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Background: The treatment of Multiple Myeloma (MM) has evolved significantly in the past decade with the introduction of novel agents and drug combinations, thus enhancing treatment efficacy and allowing more patients to achieve complete response (CR). This has created a need to identify surrogates for depth of treatment response. Serum free light chain (sFLC) ratio normalization has been shown to be prognostic for progression free survival as well as overall survival in patients achieving a complete response to therapy. Consequently, it has been incorporated as a defining feature for stringent CR, along with lack of clonal plasma cells by immunohistochemistry (IHC) or low sensitivity flow cytometry. The routine use of multiparametric flow cytometry with higher sensitivity to detect residual disease than IHC or the older 4-color flow cytometry, has raised the question as to whether sFLC ratio is still a valid indicator of response depth. Moreover, in nearly half of the patients with an abnormal sFLC ratio after treatment, the abnormality is secondary to suppression of one or both serum light chains. Therefore, we designed a retrospective study to address these issues. Patients and Methods: This is a retrospective study using the Multiple Myeloma Database at Mayo Clinic, Rochester. We included patients who, after any line of therapy, had negative serum and urine immunofixation and absence of clonal bone marrow plasma cells by flow cytometry (PC-PRO), which has a sensitivity of >10-4. Simultaneous sFLC data was also extracted. Patients were grouped into three categories based on their sFLC ratios: 1) normal ratio (normal), 2) abnormal ratio due to suppression of the uninvolved light chain (LC), involved LC, or both (Abn-suppressed) and 3) abnormal ratio due to elevation of the involved LC (Abn-inv elevated). The primary endpoint was the median time to next treatment (TTNT), defined as the time from sample collection to the time of initiation of the subsequent therapy or time of last follow up if a subsequent line of treatment was not initiated. Results: The cohort consisted of 510 patients. 285 (56%) were males and 225 (44%) females. Median age was 61 years (IQR: 55-67). Median Follow-up was 41 months. The last treatments administered prior to data collection included stem cell transplant (SCT) (with or without maintenance) in 290 (57%) patients, and non-SCT regimens in the others. The sFLC ratio was normal in 337 (66%) and abnormal in 173 (34%) patients. Among the patients with abnormal sFLC ratios, 81 had elevated involved LC, 25 had suppression of the involved LC, 45 had suppression of the uninvolved LC and 22 had suppression of both LCs. We first examined the TTNT for the three groups and found that the TTNT was identical for those with a normal ratio and those with an abnormal ratio due to suppression of one or both light chains (Figure 1). So, we combined these two groups (Normal-Abn suppressed) and compared their outcomes to the patients with abnormal sFLC ratio due to elevated involved LC. The Abn-inv elevated group had a shorter TTNT as shown in Figure 2 (log-rank 0.06, Wilcoxon <0.01). The Abn-inv elevated group also had decreased overall survival compared to the other group (log-rank: 0.05, Wilcoxon: 0.01) (Figure 3). Conclusion: This study provides 2 important observations. First, patients with an abnormal ratio due to suppression of one or both LCs have outcomes similar to those with a normal ratio, suggesting a need to clarify the current definition of stringent CR. Second, the study suggests an important prognostic value for an abnormal sFLC ratio due to elevated involved LC, suggesting this as an important surrogate for depth of response. Disclosures Kapoor: Janssen: Research Funding; Takeda: Honoraria, Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Glaxo Smith Kline: Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Gertz:Ionis: Honoraria; Alnylam: Honoraria; Prothena: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Spectrum: Honoraria, Research Funding. Lacy:Celgene: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Leung:Takeda: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Introduction: High-risk multiple myeloma can be defined by the presence of specific cytogenetic abnormalities (structural) or by characteristic changes in bone marrow and peripheral blood biomarkers (functional). While both entities are characterized by therapeutic resistance, frequent disease relapses, and adverse survival outcomes, the underlying molecular mechanisms remain incompletely understood. Methods: We performed gene expression profiling (GEP) using an Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray on CD138+ bone marrow cells from 137 patients diagnosed with multiple myeloma between 2004 and 2012. All patients underwent Fluorescence In-situ Hybridization (FISH) evaluation, plasma cell labeling, International Staging System (ISS) risk stratification, and GEP prior to initiating treatment with novel agents. The presence of del(17p), t(4;14), t(14;16), and t(14;20) on FISH, a plasma cell labeling index (PCLI) > 2%, and ISS stage III were considered high-risk abnormalities: FISH-HR (n = 15, structural high-risk, at least one high-risk FISH lesion), PCLI-HR (n = 20; functional high-risk, PCLI > 2%), and ISS-HR (n = 12; functional high-risk, ISS stage III). For each HR group we sampled standard risk (SR) controls in a 4:1 ratio. After data quality control and normalization, differential gene expression was estimated using limma. Statistical significance was adjusted for multiple comparisons using a false discovery rate-based approach for genome-wide experiments (q-value). We employed PANTHER pathway analysis for the differentially expressed genes in each HR group. We implemented a simple gene expression score (GES) by calculating the sum of quartiles of the normalized gene expression values for genes differentially expressed in more than one HR group (GES = ΣUP(quartile - 1) + ΣDN(4 - quartile)) and externally validated its prognostic significance (UAMS TT2 / TT3, GSE24080). Survival outcomes were analyzed using the methods described by Kaplan, Meier, and Cox. Computation and visualization were performed in R. Results: Median age at diagnosis was 63 years (32 - 87), 53% of the patients were male. High-risk disease was associated with inferior overall survival, regardless of the used definition (left Kaplan-Meier plots): FISH-HR (HR 4.3, 95% CI 1.9 - 9.8, p < 0.001), PCLI-HR (HR 2.7, 95% CI 1.4 - 5.3, p = 0.004), and ISS-HR (HR 2.8, 95% CI 1.2 - 6.5, p = 0.015). There were 59 (FISH-HR), 424 (ISS-HR), and 507 (PCLI-HR) differentially expressed genes (q < 0.050 for all genes, volcano plots). PCLI-HR and FISH-HR demonstrated a predominance of transcriptional up-regulation while ISS-HR had a balanced gene expression profile with a similar number of genes being up- and down-regulated. The involved cellular pathways were different across the HR groups except for anti-apoptotic signaling (bar graphs). All HR groups had distinct gene expression profiles with no complete overlap between all HR groups. There were 71 genes with overlap between two HR groups (69 up-regulated, 2 down-regulated, Venn diagrams). The median GES was 97 (18 - 206, higher numbers indicating higher expression of up-regulated and lower numbers of down-regulated high-risk genes) in 559 patients treated on UAMS TT2 / TT3 (GSE24080). Tertiles of the GES were associated with event-free survival (HR 1.4, 95% CI 1.2 - 1.6, p < 0.001) and remained independently prognostic after adjusting for age, sex, and ISS stage (HR 1.3, 95% CI 1.1 - 1.5, p < 0.001). Conclusions: High-risk multiple myeloma remains associated with inferior overall survival, regardless of the used definition (structural or functional). The subtypes of high-risk disease have distinct gene expression profiles and involve different cellular pathways, providing important clues to the underlying biology. A 71 gene signature derived from the different high-risk subtypes was of prognostic significance in a clinical trial population after adjusting for known prognostic factors. Figure Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Stewart:Takeda: Consultancy; Seattle Genetics: Consultancy; Roche: Consultancy; Ono: Consultancy; Celgene: Consultancy, Research Funding; Ionis: Consultancy; Janssen: Consultancy, Research Funding; Oncopeptides: Consultancy; Amgen: Consultancy, Research Funding; Bristol Myers-Squibb: Consultancy. Bergsagel:Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Introduction: Several patient and disease biology characteristics that impact overall survival (OS) outcomes of patients with newly diagnosed multiple myeloma (NDMM) have been well described. However, several prior population-based registry studies in the US such as SEER and NCDB databases have demonstrated the negative prognostic impact of socio-economic (SE) factors such as low median household income based on US national census bureau data for zip code of residence as well as absence of marital support on the OS of NDMM patients. Whether such SE factors are independent of established host and disease biology related factors remains unknown due to the absence of detailed patient-level data in population-based cancer registries. Thus, we evaluated whether such SE factors independently affected the OS of NDMM patients in our institution when accounting for patient and disease biology related factors. Methods: We analyzed a retrospective cohort of consecutive NDMM patients seen at the Mayo Clinic from January 2005 to December 2015. Median household income for each patient's area of residence was estimated by matching their home zip code at diagnosis with data available through the US National Census Bureau. Median household income < $63,000 for a zip code were used to classify patients as having low income based on the National Cancer Database classification of the bottom three quartiles. Absence of marital support was considered in patients divorced, single or widowed at the time of diagnosis. Survival estimates were calculated using the Kaplan-Meier method. Patient and disease biology related factors taken into consideration included age, FISH cytogenetics, ISS stage and LDH levels. Survival estimates were compared between groups using the log-rank test. Multivariable adjusted proportional hazards regression models were fit for the association between known prognostic factors and OS. Results: A total of 2,621 MM patients were analyzed from the Mayo Clinic cohort of which 60% were male and the median age was 64 (22 - 96) years with 14% being 75 years of age or older. In this cohort, 541 (33%) patients had ISS 3 disease and 370 (22%) had high risk cytogenetics by FISH. The median OS based on estimated average household income was 65 months for the group of patients with low household income (N = 32%) and 80 months for the remainder (P = 0.001) (Fig 1A). The median OS based on marital support was 59 months for those without marital support at diagnosis (N = 21%) versus 76 months for remainder (P = 0.003) (Fig 1B). However, in a multivariable analysis that included the aforementioned SE factors and patient and disease biology characteristics , only age of 75 years or older (p < 0.001), the presence of high-risk FISH cytogenetics (p < 0.001), presence of ISS 3 disease (p < 0.001) and elevated LDH (p = 0.005) retained independent statistical significance in predicting for worse OS. Lower household income (p = 0.264) and absence of marital support (p = 0.054) were not independent predictors of worse OS. Conclusions: With the caveat of patient selection bias in a tertiary academic center, SE factors such as estimated average household income and marital support at diagnosis do not appear to impact OS of NDMM patients when considered in the context of traditional host and disease biology risk factors. These findings are in contrast to those suggested by population based registry studies; nevertheless, similar patient-level assessments should be considered in patient cohorts from non-tertiary medical centers as these results may likely be different. Disclosures Dispenzieri: Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Lacy:Celgene: Research Funding. Kapoor:Amgen: Research Funding; Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding. Russell:Imanis: Equity Ownership. Gertz:Medscape: Consultancy, Speakers Bureau; Research to Practice: Consultancy; Springer Publishing: Patents & Royalties; Ionis/Akcea: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Background: Lenalidomide maintenance therapy post-autologous stem cell transplantation (ASCT) is associated with improved progression-free survival (PFS) and possibly overall survival in multiple myeloma (MM). However, almost all patients do relapse as a result of residual multiple myeloma cells that remain after the high-dose chemotherapy. In the myeloma setting it has been found that the hedgehog (Hh) pathway is essential for maintaining a subset of tumor causing stem cells. LDE 225 (Sonidegib) is a potent selective oral bioavailable antagonist of Smoothened (SMO), a component of the Hh signaling pathway. In in vitro experiments, LDE225 treatment of myeloma cell lines resulted in a modest inhibition of cell proliferation at increasing doses. When LDE225 was combined with lenalidomide, a more than additive effect was observed in terms of cell proliferation, an effect that was more pronounced in the context of myeloma cell lines growing in co-culture with marrow derived stromal cells. These findings form the basis of evaluation of LDE 225 as a strategy to enhance the activity of lenalidomide in the post-transplant maintenance setting. The minimal residual state post SCT provides the most optimal situation for evaluation of a drug that is likely to work by inhibiting the tumor cells that escaped high dose therapy. Methods: Multiple myeloma patients without evidence of progression, who were 60 - 120 days after a single autologous stem cell transplant (SCT), performed within 1 year of diagnosis were eligible for the study. Maintenance therapy was started approximately 3 months after SCT. Treatment consisted of lenalidomide 10 mg days 1-21 and LDE225 400 mg days 1-28 in 28-day cycles for a total of 18 cycles. The goal of the study was to assess toxicity of this combination, complete response rate (CR) progression free survival (PFS) at 1 and 2 year and overall survival (OS). CR and PFS were estimated using an exact binomial distribution and Kaplan Meier curves respectively. Results: A total of 28 patients were accrued from Jan 2014 to Aug 2016, 1 patient canceled prior to treatment and 1 patient was deemed ineligible resulting in 26 evaluable pts for CR and PFS. The median age of all pts (n=26) was 60 years (range 43-69) and 50% were males. Seventy-three percent of patients reported one treatment regimen prior to SCT, while 27% reported 2 or more prior regimens. The other characteristics of the patient are summarized in Table 1. Twenty seven pts received at least one cycle of treatment and are evaluable for toxicities (AE). Patients were treated for a median of 12.5 (range 1-18) cycles. While 10 pts (38.5%) completed protocol treatment (18 cycles), the remaining 16 pts went off treatment due to AEs (6, 23%), disease progression (3, 11.5%), refusal of further treatment (3, 11.5%) and other reasons (4, 15.4%). A grade 3 or higher AE at least possibly attributed to either drug was seen in 63%. Grade 3+ hematologic toxicities were noted in 30%, with 7% neutropenia and 4% thrombocytopenia. Notable grade 2+ non-hematologic toxicities with more than 5% incidence were dysgeusia 22%, alopecia 11%, and anorexia 7%. Grade 3+ non-hematologic toxicities were fatigue, myalgia and arthralgia each at 7%. The CR rate in evaluable patients was 46% (5 CRs and 7 sCRs) with a 95% CI of 27% - 66%. CR rate improved from 31% to 46%. VGPR or better improved from 42% to 85%. The 24-month PFS (time from SCT to progression or death due to any cause) was 73% (95% CI: 57.9 - 92.3%) with a median time to censoring of 38 months. Conclusion: Lenalidomide in combination with LDE225 as posttransplant maintenance therapy was associated with some toxicity but manageable. The combination improved the depth of response after autologous stem cell transplant. Long-term follow-up is needed to determine overall survival. Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Gertz:Ionis: Honoraria; Alnylam: Honoraria; Prothena: Honoraria; Celgene: Honoraria; Spectrum: Honoraria, Research Funding; Janssen: Honoraria. Kapoor:Glaxo Smith Kline: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Sanofi: Consultancy, Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Russell:Imanis: Equity Ownership. Kumar:Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Sonidegib (LDE 225) is a selective oral bioavailable antagonist of Smoothened (SMO), a component of the hedgehog signaling pathway.

PURPOSE Observation is the current standard of care for smoldering multiple myeloma. We hypothesized that early intervention with lenalidomide could delay progression to symptomatic multiple myeloma. METHODS We conducted a randomized trial that assessed the efficacy of single-agent lenalidomide compared with observation in patients with intermediate- or high-risk smoldering multiple myeloma. Lenalidomide was administered orally at a dose of 25 mg on days 1 to 21 of a 28-day cycle. The primary end point was progression-free survival, with disease progression requiring the development of end-organ damage attributable to multiple myeloma and biochemical progression. RESULTS One hundred eighty-two patients were randomly assigned—92 patients to the lenalidomide arm and 90 to the observation arm. Median follow-up is 35 months. Response to therapy was observed in 50% (95% CI, 39% to 61%) of patients in the lenalidomide arm, with no responses in the observation arm. Progression-free survival was significantly longer with lenalidomide compared with observation (hazard ratio, 0.28; 95% CI, 0.12 to 0.62; P = .002). One-, 2-, and 3-year progression-free survival was 98%, 93%, and 91% for the lenalidomide arm versus 89%, 76%, and 66% for the observation arm, respectively. Only six deaths have been reported, two in the lenalidomide arm versus four in the observation arm (hazard ratio for death, 0.46; 95% CI, 0.08 to 2.53). Grade 3 or 4 nonhematologic adverse events occurred in 25 patients (28%) on lenalidomide. CONCLUSION Early intervention with lenalidomide in smoldering multiple myeloma significantly delays progression to symptomatic multiple myeloma and the development of end-organ damage.

241 Background: In a rapidly moving field, such as cancer immunotherapy, where immune checkpoint inhibitors (ICIs) are used across 14 different tumor types, patients may receive suboptimal treatment or even be harmed if information on toxicity is not readily translated for use in clinical practice. Every single systematic review and meta-analysis which attempted to summarize toxicity of immune checkpoint inhibitors (ICIs) quickly became outdated. A living systematic review, which is defined as a systematic review that is continually updated to incorporate relevant new evidence as it becomes available, is necessary in this situation. Methods: The process of creating a living systematic review started with the creation of a comprehensive search designed by a librarian experienced in systematic reviews in collaboration with the study’s principle investigator. Search was constantly updated every 3 months and evidence is synthesized in a series of steps (microtasks) using a combination of human and augmented intelligence. A complete infrastructure is being developed and it includes automated cumulative meta-analysis and an online reporting platform which will constantly update information for clinicians and patients in a live manner. Results: We screened 6746 studies during Sep 2018-March 2019 and identified 6746 studies and we were able to successfully maintain up-to-date toxicity estimates for immune mediated adverse events over this period while maintaining the rigor of a conventional systematic review. Eventually, we will integrate the steps of LSR into one, user-friendly, semi-automated format which can independently provide accurate estimates and feed into and support a living guidelines platform through shared Application Programing Interface (APIs). Conclusions: LSRs are feasible, efficient, and when fully developed can reduce redundancy and waste in medical research, improve the quality of evidence, reduce human effort and support living and dynamic guidelines to facilitate truly informed shared decision making.

80 Background: Several previous systematic reviews and meta-analyses have attempted to summarize toxicity of Immune Checkpoint inhibitors (ICIs). However, very soon after each one of these reviews has been published, it became outdated. ICIs are currently used in 14 different cancers and data is rapidly evolving from new clinical trials. A living Systematic review, which is defined as a systematic review that is continually updated to incorporate relevant new evidence as it becomes available, is necessary in this situations. Methods: In order to dynamically display content -- including textual data, tables, charts, and graphs – standard data formats and protocols were designed for various components of the systematic reviews carried out by researchers. Given these standardized formats, software was written to interpret this data and output the information in the appropriate format, such as a forest plot or data table. Finally, a dynamic interface that enables user inputs (such as which aspect of the meta-analysis to view) and displays the associated output was designed. The overall living Systematic Review infrastructure includes monthly literature searches, cumulative meta-analysis, and an online reporting platform. Results: We have developed a Living Systematic Review engine that can take in standardized data and reflect this data in an interactive, intuitive manner in the form of text, tables, and plots. This interface can also be manipulated via user input to organize and sort data tables or omit/highlight specific pieces of data. Conclusions: We have initiated the first living systematic review in immune-oncology that will be continuously updated, incorporating relevant new evidence as it becomes available, and will provide accurate and up to date toxicity estimates to support clinical decision making. The Living Systematic Review interface allows users to easily and intuitively access the most recent available clinical evidence on toxicity of ICIs.

AbstractRisk stratification of multiple myeloma (MM) at diagnosis is critical. We examined the ability of hematopoietic indices including mean corpuscular volume (MCV), hemoglobin (Hgb), and platelet (Plt) to predict outcomes. This was a retrospective study of patients treated at Mayo Clinic between January 2004 and April 2018. We incorporated three variables (Hgb < 10 g/dL, Plt < 150 × 109/L, and MCV > 96 fL), assigning a score of 1 to each. We identified 1540 newly diagnosed MM patients, of whom 707 (46%) had a score of 0, 513 (33%) had a score of 1, 260 (17%) had a score of 2, and 60 (4%) had a score of 3. The score risk stratified patients into four groups with differing survivals. The median PFS was 32.3 months for score 0, 24.8 months for score 1, 21.7 months for score 2, and 18.3 months for score 3, for P < .001. The median OS was 80.7 months for score 0, 59.9 months for score 1, 51.7 months for score 2, and 31.3 months for score 3, P < .0001. Predictors of OS on the multivariable analysis were age ≥ 65 (HR, 1.93; P < .0001), R‐ISS stage (1‐2 vs 3) (HR, 0.48; P < .0001), and hematopoietic score (0‐2 vs 3) (HR, 0.51; P = .006). A hematopoietic score can predict survival in newly diagnosed myeloma patients.

