Abstract: *Equally Contributed Introduction: Recent studies show better progression-free (PFS) and overall survival (OS) for newly diagnosed multiple myeloma (NDMM) pts achieving MRD negativity by multicolor flow cytometry (MFC) or next-generation sequencing (NGS). Here, we report on the comprehensive assessment of MRD in a uniformly treated cohort of 45 MM patients (Korde et al. ASH 2013). Methods: 45 NDMM pts were treated with 8 cycles of combination therapy (carfilzomib, lenalidomide and dexamethasone) followed by 2 years of maintenance lenalidomide. Median potential follow-up was 17.3 mos. All patients were evaluated by NGS by LymphoSIGHT™ method. Briefly, using universal primer sets, we amplified immunoglobulin heavy and kappa chain (IGH and IGK) variable, diversity, and joining (VDJ) gene segments from genomic DNA obtained from CD138+ BM cell lysate or cell free bone marrow (BM) aspirate at baseline. A MM clonotype was defined as an immunoglobulin rearrangement identified by NGS at a frequency 〉 =5%. MRD assessment by NGS, MFC and PET was repeated when patients achieved a complete response (CR) or completed 8 cycles of therapy. In a subset of patients, we performed NGS in peripheral blood (plasma) at baseline and after 2 cycles of treatment. Results: 40/45 (89%) of pts achieved VGPR or better after combination therapy. At least one clonal rearrangement was identified in 31/34 (91%) of BM CD138+ cell samples and in 34/45 (76%) of cell free BM aspirates; overall clonal rearrangement was detected in 37/45 (82%) bone marrow aspirates at baseline. Repeat MRD assessment at CR or the completion of 8 cycles in 32 pts show residual disease in cell free BM aspirates by NGS in 18 (56% of pts tested and 40% of the total study population). Estimated 12-mo and 18-mo PFS for MRD neg vs. pos by NGS was 100% vs 94% and 100% vs 84%, respectively (p=0.025). MFC testing for MRD was feasible in 43/44 pts (98%). PFS probabilities at 12-mo and 18-mo for flow neg vs pos was 100% vs 79% and 100% vs 63%, respectively (p=0.0022). Among pts assessed by both MRD methods (n=31), 23 samples were concordant (9 pos and 14 neg); among 8 discordant cases, all were positive by sequencing and negative by flow (p=0.0078). Abnormal PET scans were noted in 38/45 (84%) of pts at baseline. 24/43 (56%) pts at CR or after 8 cycles of CRd had a neg/dec PET response and 19/43 (44%) pts had a pos/partial PET response. At 12-mo and 18-mo, PFS by a neg/dec PET response vs pos/partial PET response was 100% vs 89% and 92% vs 89%, respectively (p=0.54). Furthermore, in 14 pts, we performed NGS in peripheral blood samples collected at baseline. At least one MM clonotype identified in baseline BM was detectable in corresponding plasma sample in 13/14 pts. Number of myeloma-specific molecules per million diploid genomes in the plasma was 3-log fold lower than in the BM (median 252 vs 730,950 MM specific clonal molecules per million diploid genomes). After 2 cycles of CRd treatment, 12/13 pts were still pos by serum electrophoresis and/or immunofixation while only 1 had detectable myeloma clonotypes in the plasma. Conclusions: This prospective evaluation of MRD testing in MM has several key findings: 1. Detection of myeloma-specific clonotypes by NGS of the Immunoglobulin VDJ segments in the BM is feasible in majority of pts with NDMM. 2. MRD detection by NGS compares favorably to MFC since all pts with residual disease by MFC are also MRD positive by sequencing; an additional 8 pts who were MRD negative by flow MFC were MRD positive by sequencing. 3. MRD negativity by MFC and NGS are both associated with significantly better PFS. 4. Detection of myeloma-specific clonotypes by NGS of the immunoglobulin VDJ segments (i.e. cell free DNA) in the peripheral blood plasma is feasible in NDMM pts at diagnosis; however, since tumor load in the plasma is 〉 2000-fold lower than in the BM; using standard volumes of peripheral blood (plasma), the levels of myeloma-specific clonotypes were too low to be quantified already after 2 cycles of combination therapy. This was true despite presence of positive serum electrophoresis and/or immunofixation. Additional studies to understand the dynamics of the myeloma clonotype level in peripheral blood plasma are necessary to determine optimal MRD testing regimen. Disclosures Faham: Sequenta, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Moorhead:Sequenta, Inc.: Employment.

Abstract: Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

Abstract: Background Monoclonal gammopathy of undetermined significance (MGUS) is a precursor condition to multiple myeloma and other lymphoproliferative disorders. In individuals with MGUS, the average risk of progression to a lymphoproliferative disorder has been estimated to be 1% per year, however, most previous studies have been performed on clinically established cohorts and very few have been population-based. A high monoclonal (M)-protein concentration, non-isotype IgG, and skewed free light chain (FLC) ratio are routinely taken into account when assessing risk for progression. Other risk factors have also been identified, such as low serum albumin. Methods The cohort under study consisted of 299 individuals, 158 men and 141 women, with MGUS, identified through screening the participants of the population-based, longitudinal AGES-Reykjavik Study using serum protein electrophoresis and FLC assessment. The median age was 78 years (range 67-93 years). The outcome was first incidence of lymphoproliferative disorder, denoting multiple myeloma, lymphoma, amyloidosis, lymphocytic leukemia, plasmacytoma, and Waldenström's macroglubulinemia. Information on outcomes was supplemented by cross-linkage to national registries, and median follow-up time was 8.8 years. A Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of lymphoproliferative disorders. Results were adjusted for serum albumin in categories (below 35 g/L, 35-40 g/L, or above 40 g/L), M-protein concentration (above or below 15 g/L), FLC ratio, levels of free light chains, use of statins, smoking status, renal function in categories, and M-protein isotype. The multivariate model was reduced in a step-wise manner to a final model with only significant covariates. Results During follow-up, 26 of 299 individuals with MGUS proceeded to develop a lymphoproliferative disorder, representing a cumulative risk of 8.7% and an annual risk of 1.0%. MM occurred in 17 of 218 individuals with non-IgM MGUS, representing a cumulative risk of 7.8% and an annual risk of 0.9%. In multivariate analysis, the final model contained serum albumin, M-protein concentration, and isotype A versus all other isotypes. Low serum albumin (HR = 6.3, 95% CI 1.0-40.6 for 〈 35 g/L, and HR = 3.9, 95% CI 1.1-14.2 for 35-40 g/L), high M-protein concentration (HR = 4.1, 95% CI 1.2-14.0), and isotype A (HR = 5.8, 95% CI 1.6-21.0) were significantly associated with risk of progression. In a similar model for progression to multiple myeloma only, low serum albumin, high M-protein concentration, and isotype A were also significantly associated with risk of progression, although the impact of low serum albumin was greater (HR = 33.1, 95% CI 2.4-462.2 for 〈 35 g/L, HR = 10.97, 95% CI 1.4-88.3 for 35-40). When assigning a risk score for progression where 1 point each was assigned for isotype IgA, serum albumin 〈 35 g/L, and M-protein concentration 〉 15 g/L, the HRs for individuals with 1 point was 3.9 (95% CI 1.6-9.9), and for 2 points 10.02 (95% CI 2.3-43.3). No individual had 3 points. For Kaplan-Meier estimates from risk scores, see Figure. Summary and conclusions In this large, population-based screening study, we found an annual risk of progression from MGUS to lymphoproliferative disease of 1%. Low serum albumin, high M-protein concentration, and M-protein isotype A were all independent risk factors for progression. Our results are in line with results from previous studies where a low serum albumin at MGUS diagnosis also has been associated with shorter survival and/or malignant transformation. Results from our study contradict previous studies that have pointed to skewed FLC ratio as an important risk factor for progression; in our study, a skewed FLC ratio was not significantly associated with risk of progression when adjusted for other covariates. The findings in our study suggest that serum albumin is important to take into account when assessing the risk of progression for individuals with MGUS. Figure 1 Kaplan-Meier estimates for risk of progression, by risk score. Figure 1. Kaplan-Meier estimates for risk of progression, by risk score. Disclosures Korde: Medscape: Honoraria. Landgren:Merck: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Research Funding; Medscape Myeloma Program: Honoraria; BMS: Honoraria; Celgene: Honoraria, Research Funding.

Abstract: INTRODUCTION Using Carfilzomib, Lenalidomide and Dexamethasone (KRd) combination therapy in newly diagnosed multiple myeloma patients lead to ~40% minimal residual disease (MRD) negativity rate. Here, we use KRd in combination with daratumumab (DKRd); and treatment response is assessed with extensive correlative science including parallel bone-marrow-based and blood-based MRD tracking, together with targeted DNA sequencing of baseline bone marrow samples. Primary end-point is to rule out 60% and to target up to 80% MRD negativity rate. METHODS This is a single-arm, Phase II clinical trial based on Simon's optimal two-stage design. The first cohort (twice-a-week carfilzomib) (N=41) has the following treatment schedule: 8 cycles of treatment; 28-day cycles with carfilzomib 20/36 mg/m2 days 1, 2, 8, 9, 15 and 16; lenalidomide 25 mg days 1-21; dexamethasone 40 mg weekly cycles 1-4, 20 mg after cycle 4; and daratumumab 16 mg/kg days 1, 8, 15, and 22 cycles 1-2, days 1 and 15 cycles 3-6, and day 1 cycles 7-8. The second cohort (once-a-week carfilzomib) (N=41): 8 cycles of treatment; 28-day cycles with carfilzomib 20/56 mg/m2 days 1, 8, and 15; lenalidomide, dexamethasone, and daratumumab are given at the same doses/schedules as the first cohort. For fit patients, stemcell collection is recommended after 4 to 6 cycles of therapy; DKRd therapy is resumed after collection to a total of 8 cycles DKRd. Treatment response is being assessed with parallel bone-marrow-based (10-color single tube flowcytometry, invivoscribe V(D)J sequencing) as well as blood-based (MALDI-TOF and QTOF-mass spectrometry [MS]) for MRD tracking. Baseline bone marrow samples are evaluated with targeted DNA sequencing for FISH-Seq and somatic mutational characteristics (myTYPE). Here, we present the first stage (N=28) of the first cohort (twice-a-week carfilzomib). We are waiting for the results to mature before the second stage (N=13) of the first cohort can open. The second cohort (once-a-week carfilzomib) is opening for enrollment in August 2018 (N=41). RESULTS The first stage of the first cohort is fully enrolled; 28 patients meeting eligibility criteria were enrolled onto study (14 males, 14 females) between October 2017 and July 2018. Baseline characteristics include; median age 60 years (range 32-80 years); 12(43%) patients had high-risk FISH/SNP signature defined as one or more of the following: 1q+, t(4,14), t(14,16), t(14,20), and 17p-. At the submission of this abstract, 20 patients have completed one or more cycles DKRd; among these, 3 patients have completed all 8 cycles. The median number of cycles delivered is currently 4 (range 1-8). Full assessments with MRD assays have been completed in 3 patients: -Pt #1 obtained complete response (CR) after 3 cycles, and workup after the last cycle of therapy showed MRD-negativity (by 10-color single tube flowcytometry and V(D)J sequencing) in the bone marrow; and peripheral blood (serum) was negative by MALDI-TOF MS after completion of cycle 2. -Pt#2 obtained CR after 4 cycles, however, workup after cycle 5 showed MRD-positivity (by 10-color single tube flowcytometry and V(D)J sequencing) in the bone marrow; and peripheral blood (serum) was positive by MALDI-TOF MS throughout the end of the last cycle. -Pt#3 obtained CR after 4 cycles and after 6 cycles both 10-color single tube flowcytometry and V(D)J sequencing showed MRD-negativity in the bone marrow. However, MALDI-TOF MS detected small abnormal serum proteins in peripheral blood and remained positive throughout the end of cycle 8. Overall, the DKRd therapy is well tolerated and it has similar toxicity profile as KRd. Grade 〉 3 adverse events were hypotension, musculoskeletal deformity, back pain, dyspnea, lung-infection, and febrile neutropenia. So far, 5 patients underwent dose reductions of lenalidomide. CONCLUSIONS In this pre-planned interim analysis of our phase II study, we show that DKRd is a highly effective and well tolerated combination therapy for newly diagnosed multiple myeloma patients. Based on small numbers of patients who have completed the planned DKRd cycles and been evaluated by bone marrow-based MRD and peripheral-blood based assays, we show that highly sensitive protein assays may allow longitudinal MRD tracking in peripheral-blood. At the meeting, we will present updated results using longitudinal testing with MALDI TOF-MS and QTOF-MS on the entire cohort. Disclosures Landgren: 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; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Pfizer: Consultancy; Karyopharm: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees. Lesokhin:Takeda: Consultancy, Honoraria; Janssen: Research Funding; Squibb: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Serametrix, inc.: Patents & Royalties: Royalties. Mailankody:Juno: Research Funding; Physician Education Resource: Honoraria; Takeda: Research Funding; Janssen: Research Funding. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Hassoun:Oncopeptides AB: Research Funding. Shah:Amgen: Research Funding; Janssen: Research Funding. Arcila:Invivoscribe, Inc.: Consultancy, Honoraria. Ho:Invivoscribe, Inc.: Honoraria. Korde:Amgen: Research Funding.

Abstract: Background The use of immunomodulatory agents and proteasome inhibitors in newly diagnosed multiple myeloma (NDMM) patients has improved outcomes and led to their widespread use as induction regimens independent of transplant eligibility. Although the overall toxicity profiles of these regimens are considered favorable, their prolonged use warrants a heightened vigilance for toxicities during therapy, and treating physicians need to carefully balance efficacy and toxicity profiles for each patient. Given that patients enrolled on clinical trials, per eligibility criteria, are less frail and/or have fewer comorbidities than patients in the general population, we were motivated to conduct a large study designed to define the safety profiles of the most commonly used induction regimens in the US, based on real-world evidence data. Methods We identified 185 consecutive NDMM patients treated with bortezomib, lenalidomide, and dexamethasone (VRd) vs. carfilzomib, lenalidomide, and dexamethasone (KRd) at MSKCC between 2015 and 2019. By reviewing all available data for these patients, we defined the incidence of cardiopulmonary toxicities, hypertension, renal complications, and peripheral motor or sensory neuropathy. Results A total of 81 and 104 patients were treated with VRd and KRd induction, respectively (Table 1). The VRd (compared to KRd) group had a smaller proportion of patients with high-risk cytogenetics (36% vs. 55%, P=0.01); yet, the & gt;CR rate was lower in the VRd (compared to KRd) group (28% vs. 45%, P=0.02) (Table 2). Table 3 summarizes select toxicities. The incidence of cardiopulmonary AEs was similar in both groups: 12% (N=9) and 10% (N=11) in the VRd and KRd groups, respectively, with the majority limited to grade 1 and 2 (P=1.00); observed cardiac toxicity was reversible in 8 of 9 (89%) vs. 9 of 11 (82%) patients. Renal toxicity was rare in both groups (2% vs. 4% for VRd vs. KRd, P=0.70). New onset or worsening of pre-existing (at baseline) neuropathy was significantly (P & lt;0.00001) more common in the VRd group with 45 (56%) patients developing all grades of peripheral neuropathy. In the KRd group, 13 (12%) patients reported new onset or worsening of pre-existing (at baseline) grade 1 peripheral neuropathy during therapy, and it resolved in 9/13 patients after completing therapy. Of the 45 patients with neuropathy in the VRd group, 16/45 (35%) developed sensory alteration or paresthesia (including tingling) interfering with function and/or symptomatic weakness interfering with function, or more severe forms of neuropathy (grade & gt;2), and 26/45 (58%) patients developed chronic neuropathy after completion of induction therapy. These patients required various