ALBERT

Description: Introduction: Denosumab is a monoclonal antibody targeting receptor activator of nuclear factor-kappa B ligand (RANKL) that has been shown to reduce skeletal-related events (SREs) associated with bone lesions in patients with multiple myeloma. Results from the full primary analysis of an international, double-blind, double-dummy, randomized controlled phase 3 (20090482) study that assessed the efficacy and safety of denosumab vs zoledronic acid for preventing SREs in patients with multiple myeloma (MM) indicated that denosumab was non-inferior to zoledronic acid for time to SREs. Here we present a sub-analysis to evaluate efficacy and safety outcomes in a subgroup of Asian patients enrolled in the 20090482 study. Methods: Adult patients from Asian countries with newly diagnosed MM and ≥1 documented lytic bone lesion were included in this analysis. Patients received subcutaneous denosumab (120 mg) plus intravenous placebo or intravenous zoledronic acid (4 mg) plus subcutaneous placebo in 4-week cycles. The primary endpoint was time to first on-study SRE; the incidence of adverse events (AEs) by preferred term was also examined. Results: Overall, 196 Asian patients (denosumab, n=103; zoledronic acid, n=93) were included in this analysis. Patient demographics were generally well balanced between groups. Median (interquartile range [IQR]) number of months on study was 17.5 (9.8-30.2) for the denosumab group and 20.2 (13.1-29.2) for the zoledronic acid group. Median (IQR) cumulative drug exposure was 15.9 (8.5-24.0) months for denosumab and 17.4 (9.1-26.7) months for zoledronic acid. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% in the denosumab group and 50.5% in the zoledronic acid group. Median (95% CI) time in months to first on-study SRE was not reached (11.2-not reached) for the denosumab group and 12.3 (3.1-not reached) for the zoledronic acid group (hazard ratio [HR], 0.77; 95% CI, 0.48-1.26; Figure 1). Overall, all patients (100%) experienced ≥1 treatment-emergent AE; the AEs reported in ≥20% of patients in either treatment arm are presented in Table 1. The most common AEs reported in either subgroup (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), pyrexia (38.2%, 41.3%), upper respiratory tract infection (37.3%, 40.2%), and constipation (33.3%, 31.5%). Renal toxicity (preferred terms of blood creatinine increased, renal failure, urine output decreased, acute kidney injury, renal impairment, and blood urea decreased) occurred in 9 of 102 (8.8%) patients in the denosumab group and 20 of 92 (21.7%) patients in the zoledronic acid group. Adjudicated osteonecrosis of the jaw was reported in 7 (6.9%) patients in the denosumab group and 5 (5.4%) patients in the zoledronic acid group. Hypocalcemia was reported in 19 (18.6%) patients in the denosumab group and 17 (18.5%) patients in the zoledronic acid group. Conclusion: Results from this Asian subgroup analysis were comparable to those of the full analysis set. In addition, in this analysis there were numerically fewer patients in the denosumab arm that developed a first on-study SRE compared with those in the zoledronic acid arm, and the time to first on-study SRE had a trend favoring the denosumab-treated patients. The AE profiles for denosumab and zoledronic acid in the Asian subgroup were comparable to those observed in the full primary analysis, with renal toxicity similarly reported to be higher in the zoledronic acid group. Overall, this analysis supports that denosumab may be an additional treatment option for the standard of care for Asian patients with newly diagnosed MM with bone disease. Disclosures Chng: Merck: Research Funding; Aslan: Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Amgen: Consultancy, Honoraria, Other: Travel, accommodation, expenses. Chang:BMS: Consultancy, Speakers Bureau; AbbVie: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy; Takeda: Consultancy; Roche: Consultancy, Speakers Bureau; Novarits: Consultancy, Speakers Bureau. Wong:Amgen: Consultancy, Research Funding, Speakers Bureau; Bayer: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Archigen: Research Funding; Baxalta: Research Funding; Pfizer: Research Funding; Apellis: Research Funding; Roche: Research Funding; Boehringer: Research Funding; Ingelheim: Research Funding; AbbVie: Research Funding; Alexion: Consultancy; Astellas: Speakers Bureau. Shimizu:Amgen Inc.: Other: Non-remunerative Position of Influence, Denosumab 20090482 Global Steering Committee Member; Fujimoto Pharmacuetical Corp: Consultancy; Daiichi-Sankyo, Co., Ltd: Consultancy. Gao:Amgen Asia Holding Limited: Employment, Equity Ownership. Glennane:Amgen: Employment, Equity Ownership. Guan:Amgen: Employment, Equity Ownership.

