9%). In 5068 injections, 2 (0.04%) local hematomas at injection site, 7 (0.14%) injection dose errors and 5 (0.10%) needlestick injuries occurred, respectively. Medicine bottle was broken during drug dissolution for only once (0.02%). The median cost and time saved was RMB 200 (100-6000) and 4.5 (0.5-100) hours per injection per person for home treatment. The total saving of money was RMB 3927,804, and the total time saved was 15,617.5 hours. For the score of difficulty degree of injection and satisfaction with home treatment, 201 (85.9%) and 208 (88.9%) rated 8 and higher, respectively. Conclusion: Home treatment of bortezomib is feasible, and both cost-effective and time-saving in China, which should be promoted in other medical centers. Figure 1 Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Ixazomib (Ninlaro) is the first orally administered proteasome inhibitor (PI) approved in more than 50 countries worldwide, including China. The TOURMALINE-MM1 study was a large randomized, double-blind, global registration study assessing treatment with either ixazomib or placebo added to lenalidomide and dexamethasone. The China Continuation Study (CCS) was a separate regional expansion of the global study that used the same study design. (Panel A) In the global study, IRd treatment extended progression-free survival (PFS), the primary endpoint, by 35% (HR=0.74) vs Rd. Here we report results of a pooled analysis of data from a subgroup of Asian patients enrolled in these two studies. Demographics and Methods: Asian patients from China (n=6 from the global study; n=115 from the CCS), Singapore (n=6), South Korea (n=6), and 3 non-Asian countries (n=5) were included in this pooled analysis. Overall response rate (ORR) was based on the International Myeloma Working Group criteria. The median OS and PFS were calculated using the Kaplan-Meier method. Comparative analysis of treatment groups used stratified log rank tests and the Cox proportional hazard regression model. Safety assessments were based on treatment-emergent adverse events (TEAEs), changes in laboratory parameters, and 12-lead electrocardiogram results. Results: Data from 138 pts were analyzed (67 IRd; 71 Rd). Baseline characteristics were balanced between the treatment groups; overall median age was 61 (range, 30-80) years, 67% of pts were 〈 65 years; 97% of pts had Eastern Cooperative Oncology Group Performance Scores 0-1; 37% had International Staging System (ISS) stages II/III; and 72% had lytic bone disease. The median number of prior treatments was 2, with 82% exposed to thalidomide of which 61% were thalidomide refractory, 61% were exposed to bortezomib, and 48% exposed to both drugs. The ORR was 57% in the IRd group vs 37% in the Rd group. Median OS was 25.8 mos and 15.8 mos in the IRd and Rd treatment groups, respectively (HR=0.346). (Panel B). OS also was longer with IRd therapy regardless of prior exposure to bortezomib (HR=0.322) or thalidomide (HR=0.317) as well as in pts with thalidomide refractory tumors (HR=0.273). (Panel C). The median PFS was 7.3 mos and 4.6 mos in the IRd and Rd treatment groups, respectively (HR=0.559). Longer PFS was also observed with IRd treatment in pts with prior exposure to bortezomib (HR=0.467) or thalidomide (HR= 0.580) as well as pts with thalidomide refractory tumors (HR= 0.631). The rates of drug-related TEAEs (IRd, 96%; Rd, 97%), serious TEAEs (IRd, 37%; Rd, 34%), Grade 3/4 TEAEs (IRd, 74%; Rd, 73%) and discontinuations due to AEs (IRd, 12%; Rd, 13%) were similar in both treatment groups. Grade 3/4 TEAEs reported in ≥10% of either treatment group were anemia (IRd, 14%; Rd, 31%), lower respiratory infection (IRd, 23%; Rd, 21%), neutrophil count decrease (IRd, 13%; Rd, 16%), platelet count decrease (IRd, 15%; Rd, 13%), neutropenia (IRd, 17%; Rd, 9%), thrombocytopenia (IRd 11%; Rd 6%). There was no increased cardiotoxicity, renal toxicity, hepatoxicity or secondary primary malignancy in the IRd group. Conclusions: Asian pts with RRMM treated with oral IRd showed superior OS and PFS vs those treated with Rd. The benefit was consistent regardless of prior exposure to thalidomide and bortezomib. The addition of ixazomib to Rd was well-tolerated, and no new safety signals were identified. The safety profile of IRd was consistent with the safety findings of the large global study (Moreau P, Masszi T, Grzasko N, et al. for the TOURMALINE-MM1 Study group. N Engl J Med. 2016;374:1621-1634.) Disclosures Jin: College of Medicine, Zhejiang University: Employment; The National Natural Science Foundation of China: Research Funding. Chng:Amgen: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Merck: Research Funding; Aslan: Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses. Goh:Johnson & Johnson: Consultancy, Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Wu:Takeda Pharmaceuticals: Employment. Wang:Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda: Employment. Liu:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Skacel:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment; Department of Hematology, Charles University General Hospital, Prague, Czech Republic: Other: Affiliation. Wan:Takeda Pharmaceuticals International Co.: Employment. Berg:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment.