ALBERT

Description: Introduction : Daratumumab (DARA) is a human, CD38-targeted, IgGκ monoclonal antibody. In the CASTOR study, D-Vd reduced the risk of disease progression or death by 68% and induced higher rates of deeper responses vs Vd in relapsed/refractory (RR) MM pts (Spencer, A. ASH 2017. Abs. 3145). Overall, in phase 3 studies in RRMM and newly diagnosed MM, DARA-based regimens reduced disease progression or death risk by ≥50%, doubled complete response (CR) rates, and tripled minimal residual disease (MRD)-negative rates. While progression-free survival (PFS) benefits of D-Vd vs Vd were observed regardless of the number of prior lines (PLs) of therapy, the benefit was most pronounced in pts receiving 1 PL of therapy. Here, we examine updated (2 y after interim analysis) efficacy and safety of D-Vd vs Vd in CASTOR, with a primary focus on pts with 1 PL of therapy. Method: Pts in CASTOR were randomized to receive 8 cycles (21 d/cycle) of V (1.3 mg/m2, SC) on Days 1, 4, 8, and 11 and dexamethasone (20 mg, PO or IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 with or without DARA (16 mg/kg, IV) given weekly for Cycles 1-3, Q3W for Cycles 4-8, and Q4W thereafter. Cytogenetic risk was evaluated centrally by next generation sequencing; high risk was defined as having t(4;14), t(14;16), and/or del17p abnormalities. MRD was assessed at the time of suspected CR and at 6 and 12 mo following the first treatment dose, and an additional MRD evaluation was required every 12 mo post-CR. MRD was evaluated using clonoSEQ® V2.0 (Adaptive Biotechnologies, Seattle, WA). Sustained MRD negativity was defined as maintenance of MRD negativity at 10-5 for ≥6 or ≥12 mo. Results: At the clinical cutoff date of January 11, 2018, 498 pts were included in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247). Pts received a median of 2 (1-10) PLs of therapy including 235 pts that received 1 PL (D-Vd, n = 122; Vd, n = 113). In the ITT population, 61% received prior ASCT, 66% V, 42% lenalidomide (R), and 32% were refractory to their last PL of therapy. Among 1 PL pts, 60% received prior ASCT, 51% V, 20% R, and 18% were refractory to their last PL of therapy. After a median follow-up of 31.3 mo, PFS was significantly prolonged with D-Vd compared with Vd in the ITT population (median: 16.7 vs 7.1 mo; HR, 0.32; 95% CI, 0.25-0.40, P

Description: Key Points Benefit from panobinostat-dexamethasone-bortezomib was greatest in patients who received ≥2 prior regimens including bortezomib and IMiDs.

Description: Background Ixazomib (ixa), the first oral proteasome inhibitor, is approved in combination with lenalidomide (len)-dexamethasone in 〉50 countries globally, including the US and EU, for the treatment of relapsed/refractory MM (RRMM) pts who have received ≥1 prior therapy. Outcomes and tolerability in routine clinical practice often differ from data reported in clinical trials for novel-agent-based MM therapies; however, data directly comparing efficacy in clinical trials with effectiveness in routine clinical practice of new MM agents and regimens are currently limited. To evaluate the effectiveness of IRd in RRMM pts in routine clinical practice, we performed a pooled analysis of individual pt-level data for IRd-treated RRMM pts from the ongoing INSIGHT MM (NCT02761187) study and from the Czech RMG. INSIGHT MM is the largest global, prospective, observational MM study conducted to date, which is currently enrolling ~4200 adult pts with newly diagnosed MM or RRMM from Europe (EUR), the US, Asia, and Latin America. The Czech RMG was established by the Czech Myeloma Group in 2007 and comprises clinical data for 〉6000 MM pts enrolled at 19 Czech and 4 Slovak centers. Methods RRMM pts with 1-3 (INSIGHT MM) or ≥1 (RMG) prior therapies who had been treated with IRd were identified. INSIGHT MM pts required prospectively collected data on IRd therapy; pts who received another regimen or additional treatment within the same line of therapy as IRd were excluded. RMG pts from Czech centers who received IRd were included using the same eligibility criteria as the INSIGHT MM study. Individual pt-level data on demographics, disease characteristics, treatment history, effectiveness, and safety for IRd-treated RRMM pts from INSIGHT MM and the Czech RMG were integrated and analyzed. Best response and PFS were determined as per the assessment of the treating physician or local investigator, utilizing IMWG criteria. Descriptive analyses were performed on the integrated data as well as on data from INSIGHT MM and from the Czech RMG. PFS, TTNT, DOT, and OS were estimated using Kaplan Meier methodology. Results Overall, 163 IRd-treated RRMM pts from 9 countries were included in the analysis (50 INSIGHT MM, 113 Czech RMG); of these, 146 (90%) were from EUR, 16 (10%) from the US, and 1 (1%) from Taiwan. Median age was 67 (range 39-84) yrs, with 23 (14%) pts aged 〉75 yrs; 86 (53%) pts were male. At initial diagnosis, 38%/36%/26% of pts had ISS Stage I/II/III disease; median time from diagnosis to initiation of IRd treatment was 42.6 mos; 71% of pts had ECOG PS ≥1. Most pts (65%) had IgG MM, and 14% had extramedullary disease. Overall, 50%/30%/20% of pts received IRd as 2nd/3rd/≥4th-line therapy. The most common reasons for starting IRd therapy were relapse/progression (90%), including bone lesions (53%), and anemia (14%). Overall, 61% of pts had received prior stem cell transplant; prior therapies included bortezomib (bor) in 89% of pts, thalidomide (thal) in 42%, len in 21%, carfilzomib (car) in 11%, daratumumab (dara) in 3%, and pomalidomide (pom) in 2%. Median DOT was 14.0 mos; 101 (62%) pts were on treatment at data cut-off. Data on best response to therapy were available for 105 pts; among these, ORR (partial response or better) was 74%, with 31% ≥VGPR (Table); ORR with IRd as 2nd/3rd/≥4th-line therapy was 91%/57%/47%, including 41%/25%/11% ≥VGPR. Median time to first response was 1.1 mos for Czech RMG pts; median time to best response was 3.7 mos for INSIGHT MM pts. Overall, median PFS was 20.9 (95% CI: 13.0-28.7) mos, with a 12-mo rate of 65% (Table). Median PFS with 2nd/3rd/4th/〉4th-line therapy was NR/23.2/14.2/5.1 mos. Median TTNT was 26.2 (95% CI: 9.6-42.8) mos, with a 12-mo rate of 73% (Table). Overall, 37 (23%) pts received subsequent therapies including bor (24%), pom (24%), thal (16%), dara (16%), car (14%), or len (8%). Median OS was not reached, with 81% of pts alive at 12 mos (Table). Ixa and len dose reductions were required in 15% and 30% of pts, respectively, with 11% and 21% of pts, respectively, requiring dose reductions due to AEs (Table). Conclusions These findings show that the effectiveness of IRd in routine clinical practice, including an ORR of 74% and a median PFS of 20.9 mos, is comparable to the efficacy of IRd reported in the TOURMALINE-MM1 trial (ORR 78%, median PFS 20.6 mos). IRd is well tolerated in RRMM pts treated in routine clinical practice, with low rates of dose reductions due to AEs for ixa (11%) and len (21%). Table. Table. Disclosures Hajek: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Terpos:Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Chari:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Array Biopharma: Research Funding. Costello:Poseida Therapeutics, Inc.: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Puig:Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Leleu:Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Karyopharm: Honoraria. Berdeja:Celgene: Research Funding; Sanofi: Research Funding; Glenmark: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Genentech: Research Funding; Bluebird: Research Funding; Teva: Research Funding; Poseida Therapeutics, Inc.: Research Funding. Davies:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Abbvie: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; ASH: Honoraria; TRM Oncology: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Usmani:Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Hungria:Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria. Boccadoro:Amgen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Mundipharma: Research Funding; Celgene: Honoraria, Research Funding. Rifkin:McKesson: Equity Ownership; Boehringer Ingelheim: Consultancy; EMD Serono: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Sandoz: Consultancy; Amgen: Consultancy. Zonder:Takeda: Honoraria; Pharmacyclics: Other: DSMC; Alnylam: Honoraria; Coelum: Honoraria; BMS: Research Funding; Janssen: Honoraria; Celgene: Consultancy, Honoraria. Cook:Amgen, Bristol-Myers Squibb, GlycoMimetics, Celgene, Janssen and Takeda and Sanofi: Honoraria; Celgene, Janssen and Takeda: Research Funding. Ren:Takeda Pharmaceuticals International Co.: Employment. Cacioppo: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. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Maisnar:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, 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; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Monoclonal gammopathies are a disparate group of diseases from benign to malignant which are characterised by the proliferation of a single B cell clone that produces a homogeneous monoclonal immunoglobulin (M-Ig). The method of detection and quantification of the M-Ig will depend upon whether it is an intact immunoglobulin or present as serum free light chain only. Historically serum (SPEP) and urine (UPEP) electrophoresis were considered the gold standard for identifying intact M-Ig and FLC respectively. In 2001 the introduction of the Freelite test changed the diagnostic and monitoring paradigm. The assay is now recommended as a tool to diagnose and monitor patients with B cell disorders. However, the assay is sometimes confused with monospecific immunoassays for measuring total kappa and total lambda. Here we compare kappa & lambda Freelite with total kappa & lambda immunoassays alongside SPEP as tools to identify patients with monoclonal gammopathies. Materials and Methods Sera from 102 blood donors (55 males and 47 females, age range 18-67 years) and 103 patients with light chain associated gammopathies (44 males and 59 females, age range 38 to 88 years, 60 kappa / 43 lambda)taken during the course of their treatment were available. The sera was analysed retrospectively with FreeliteTM (The Binding Site Ltd, Birmingham, UK) on a SPAPLUSand Total Kappa &Lambda nephelometricassays (Beckman Coulter, USA) on an Immage.Monoclonality was identified by results falling outside of manufacturers normal ratio ranges (Freelite 0.256-1.65, Total light chain 1.53-3.29). Serum protein electrophoresis was performed and unexpectedly positive or negative results were assessed using immunofixation on the Hydrasys electrophoretic system (Sebia, France). Results Monoclonal production was identified in 80/103 light chain associated gammopathiesby Freelite, negative IFE confirmed the absence of monoclonal protein in 22/23 patients with normal FLC kappa/lambda ratios and 1/23 patients had an IgG lambda intact immunoglobulin. SPEP was positive in 30/103 patients, with total kappa/lambda immunoassays detecting monoclonal protein in just 26/103 samples. Freelite was positive in 6/102, SPEP in 2/102 and total kappa/lambda in 8/102 normal blood donor sera. Interestingly, in 1 patient with an abnormal FLC ratio and total kappa/lambda result had a lambda light chain identified using IFE.Comparisons between the performances of Freelite, Freelite + SPEP, Total kappa/lambda and total kappa/lambda + SPEP are shown in table 1). Conclusion In keeping with Kyle et al (1999) our study confirms the limitations of total kappa / lambda assays as tools to identify M-Igs. This is the first study looking to apply the recommended algorithm of Freelite + SPEP to the total kappa/lambda assays. The addition of SPEP to total kappa/lambda assays improved the performance to detect abnormalities, but even combined they were neither as sensitive, specific or accurate as the Freelite assay. Given the limitations of the total light chain assays identified in our study, it is important that physicians are aware of which assay is being utilised; one easy method to discriminate would be to look at the normal range of the assay being reported. Table 1: Comparison of Freelite, Freelite + SPEP, Total kappa/lambda, Total kappa/lambda + SPEP Freelite Freelite + SPEP Total Total + SPEP Sensitivity 77.67 81.55 25.24 43.69 Specificity 94.12 92.16 92.16 91.18 PPV 93.02 91.30 76.47 83.33 NPV 80.67 83.19 54.97 61.59 Accuracy 85.85 86.83 58.54 67.32 Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Despite the increase in overall survival in patients with multiple myeloma (MM) over the last decade as a result of the use of new chemotherapeutic agents, the immunomodulators (thalidomide and lenalidomide) are associated with a higher rate of venous thromboembolism (VTE), principally when associated with other chemotherapeutic drugs and erythropoietin (EPO). The incidence of VTE with isolated thalidomide is 3 to 4%, similar to the risk of the disease itself. The association of thalidomide with corticoids or anthracycline agents has led to an increase in the incidence of VTE to 12 and 34%, respectively. The introduction of low-dose aspirin, vitamin K inhibitors or low molecular weight heparin prophylaxis, according to the risk factors present upon diagnosis reduced the risk of thrombosis to 3 to 7%. Objectives: The objectives were to evaluate thrombotic events during the use of thalidomide as first-line treatment in symptomatic MM patients and the effectiveness of low-dose aspirin prophylaxis. Casuistic and Methods: This is a descriptive study of thrombotic events by means of a retrospective survey of patient files for MM patients who had been followed up on at the gammopathies outpatient unit at Santa Casa de Misericórdia de São Paulo from January 2009 to April 2014. The following induction therapy schedules with thalidomide for patients eligible or not for bone marrow transplantation were performed: thalidomide + dexamethasone (TD), cyclophosphamide + thalidomide + dexamethasone (CTD) and melphalan + prednisone + thalidomide (MPT). All of the patients received a dose of 100mg/day of the antiplatelet agent (aspirin) as prophylaxis. Results: In the aforementioned period, 219 patients had been diagnosed with symptomatic MM and of these, 149 patients had received thalidomide-based chemotherapy. The thalidomide group had a median age of 61 years (40 to 88). In the DS IIIA-IIIB stage, there were 131 (87.9%), 14 (9.4%) IIA-IIB, 1 (0.7%) IA and 3 (2%) had not been evaluated. According