Description: Introduction: Denosumab is a monoclonal antibody targeting Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL) that has been shown to reduce skeletal related events associated with bone lesions in patients with multiple myeloma and solid tumors. Results from the full primary analysis of 1718 patients with newly diagnosed multiple myeloma in an international double blind, randomized, controlled phase 3 (20090482) study that assessed the efficacy of denosumab (Dmab) vs zoledronic acid (ZA) for preventing SREs met its primary end point of non-inferiority regarding time to first SRE. The analysis of the PFS exploratory endpoint showed a clinically meaningful 10.7 months median PFS benefit (HR, 0.82; 95% CI, 0.68-0.99; descriptive P= 0.036) of Dmab vs ZA. This benefit was most pronounced in patients who were stratified into the "intent to undergo Autologous Stem Cell Transplant (ASCT)" group at randomization. Thus, we present an in-depth analysis of relevant baseline characteristics, treatment regimens and PFS outcome in patients with intent to undergo transplant receiving Dmab and ZA. Methods: Adult patients with newly diagnosed multiple myeloma (NDMM) and stratified as "intent to undergo ASCT" at randomization were included in this analysis. Patients received subcutaneous denosumab (120 mg) plus intravenous placebo or intravenous zoledronic acid (4 mg) plus subcutaneous placebo in 4-week cycles. In this subgroup, the PFS outcome was examined. Baseline characteristics and treatment regimens were compared between treatment arms. Results: 54.1% of the 1718 enrolled patients were stratified into "intent to undergo ASCT" as part of their front-line therapy, and 61.8% of "intent to undergo ASCT" did receive an ASCT. In the "intent to undergo ASCT" group, 19.6% patients had disease progression in the Dmab arm compared to 28.0% in the ZA arm (HR 0.65 (0.49-0.85)) (Figure 1). No imbalance in terms of triplet therapy use between the two study arms (TABLE 1). 55.1% in Dmab vs 52.6% in ZA arm received Triplet Therapies which included Bortezomib, Cyclophosphamide, Dexamethasone (VCD), Bortezomib, Thalidomide, Dexamethasone (VTD), Cyclophosphamide, Thalidomide, Dexamethasone (CTD), or Bortezomib, Lenalidomide, Dexamethasone (VRD). The percentage of triplet therapies used in the "intent to undergo ASCT"patients was higher than in patients with no intent to undergo ASCT. Percentage of patients with ECOG performance status 2 was 19.4% in the Dmab group vs 18.6% in the ZA group. 26.2% of patients in the Dmab arm and 25% in the ZA arm had Multiple Myeloma ISS stage III upon diagnosis. Among intent to transplant patients there was no imbalance in terms of age, performance status, ISS stage, risk status, weight, bone marrow plasma cell % between the ZA and the Dmab arm Conclusion: Results from this post-hoc subgroup analysis suggest a more profound PFS benefit in the "intent to undergo ASCT" patient subgroup. Multiple myeloma treatment received in the intent to undergo transplant subjects was similar between the denosumab and zoledronic acid arms. No significant imbalance in demographics or baseline disease characteristics was observed between the two treatment arms. Disclosures Terpos: Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria; Genesis: Honoraria, Other: Travel expenses, Research Funding; Celgene: Honoraria. Shimizu:Medical Biological Laboratory: Consultancy; Takeda: Speakers Bureau; Daiichi: Consultancy; Amgen: Consultancy; Fujimoto: Consultancy. Willenbacher:Abbvie: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; oncotyrol: Employment, Research Funding; Gilead Science: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; European Commission: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tirol Program: Research Funding; Fujimoto: Consultancy, Honoraria; Myelom- und Lymphomselbsthilfe Österreich: Consultancy, Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; IQVIA: Membership on an entity's Board of Directors or advisory committees. Glennane:amgen: Employment, Equity Ownership. Dai:Amgen: Employment, Equity Ownership. Pasteiner:Amgen: Employment, Equity Ownership. Raje:Amgen Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy.