interventions, including opiates (N=7), pregabalin/gabapentin/duloxetine (N=17), rehabilitation/physical therapy (N=2), assistive devices such as canes, walkers, and wheelchairs (N=3). None of the patients treated with KRd had new onset neuropathy requiring pain medication. In the VRd group, neuropathy resulted in treatment discontinuation for 6 (7%) patients. Overall, 9% and 4% of patients treated with VRd and KRd, respectively, had treatment discontinuation due to AEs (P=0.22). There were no deaths in the two groups. Conclusion Using real-world evidence data, we defined the safety profiles of VRd and KRd. In sharp contrast to clinical trials mandating recurrent IV fluids before/after administration of carfilzomib, we use optimized IV fluid management (250 ml saline before dose 1 of cycle 1, thereafter no IV fluids) coupled with baseline work-up, including EKG and echocardiogram, for all patients treated with KRd. Therefore, we did not observe excess rates of cardiopulmonary or renal AEs with KRd, and the majority were reversible. In the VRd group, 45 (56%) patients developed new onset or worsening neuropathy, and a third of these developed sensory alteration or paresthesia interfering with function and/or symptomatic weakness interfering with function, or more severe forms of neuropathy. Overall, about 30% of all VRd treated patients developed chronic neuropathy after induction therapy, including disabling neuropathy in some patients and often with need for continued pain treatment. Neuropathy resulted in treatment discontinuation for 7% of patients treated with VRd. These real-world evidence data demonstrate the general tolerability and efficacy of KRd induction, with less severe neuropathy compared to VRd. Disclosures Hultcrantz: Daiichi Sankyo: Research Funding; Amgen: Research Funding; Intellisphere LLC: Consultancy; GSK: Research Funding. Korde:Amgen: Research Funding; Astra Zeneca: Other: Advisory Board. Lesokhin:GenMab: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Juno: Consultancy, Honoraria; Janssen: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding. Mailankody:Allogene Therapeutics: Research Funding; Physician Education Resource: Honoraria; PleXus Communications: Honoraria; Takeda Oncology: Research Funding; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding; Janssen Oncology: Research Funding. Hassoun:Takeda: Research Funding; Novartis: Consultancy; Celgene: Research Funding. Shah:Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Scordo:Kite - A Gilead Company: Other: Ad-hoc advisory board; Omeros Corporation: Consultancy; Angiocrine Bioscience, Inc.: Consultancy, Research Funding; McKinsey & Company: Consultancy. Chung:Genentech: Research Funding. Shah:Amgen Inc.: Research Funding; Janssen: Research Funding. Lahoud:MorphoSys: Other: Advisory Board. Giralt:Actinuum: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Quintiles: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Jazz: Research Funding; Kite: Research Funding; Sanofi: Research Funding; Adienne: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Seattle Genetics: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Seattle Genetics: Research Funding; Juno: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Abstract: Background : TheHevylite assay (HLC Assay) is a novel assay using antibodies that recognize unique conformational epitopes presented by the association of the heavy and light chain constant regions of intact immunoglobulins (Ig) allowing quantitative measurement of each Ig class concentration and generating ratios for each pair (e.g. IgGK/IgGL). Recent studies indicate that HLC Assay can enhance the ability to detect and quantify monoclonal Ig, potentially providing greater sensitivity for detection of minimal residual disease or early relapse after treatment and providing a prognostic indicator of progression free survival (Ludwig, H. et al. Leukemia (2013) 27, 213-219; Kraj, M. et al. Adv Clin Exp Med 2014, 23, 1, 