to the ISS Classification, 36 (24.2%) were ISS I, 41 (27.5%) II and 58 (38.9%) III, with 9.4% not evaluated. The most frequent isotope was IgG (56%). In relation to chemotherapy, 34 (22.8%) received TD, 98 (65.8%) CTD, 17 (11.4%) MPT. We identified 10 (6.7%) cases of thrombotic events in patients using thalidomide, thus distributed: 8 deep vein thrombosis (DVT), one case of DVT/ pulmonary embolism and one case of thrombophlebitis. Only one patient with thrombosis did not follow the prophylactic treatment at the service, which was 100mg/day of aspirin. The events occurred on average 72 days after initiating thalidomide use. Five cases were related to mobility reduction, 2 cases to obesity, 2 to smoking, 3 being ex-smokers, 3 to infection concomitant with the thrombotic event, 2 to diabetes and 1 case of previously treated breast cancer. All of the cases presented some associated risk factor. Conclusion and Discussion: The use of aspirin as prophylaxis in the group of MM patients being treated with thalidomide demonstrated efficacy in the control of risk for thrombosis. We observed 6.7% of VTE with the prophylactic use of low-dose aspirin in recently diagnosed MM patients without a history of thrombotic events, as described in the literature. Thalidomide is made available free of charge for MM treatment by the Brazilian public health system. Therefore, it is the main drug used in the MM treatment in Brazil. A better understanding of adequate thrombophylaxis according to the present risk factors is important for the optimization of the treatment of MM patients. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: In the randomized placebo controlled phase 3 trial PANORAMA 1 the pan-deacetylase inhibitor (pan-DACi) panobinostat combined with bortezomib and dexamethasone (PAN-BTZ-Dex) led to a statistically significant and clinically relevant increase in progression free survival in patients (pts) with relapsed or relapsed and refractory multiple myeloma (Pbo-BTZ-Dex; 12.0 vs 8.1 months; hazard ratio 0.63, P

Description: Introduction Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries. Objective To characterize the demographic and clinical features of patients with multiple myeloma from five LA countries (Brazil, Argentina, Chile, Mexico and Peru) and to create a LA database on MM; in addition to investigating the patterns of care for MM patients in Latin America. Patients and Methods This is an observational, non-intervention study, with a prospective evaluation of data. Eligible patients were diagnosed with multiple myeloma, between January 1, 2005, and December 31, 2007, at any one of the participating centers, regardless of disease stage or treatment modality. The follow-up period extended to at least 5 years for each patient (December 31, 2012). Results Eight hundred and seventy six patients were included. The median age was 60 years old (25-97), 53.4% male and 46.6% female. The median follow-up was 31.4 months, and the median overall survival was 57 months. The median overall survival to patients who received high-dose chemotherapy was 77 months and for patients who received conventional chemotherapy was 48 months (p

Description: Background The introduction of multiple novel agents and regimens for NDMM and relapsed/refractory MM (RRMM) has improved outcomes while increasing the complexity of treatment selection and disease management. The real-world effectiveness of many novel-agent-based regimens remains to be elucidated. INSIGHT MM (NCT02761187) is the largest global, prospective, observational MM study to date. It aims to understand global NDMM/RRMM disease and pt characteristics, treatment patterns, and clinical outcomes, as well as regional variations. Here we report data for 1056 NDMM pts enrolled from July 1, 2016 to April 27, 2018. Methods INSIGHT MM is enrolling ~4200 adult pts with NDMM/RRMM (1-3 prior therapies) from 15 countries; 9 in Europe (EU), 3 in Latin America (LA), the United States (US), and 2 in Asia. Pts will be followed prospectively for ≥5 yrs. Data are collected from hospital/clinic records at baseline (MM-specific disease characteristics, prior therapies) and every 3 mos (disease management, effectiveness, safety). Results At data cut-off, 1056 NDMM pts had been enrolled from 14 countries, including 495 (47%) from EU, 361 (34%) from the US, 112 (11%) from LA, and 88 (8%) from Taiwan. Median age at enrollment was 64 (range 32-89) yrs and 139 (13%) pts were aged 〉75 yrs (14%/12%/11%/13% in EU/US/Taiwan/LA); 57% of pts were male (60%/58%/61%/39% in EU/US/Taiwan/LA); 72%, 13%, and 8% were White/Caucasian, Asian, and Black/African American, respectively. Overall, 62% of pts were treated at academic centers and 38% in community settings. Based on accrual at data cut-off, regional differences were observed, with more pts treated at academic centers in EU/Taiwan (88%/91%) vs the US/LA (30%/25%). 