Description: We analyzed the presenting features and survival in 1689 patients with multiple myeloma aged younger than 50 years compared with 8860 patients 50 years of age and older. Of the total 10 549 patients, 7765 received conventional therapy and 2784 received high-dose therapy. Young patients were more frequently male, had more favorable features such as low International Staging System (ISS) and Durie-Salmon stage as well as less frequently adverse prognostic factors including high C-reactive protein (CRP), low hemoglobin, increased serum creatinine, and poor performance status. Survival was significantly longer in young patients (median, 5.2 years vs 3.7 years; P 〈 .001) both after conventional (median, 4.5 years vs 3.3 years; P 〈 .001) or high-dose therapy (median, 7.5 years vs 5.7 years; P = .04). The 10-year survival rate was 19% after conventional therapy and 43% after high-dose therapy in young patients, and 8% and 29%, respectively, in older patients. Multivariate analysis revealed age as an independent risk factor during conventional therapy, but not after autologous transplantation. A total of 5 of the 10 independent risk factors identified for conventional therapy were also relevant for autologous transplantation. After adjusting for normal mortality, lower ISS stage and other favorable prognostic features seem to account for the significantly longer survival of young patients with multiple myeloma with age remaining a risk factor during conventional therapy.

Description: Background In Japan, the phase II study of bortezomib-melphalan-prednisolone (VMP) for NDMM using the same protocol of VISTA trial revealed that there were more treatment discontinuation in this study than in the VISTA study. We planned five cycles of reduced intensity VMP therapy as an induction. And it is reported that lenalidomide plus low dose dexamethasone (Rd) therapy is very effective regimen after VMP therapy. In order to further improve its outcome, patients are treated with six cycles of Rd and maintenance of lenalidomide after VMP induction. Patients and methods We included 82 pts with NDMM. Pts were received 5 cycles of VMP followed by 6 cycles of Rd. After Rd, pts received maintenance of lenalidomide. VMP included the IV or SQ administration of weekly bortezomib at 1.3 mg/m2 in combination with oral melphalan 6 mg/m2 and prednisone 60 mg/m2 once daily on days 1-4 of a 35-day cycle. Rd treatment consisted of lenalidomide 25 mg daily on days 1-21 plus dexamethasone 40 mg weekly of a 28-day cycle. Lenalidomide maintenance therapy consisted of lenalidomide 10 mg daily on days 1-21 of a 28-day cycle. Results In total, 82 pts were recruited in the trial by 27 Japanese centers between 10/2012 and 8/2014. Median age were 73.5 years (range 61-84), 37.8% were 75 years of age or older, 45.1% were male, 48.8% had International Staging System (ISS) stage II and 20.7% had ISS stage III. Fifty four patients had IgG-type myeloma (65.8%), 19 had IgA-type (23.2%), and 9 had Bence Jones-type (11%). Of the cases analyzed by FISH (N=80), 16.3% had t(4;14), 10% had del 17p and 41.3% had +1q21. Eight patients (10%) had t(4;14) and +1q21, five patients (6.3%) had del 17p and +1q21 and only one patient (1.3%) had t(4;14), del 17p and +1q21. The best response during VMP therapy (the maximum treatment number was 5 cycles) could be evaluated. After five course of VMP therapy, the rates of partial response (PR) or better were 68% including sCR (5%), CR (6%),VGPR (20%) and PR (37%). The best response rate after VMP+Rd (maximum treatment number of Rd was 6 cycles) was also evaluated. The rates of PR or better were 90% including sCR (6%), CR (16%), VGPR (39%) and PR (29%). The most commonly observed grade 3 or higher adverse events during VMP therapy were anemia (30%), neutropenia (16%), thrombocytopenia (5%) and GI toxicity (6%). Summary The induction therapy of reduced intensity VMP was safe and effective. The best response rate after VMP+Rd was very effective. However, we need to evaluate consolidation of Rd and maintenance of lenalidomide after longer follow up. Disclosures Ishida: Takeda: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Honoraria. Sunami:Ono: Research Funding; Takeda: Research Funding.