127-133). While HLC Assay could simplify and enhance the assessment of monoclonal protein response in multiple myeloma (MM), its utility as compared to standard assays (SA) (Serum Protein Electrophoresis (SPEP) and Immunofixation (IF)) is not well established. The goal of this retrospective study was to compare the performance of these tests in patients with MM seen at Memorial Sloan Kettering Cancer Center. Methods : We have previously reported on the patterns of relapse and/or progression (R/POD) in 179 patients with MM transplanted between 2001 and 2009 at MSKCC and determined the precise date of R/POD based on IMWG standard clinical criteria using serum and urine PEP and IF, as well as Free Light Chain Assay (FLCA) (Zamarin, Bone Marrow Transplant, 2013). Serum samples from 63 of these patients, collected at the time of R/POD and/or at time points preceding R/POD were analyzed by HLC Assay and compared to results obtained by SA. Results : Among the 63 patients, 22 had IgA and 41 had IgG isotype. Overall, 207 samples were available for all 63 patients, including 72 IgA and 135 IgG samples. Figure 1 shows the concordance of Hevylite ratio (on the Y-axis) with the results obtained by SA (on the X-axis), for IgA and IgG samples, respectively. These graphs reveal an excellent association between HLC Assay and SA results in the IgA samples: all IgA samples revealing an M spike by SPEP had an abnormal HLC ratio even for low M spike levels (between 0 and 0.5 g/dL). Among IgA samples with a monoclonal band detectable by IF, 43 out of 48 samples also had an abnormal ratio by HLC Assay; and among samples with no detectable band by IF, 18 out of 24 had a normal ratio by HLC Assay (sensitivity 90%, specificity 75%, p 〈 0.001) (Table 1, Panel 1). Interestingly, when looking at samples taken prior to relapse in IgA patients having achieved CR, HLC Assay was abnormal in 4 out of 7 patients while SA was still reported as normal. In contrast, the lack of association between the SA and HLC Assay is striking for the IgG samples, with poor sensitivity for the HLC Assay to detect monoclonal gammopathies with M spikes below 1 g/dL on SPEP. Among IgG samples with a monoclonal band detectable by IF, only 48 out of 89 samples also had an abnormal ratio by HLC Assay; while among samples with no detectable band by IF, 40 out of 46 had a normal ratio by HLC Assay (sensitivity 53% and specificity of 86% , p 〈 0.001) (Table 1, Panel 2). Conclusions: Although retrospective, this analysis suggests the following: 1) HLC Assay may be more sensitive than IF or SPEP in patients with IgA disease, as it can detect an abnormal HLC ratio at a time prior to relapse by SA, when IF and SPEP are still normal; 2) HLC Assay appears to be less useful in IgG patients, as its sensitivity in these patients appears much lower than IF; 3) There is a need for further detailed analysis on larger prospective cohorts to test the utility of HLC Assay compared to SA in the management of multiple myeloma patients, especially those with IgA disease. Figure 1 Association between HLC Assay and SA (SPEP/IF) results in patients with IgA disease. Figure 1. Association between HLC Assay and SA (SPEP/IF) results in patients with IgA disease. Figure 2 Association between HLC Assay and SA (SPEP/IF) results in patients with IgG disease. Figure 2. Association between HLC Assay and SA (SPEP/IF) results in patients with IgG disease. Disclosures Hassoun: Celgene: Research Funding; Binding Site: Research Funding; Novartis: Consultancy; Takeda: Consultancy, Research Funding. Kazunori:Binding Site: Research Funding. Landau:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx/Amgen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy; Spectrum Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Korde:Medscape: Honoraria. Landgren:Takeda: Honoraria; Amgen: Honoraria, Research Funding; BMS: Honoraria; Medscape Myeloma Program: Honoraria; Merck: Honoraria; Celgene: Honoraria, Research Funding.