87% of pts were treated outside of clinical trials (88%/82%/95%/98% in EU/US/Taiwan/LA). Bone pain (32%, including 33%/28%/40%/37% in EU/US/Taiwan/LA), weakness/fatigue (anemia; 11%, including 12%/10%/6%/18% in EU/US/Taiwan/LA), and kidney problems (5%, including 3%/3%/17%/2% in EU/US/Taiwan/LA) were the most common reasons for pts seeking care; 32% (36%/32%/22%/24% in EU/US/Taiwan/LA) were asymptomatic at diagnosis. At diagnosis, 27%/26%/31% of pts had physician-reported ISS Stage I/II/III MM, and 88% had ECOG PS 0-1; 8% of pts had hypercalcemia, 34% creatinine clearance 3 bone lesions. The most common reasons for initiating therapy were the presence of CRAB criteria, e.g. bone involvement (54%) and anemia (37%). At start of treatment, fixed-duration therapy, treat-to-best-response, and treat-to-progression approaches were planned for 38%, 29%, and 31% of pts, respectively. The most frequently administered regimens are shown in the Table; 20%/66% of pts received a doublet/triplet. V-based regimens were the most frequently used. Regional differences in regimen selection are emerging: among IMiDs, T is most commonly prescribed in EU, Taiwan, and LA; R is more common in the US. After a median follow-up of 9.3 mos, 72 (7%) pts had discontinued the study, most often due to death (57%), consent withdrawal (14%), or change of treatment provider (11%). At data cut-off, data for 236 (22%) pts who received 1st-line ASCT were available (median age 60 yrs; 12%/63%/25% of pts aged 65 yrs). Of these, 64% received ASCT at academic centers; 42% of pts each in EU and the US received ASCT vs 11% in Taiwan and 4% in LA. The most frequently administered regimens in ASCT-eligible (n=429) vs ASCT-ineligible (n=571) pts were VC±d (21% vs 21%), VR±d (19% vs 17%) and VT±d (17% vs 10%). At data cut-off, 115 NDMM pts had progressed to 2nd-line therapy; 99 pts received a PI with 1st-line therapy, of whom 33 (33%) then received a PI-based regimen in 2nd line; 61 pts received an IMiD with 1st-line therapy, of whom 35 (57%) then received an IMiD-based regimen in 2nd line. Among 1st/2nd-line pts, 2%/12% received monoclonal antibody therapy. Conclusions PIs and IMiDs remain the global backbones of MM therapy, with V-based regimens most commonly used in NDMM pts, regardless of intended transplant status. These data from INSIGHT MM are beginning to elucidate regional differences in disease presentation and treatment selection, including higher numbers of pts receiving ASCT in the US/EU vs Taiwan/LA, which are likely reflective of differences in healthcare systems and access to MM treatments in the participating countries. Future studies will evaluate the impact of these regional variations on outcomes. Table. Table. Disclosures Usmani: Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Hungria:Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Leleu:Karyopharm: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Davies:Abbvie: Consultancy; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; TRM Oncology: Honoraria; ASH: Honoraria; MMRF: Honoraria. Costello:Poseida Therapeutics, Inc.: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Rifkin:Takeda: Consultancy; EMD Serono: Consultancy; McKesson: Equity Ownership; Celgene: Consultancy; Amgen: Consultancy; Sandoz: Consultancy; Boehringer Ingelheim: Consultancy. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding. Chari:Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, 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; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; The Binding Site: Consultancy; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Puig:Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding. Boccadoro:Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding. Cook:Bristol-Myers Squibb: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Berdeja:Teva: Research Funding; Janssen: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Bluebird: Research Funding; Genentech: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Sanofi: Research Funding. Zonder:Takeda: Honoraria; Coelum: Honoraria; BMS: Research Funding; Celgene: Consultancy, Honoraria; Alnylam: Honoraria; Janssen: Honoraria; Pharmacyclics: Other: DSMC. Abonour:Prothena: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Hajek:Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Spencer:Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. Omel:Takeda Oncology: 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. Demers:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Ren:Takeda Pharmaceuticals International Co.: Employment. Skacel:Department of Hematology, Charles University General Hospital, Prague, Czech Republic: Other: Affiliation; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Terpos:Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding.