Description: Introduction A significant progress in the management of multiple myeloma (MM) has been made in recent years by the introduction of novel treatment modalities including high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) and novel drugs such as proteasome inhibitors and immunomodulatory drugs (IMiDs). Nevertheless, MM is still an incurable disease with various complications, and it is not clear whether these approaches contribute to the improvement of patient outcomes in routine practice. Previously, the Japanese Society of Myeloma surveyed the clinical features of 1383 patients with MM diagnosed and treated between January 1990 and December 2000. In the present study, we conducted a multicenter retrospective study to evaluate the treatment outcome and prognostic factors in the era of novel agents in Japan involving 2593 new patients diagnosed and treated after December 2000. Patients and Methods We analyzed 2593 patients with symptomatic MM newly diagnosed in the period between January 2001 and December 2012 at the affiliated hospitals of the Japanese Society of Myeloma. This study was conducted in accordance with the institutional guidelines with approval of the local institutional review board. There were 1342 males and 1251 females. The median age was 66 (range 26-96) years; 21% were older than 75 years. The type of monoclonal immunoglobulin was IgG in 1547 patients, IgA in 488, light chain only in 399, IgD in 72, and others in 87, respectively. Performance status (PS) of 0, 1, ≥2, and unknown were 340, 657, 756, and 840 patients, respectively. Durie & Salmon stage was as follows: 8.4% had Stage I, 25.5% Stage II, and 66.1% Stage III, respectively. As for the International Staging System (ISS) stages, 28.0% had stage I, 38.0% stage II, and 34.0% stage III, respectively. Cytogenetic abnormalities were detected in 24.9% of the patients. Initial therapy was composed of conventional chemotherapy in 45.6%, novel agents such as bortezomib-based or IMiDs-based regimens in 20.6%, conventional chemotherapy + ASCT in 20.4%, and novel agents (mainly bortezomib) + ASCT in 12.8% of the patients, respectively. Results The median overall survival (OS) was 63.8 and 62.5 months in the 2001-2005 cohort and in the 2006-2012 cohort, respectively, which was significantly improved compared with our previous results of 38.9 months in the 1990-2000 cohort. The median OS tended to be shorter according to the patient age (97.3, 79.7, 56.9, and 44.6 months in the patients aged

Description: Purpose: Deep vein thrombosis (DVT) is increasingly recognized as a major complication of thalidomide (T; Thal) and lenalidomide (R; Rev) based therapy for multiple myeloma. Estimated incidence varies widely in the literature. There is no consensus on specific risk factors, indications for thromboprophylaxis or the agent of choice for DVT prophylaxis. The purpose of this study was to develop a consensus among members of the IMWG. Patients and Methods: A survey was electronically mailed to 67 IMWG members on July 21, 2006 and consisted of 24 multiple-choice questions. Results: Twenty-three IMWG members (34%) sent in their responses by the cut-off date. All (100%) felt that DVT was an important question, but most (95%) did not avoid Thal/Rev based therapy because of the DVT risk. Overall results are summarized in the Table below. A majority of physicians felt that concomitant therapy with high dose dexamethasone (90% of physicians), alkylators (55%), doxorubicin/liposomal doxorubicin (90%), and erythropoietin (75%) increase the risk of DVT associated with Thal or Rev based therapy. Aspirin (81 mg or 325 mg per day) was the preferred choice of prophylaxis when necessary. However, 65% of respondents preferred warfarin to a therapeutic INR or LMW heparin if either doxorubicin or liposomal doxorubicin was added to the regimens. Most (95–100%) felt that DVT prophylaxis was not indicated for: VAD, MP, bortezomib +/− dexamethasone regimens. Seventy-five percent felt it to be safe to resume therapy with Thal/Rev after therapeutic anticoagulation. Most (95%) believed randomized trials were needed. Conclusion: DVT is recognized as a major clinical problem associated with Thal/Rev containing regimens. Most respondents felt that the DVT risk did not warrant any prophylaxis when either Thal or Rev were used as single agents. Aspirin was the preferred form of DVT prophylaxis for most Thal/Rev containing regimens, except when doxorubicin/liposomal doxorubicin or melphalan were added. Additional responses will be analyzed both electronically and by conference call prior to the meeting. Therapy Estimated incidence of DVT (% respondents) Choice of thromboprophylaxis (% respondents) Single agent thal

Description: [Introduction] Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia with poor outcomes. Because of the rarity of the disease, most clinical data have been derived from case reports and small retrospective studies. And accordingly, there has been a limited information about the possible role of novel agents in the treatment of PCL. [Purpose] The objective of this study was to investigate the current treatment status and outcome of Japanese patients with primary PCL (pPCL) in the era of novel agent and to analyze risk factors affecting survival in order to propose an optimal treatment strategy for pPCL in the future. [Patients and Methods] This study was approved by the local institutional review board. Between January 2001 and December 2012, 38 consecutive pPCL patients were treated at the participating hospitals of the Japanese Society of Myeloma among 3318 patients with symptomatic multiple myeloma (MM). Diagnosis was made according to the criteria of International Myeloma Working Group. We investigated clinical characteristics at diagnosis, including age, gender, PS (ECOG), serum biochemistry and hematological parameters, Ig subtypes, the proportion of plasma cells in the bone marrow (BM), cytogenetics including FISH, and clinical stages [Durie & Salmon (DS) staging and International Staging System (ISS)]. The data about treatment regimen, including the first-line and salvage therapy, response rates with first-line therapy and overall survival (OS) were also analyzed. [Results] The incidence of pPCL was 1.1% among patients with symptomatic MM. The median age and male/female ratio were 64 years (range 35-89) and 1.24 (21/17), respectively. The median OS of all pPCL patients was 2.85 years, which was much longer compared with that in the previous reports from USA and Europe. Proportion of patients treated with novel agents during the entire study period was 61% (23/38). OS of the patients treated with novel agents during the period was significantly extended than that of patients treated without novel agents by generalized Wilcoxon test (2.85 years vs 1.16 years, p=0.049); however, there was no significant difference by log-rank test (p=0.28). This finding would implicate that treatment with novel agents could have prevented early death in patients with pPCL. There was no significant difference in OS between patients who received autologous stem cell transplantation (ASCT) and who did not (2.85 years vs 2.34 years). Only age was statistically significant prognostic factor for inferior OS (HR, 4.57). Patients older than 65 years tended to have received treatment without novel agents (47% vs 74%), so the lack of novel therapy might have contributed to the inferior survival of the elderly patients. Five patients received maintenance therapy with novel agents, and OS of these patients tend to be longer than that of the other patients (4.45 years vs 2.85 years). [Conclusion] The incidence of pPCL in Japan was similar to that in USA and Europe; however the OS of Japanese patients was significantly better than that reported from USA and Europe. This might result from the maintenance therapy with novel agents used in Japanese patients. Unlike MM, OS with pPCL has not been improved significantly in the last decade, especially in the elderly patient population, it would be important to establish the treatment strategy, particularly after induction treatment, such as intensification/maintenance therapy. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 5035 Background: The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However the difference of clinical characteristics between ethnic groups is not well-defined. In Asian countries the incidence of MM has been lower compared with Western countries. However, there are growing evidences that MM is increasing very rapidly in this region. Until now, only few data of Asian patients has been reported. Asian myeloma network (AMN) decided to analyze the first multinational project to explore clinical characteristics of Asian MM patients and clinical practice performed in Asian countries. Methods: Data were collected from 22 centers from 7 countries and regions were collected retrospectively. Clinical characteristics of 3377 symptomatic MM patients at diagnosis were described. Overall survival (OS) and prognostic factors were analyzed for 3324 patients who have survival data. Results: Clinical and genetic characteristics were summarized at table 1. Median OS was 47 months (95% CI 48. 0–60. 0). Patients who were diagnosed before 2000 were shorter survival. Transplantation was performed to 607 patients with better survival (84 vs 40 months, p