Description: Background: Isatuximab (ISA) targets CD38-expressing tumor cells through a combination of activities, including antibody-dependent cellular cytotoxicity, direct pro-apoptotic activity, and complement-dependent cytotoxicity. A phase I study evaluating ISA monotherapy demonstrated promising clinical activity in 35 patients with relapsed/refractory multiple myeloma (RRMM) (Martin T et al, J Clin Oncol 2014; 32:8532). This is an ongoing phase II study (NCT01084252) with 2 stages: stage 1 to select the dose for stage 2 of the study, and stage 2 to assess efficacy and safety of ISA monotherapy or in combination with dexamethasone in RRMM. In stage 1, patients were randomized to 1 of 3 dose groups: ISA 3 mg/kg Q2W, 10 mg/kg Q2W × 2 cycles then Q4W, or 10 mg/kg Q2W. Based on pharmacokinetic data, a fourth dose of 20 mg/kg QW × 4 doses then Q2W was added. The overall response rates (ORRs) for the 4 dosing schemes were 4% (1/23), 20% (5/25), 29% (7/24), and 24% (6/25), respectively. Based on these results, a dose of 20 mg/kg QW for cycle 1 followed by 20 mg/kg Q2W in subsequent cycles was chosen for stage 2 of the study (Richter J et al, J Clin Oncol 2016;34:8005). Here, we report the baseline characteristics and demographic data from stage 2 at the selected dosing scheme from stage 1. Full safety and efficacy data will be presented at the meeting. Methods: This study enrolled patients with MM who had previously received an immunomodulatory drug and a proteasome inhibitor. Patients received ISA monotherapy (20 mg/kg on Day 1, 8, 15, and 22 [QW] of cycle 1 followed by 20 mg/kg on Day 1 and 15 [Q2W] of subsequent cycles) or ISA in combination with dexamethasone (40 mg/day [20 mg/day in patients ≥75 years old]). The primary objective was to evaluate the activity of ISA as monotherapy and in combination with dexamethasone in patients with RRMM in terms of ORR. Results: A total of 165 patients received at least 1 cycle of treatment. Median age was 67 (37-85) years. Median time from diagnosis to first dose was 5.35 (0.7-23.0) years. Median number of prior lines was 4 (2-11) and median number of prior regimens was 6 (2-17). Patients received a median of 5 (1-17) cycles of treatment, with a median duration of exposure of 22 (1-69) weeks. Discontinuation occurred in 106 (64.2%) patients due to adverse events (15 patients, 9.1%), disease progression (85 patients, 51.5%), or patient decision (6 patients, 3.6%). Conclusion: The full efficacy and safety data for this heavily pre-treated RRMM population will be available for presentation at the meeting. Funding: Sanofi Disclosures Dimopoulos: Janssen: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Bringhen:Celgene: Honoraria; Amgen: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Takeda: Consultancy; Bristol-Myers Squibb: Honoraria. Anttila:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Capra:Janssen: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Research Funding; Sanofi: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding. Cavo:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cole:University of Michigan: Employment; Cancer Support Community myeloma advisory board: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel; Takeda: Honoraria. Hungria:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Jenner:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vorobyev:Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Biocad: Consultancy; Takeda: Speakers Bureau; BMS: Speakers Bureau; Astellas: Speakers Bureau. Yanez Ruiz:Universidad de la Frontera: Employment. Yin:Sanofi: Employment. Hamlett:BDM Consulting Inc.: Employment; Sanofi: Consultancy. Vij:Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.