Description: Introduction: The full primary analysis of the international, double-blind, double-dummy, randomized controlled phase 3 study (20090482) that assessed the efficacy and safety of denosumab vs zoledronic acid for preventing skeletal-related events (SREs) in newly diagnosed patients with multiple myeloma (NDMM) met the primary noninferiority endpoint of time to first on-study SRE (Raje N, et al. Lancet Oncol. 2018). Overall survival, a secondary endpoint, was similar in both arms; however, this result was based on a limited number of events having occurred (denosumab 14.1% vs zoledronic acid 15.0%), which might have affected the ability to detect a difference and also may have been further diluted by multiple subsequent lines of therapy. In addition, results from an exploratory endpoint, progression-free survival (PFS), demonstrated a clinically meaningful 10.7 months median PFS benefit (hazard ratio [HR], 0.82; 95% CI, 0.68-0.99; descriptive P=0.036; Table 1) of denosumab versus zoledronic acid on top of standard of care first-line anti-myeloma treatment. This result provided suggestive clinical evidence of a potential anti-myeloma effect based on RANKL inhibition. Here we present further analysis of PFS according to prespecified subgroups of patients from the 20090482 study. Methods: Adult NDMM patients with ≥1 documented lytic bone lesion were included in this study. Patients received subcutaneous denosumab (120 mg) plus intravenous placebo or intravenous zoledronic acid (4 mg) plus subcutaneous placebo every 4 weeks. Both groups also received investigators' choice of first-line anti-myeloma therapy. The exploratory endpoint PFS (time from randomization to date of first overall disease progression or death due to any cause, investigator identified) was estimated using the Kaplan-Meier method and analyzed using a Cox proportional hazards model stratified by randomization stratification factors and adjusted for baseline covariates. PFS subgroup analyses were conducted according to the novel first-line therapy use (proteasome inhibitor [PI] use, immunomodulatory drug [IMiD] use, PI and IMiD use) and the intent to receive an autologous stem cell transplant (ASCT; yes, no). Results: Overall, 1718 patients (denosumab, n=859; zoledronic acid, n=859) were included in the primary analysis. By the time of the primary analysis cut-off, 219 patients (25.5%) in the denosumab group and 260 patients (30.3%) in the zoledronic acid group had a PFS event. The percentages of patients receiving novel first-line therapy were balanced between the two groups (see Table 1). For patients who had received first-line PI-based therapy, PFS favored denosumab vs zoledronic acid (median, 40.0 vs 35.4 months; HR, 0.74; 95% CI, 0.58-0.95; descriptive P=0.019; Table 1). For patients who had received first-line IMiD only-based therapy, median PFS was not reached with denosumab therapy and was 34.3 months with zoledronic acid therapy (HR, 0.85; 95% CI, 0.53-1.35; descriptive P=0.49). Median PFS was also not reached for either denosumab or zoledronic acid for patients who had received first-line PI plus IMiD therapy (HR, 0.95; 95% CI, 0.62-1.46; descriptive P=0.82). For patients with the intent at baseline to receive an ASCT (54% in each treatment group; Table 1), PFS favored denosumab vs zoledronic acid (median, 46.1 vs 35.7 months; HR, 0.65; 95% CI, 0.49-0.85; descriptive P=0.002). Conclusion: Overall results from this subanalysis indicated PFS impact and benefit of denosumab on top of anti-myeloma therapy, independent from first-line novel therapy which was balanced among treatment arms, mainly in the subgroup of patients receiving PI only-based first-line therapy. In addition, benefit was observed in patients with the intent to receive ASCT, described with an impressive HR of 0.65. Disclosures Terpos: Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; BMS: Consultancy; Novartis: Consultancy. Willenbacher:Amgen: Honoraria, Other: Steering board, Research Funding; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Roche: Honoraria, Research Funding; BMS: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Merck: Honoraria. Shimizu:Daiichi-Sankyo, Co., Ltd: Consultancy; Fujimoto Pharmacuetical Corp: Consultancy; Amgen Inc.: Other: Non-remunerative Position of Influence, Denosumab 20090482 Global Steering Committee Member. García-Sanz:Hospira: Research Funding; Pharmacyclics: Research Funding; Spanish Government: Research Funding; Gilead: Research Funding; Amgen Inc.: Research Funding; Incyte: Consultancy; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Glennane:Amgen: Employment, Equity Ownership. Guan:Amgen: Employment, Equity Ownership. Niepel:Amgen Inc.: Employment, Equity Ownership. Raje:BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Merck: Consultancy; Takeda: Consultancy; AstraZeneca: Research Funding; Research to Practice: Honoraria; Medscape: Honoraria; Amgen Inc.: Consultancy.

Description: Introduction: Survival outcome of patients with multiple myeloma (MM) is heterogeneous because of different disease- and patient-related prognostic factors as well as in treatment-related factors. A survival benefit of continuous and maintenance (C/M) therapies after induction therapy in both transplant-eligible and -ineligible patients has been demonstrated in clinical trials. However, its usefulness is still to be clarified in the patients treated in routine clinical practice. Here, we report survival outcome of patients who received C/M therapy after induction therapy by analyzing the data of a multicenter retrospective study of the Japanese Society of Myeloma. Methods: Compiled clinical data of the patients diagnosed with MM and treated between 2013 and 2016 were analyzed retrospectively. Treatment decision whether or not to implement autologous stem cell transplantation (ASCT) was made at the discretion of a physician-in-charge. Treatment response was assessed by the investigators according to the International Myeloma Working Group uniform response criteria. Treatment decision to implement maintenance therapy after ASCT or to continue frontline treatment in non-transplanted patients was made based on the response to frontline treatment by the physician-in-charge. Patients were bifurcated using the propensity score methods in terms of age, gender, R-ISS stage, and commencement of ASCT to those who received C/M therapy and others without. Results: A total of 771 patients were enrolled. Among them, 216 patients received frontline C/M therapy, while the remaining 555 patients did not. In 720 patients who have achieved at least stable disease after induction therapy with or without ASCT, 161 patients of C/M group and another 161 patients of non-C/M group were matched according to the baseline covariates. Patient demographics and disease characteristics were well balanced between the matched set of patients (C/M vs non-C/M) in terms of median age (years, 65 vs 65), gender (male, 52% vs 53%), and R-ISS (stage I, 19% vs 20%; stage II, 70% vs 69%; and stage III, 11% vs 11%), respectively. ASCT were performed in 54% vs 54% in either group. C/M regimens included lenalidomide (n=73), bortezomib (n=35), ixazomib (n=9), elotuzumab (n=6), thalidomide (n=5), carfilzomib (n=2), combination of proteasome inhibitors and IMiDs (n=28), and others (n=3). Median PFS was significantly prolonged in the C/M group compared with the non-C/M group (37.7 vs 21.6 months, p=0.00017, Figure A). Median PFS in each of the two groups of the transplanted and non-transplanted patients were 40.5 vs 29.5 months (p=0.0063) and 24.6 vs 11.2 months (p=0.0013), respectively. For patients who have attained a CR after the frontline therapy, there was no significant difference in median PFS between the C/M and non-C/M groups (not reached vs 37.5 months, p=0.39). However, there was a significant prolongation of median PFS in the C/M group among those who did not achieve a CR (33.0 vs 19.2 months, p=0.006). Median OS was not reached in either groups, but it appeared to be longer in the C/M group than in the non-C/M group (p=0.061, Figure B). Although median OS of both groups were similar in the transplanted patients (p=0.56), there was a significant prolongation in the non-transplanted patients (58.1 months vs not reached, p=0.024). For those who have attained a CR, there was no significant difference in median OS between the C/M and non-C/M groups (p=0.29), but for those who did not achieve a CR, there was a significant prolongation of median OS in the C/M group (58.1 months vs not reached, p=0.048). A significant beneficial impact of C/M therapy on PFS and OS was observed in the R-ISS stage II and III patients but not in the stage I patients. In multivariate analysis, R-ISS stage, CR response after frontline therapy, ASCT, and C/M therapy were significant prognostic factors for PFS, whereas R-ISS and C/M therapy were associated with prolonged OS. Conclusions: C/M therapy had a beneficial impact on PFS and OS especially in patients with non-transplanted, non-CR response, and R-ISS stage II and III cohorts, but exerted less impact on standard-risk patients in our current clinical practice. Thus, C/M therapy is a key strategy for high-risk patients, but clarification of patients other than risk status who benefit from C/M therapy might be needed to further improve the prognosis of high-risk patients with MM. Disclosures Handa: Ono: Research Funding. Sunami:MSD: Research Funding; GSK: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Alexion-pharma: Research Funding; Janssen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Research Funding; Daiichi Sankyo: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Suzuki:Ono: Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Iida:Takeda: Honoraria, Research Funding; Sanofi: Research Funding; Gilead: Research Funding; Celgene: Honoraria, Research Funding; Daichi Sankyo: Honoraria, Research Funding; Kyowa Kirin: Research Funding; Abbvie: Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; MSD: Research Funding; Chugai: Research Funding; Janssen: Honoraria, Research Funding; Astellas: Research Funding; Teijin Pharma: Research Funding. Nishimura:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy; Celgene K.K.: Honoraria. Shimizu:Amgen: Consultancy; Fujimoto: Consultancy; Daiichi: Consultancy; Medical Biological Laboratory: Consultancy; Takeda: Speakers Bureau.