Abstract INTRODUCTION: Our group has demonstrated that MASS-FIX is a quick, inexpensive, and accurate means to diagnose and monitor the serum and urine of patients with plasma cell disorders. Screening can be done with a MALDI-TOF MS and samples reflexed to microflow liquid chromatography coupled with electrospray ionization (ESI) and Q-TOF MS (microLC-ESI-Q-TOF MS). Because this technique provides a mass/charge (m/z) for a given patient's monoclonal protein, this method can provide greater sensitivity and specificity to monitor for complete response (CR), especially in patients receiving therapeutic monoclonal antibodies. Our goal was to assess the performance of miRAMM in patients with AL who have been classified as complete response using conventional means. METHODS: We identified 77 patients with AL who had both documented CR by immunofixation (Seibia) of the serum (SIFE), urine IFE (UIFE), and serum free light chain (FLC; The Binding Site) and paired serum samples to test by MALDI-TOF and ESI-TOF. No urine samples were available to test. Paired serum samples from baseline and approximately one year post-therapy were immunoaffinity purified using nanobodies targeting kappa, lambda, alpha, gamma and mu as previously described. For the MALDI-TOF (Bruker Microflex, LT), a range of 9,000 to 32,000 m/z was acquired. The m/z distribution was then visually inspected for the presence of a peak that was distinct from the polyclonal background in both the M+1 and M+2 light chain mass ranges. For the ESI-TOF, spectra were also collected on an TripleTOF 5600 quadrupole time-of-flight mass spectrometer (ABSciex, Vaughan ON, CA) in ESI positive mode with a Turbo V dual ion source with an automated calibrant delivery system. TOF MS scans were acquired from m/z 600−2500 with an acquisition time of 100 ms. RESULTS: Median age of the cohort was 58 (range 42, 81). Fifty-eight percent were male. No test was 100% sensitive at baseline with positive results as follows: abnormal FLC ratio, 82%; positive SIFE, 70%; 73% positive UIFE; positive serum MASS-FIX, 71%; and ESI-TOF, 79% . There was light chain isotype agreement in all cases, except for 2 patients for whom the SIFE and the FLCr disagreed. Of the 56 patients with baseline positive MASS-FIX, there was evidence of the original monoclonal protein in 5 patients (see figure for example of spectra illustrating same m/z before and after therapy). Of the 63 patients who had baseline positive ESI-TOF, there was evidence of the original monoclonal protein in 8 patients. Small unrelated monoclonal proteins were seen both by SIFE and by mass spectrometry techniques. With the spectrometry techniques, however, these transient oligoclonal bands could be distinguished from the original monoclonal protein when they shared the same isotype based on the difference in m/z. DISCUSSION: At baseline, the MALDI was able to identify the baseline monoclonal protein in a comparable number of patients as SIFE, UIFE, and FLC. Approximately 10% of patients thought to be in CR using routine screening tests were found to have persistence of their original clone by MALDI and by ESI-TOF. Small post-therapy unrelated monoclonal proteins were also seen both by IFE and by MALDI, but either the presence of a different isotype or in the case of MALDI, a different m/z, made it clear that the monoclonal protein was not related to the original clone. The sensitivity of the assay will improve significantly when we formalize the introduction of free light chain magnetic beads to capture the serum FLCs. Routine use of MASS-FIX of the urine will also increase performance characteristics. Figure. Figure. Disclosures Dispenzieri: Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Gertz:Prothena: Honoraria; celgene: Consultancy; spectrum: Consultancy, Honoraria; Teva: Consultancy; Physicians Education Resource: Consultancy; annexon: Consultancy; Apellis: Consultancy; Alnylam: Honoraria; Medscape: Consultancy; Amgen: Consultancy; janssen: Consultancy; Research to Practice: Consultancy; Abbvie: Consultancy; Ionis: Honoraria. Kumar:Novartis: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Russell:Vyriad: Equity Ownership.

Abstract Background: Modern clinical practice places time restrictions on the amount of information and processing that can be done in a typical office visit. Meeting patient needs within the healthcare system is challenging, contributing to patient (pt) and clinician dissatisfaction and potential suboptimal outcomes. We developed an electronic point-of-care case management system for cancer patients. The system's goal is to obtain patient-reported quality of life (PROQOL) outcomes and provide clinicians with information regarding QOL issues to address. We tested this system in a prospective randomized study against usual care (UC). The primary objective was to determine if PROQOL system would improve mean QOL over time. Methods: Eligible pts were adults with multiple myeloma (MM) or light amyloidosis (AL), seen at Mayo Clinic. Pts were randomized 2:1 to PROQOL system or usual care. PROQOL system was offered prior to every visit. Pts select from various categories about their single biggest concern, and receive a printed list of actionable resources based on selected concern. Clinicians also receive the PROQOL results to review with pts. Providers and pts randomized to PROQOL completed a "was it worth it survey" (WIWI). An 8 item Linear Analogue Self-Assessment was used to assess QOL, the primary endpoint. Secondary endpoints included distribution of choices of most important concern and their relationship to demographic and clinical variables. The study was powered to detect a 0.5 standard deviation difference in QOL between groups. Results: There were 233 patients enrolled (171 MM, 62 AL) in this study between July 1, 2016 and April 17, 2018. Median age was 65 years (range 31-87), and 59% were male. Median time from diagnosis to study consent was 37 months (PROQOL 36.3 versus UC 39.6). Median follow up for all patients was 15 months (range: 0.7-22 months), and median follow up for PROQOL pts was 16 months and 14 months for UC pts (p=0.027). There were 25 pts that have died since enrollment and 208 alive. No statistical significant difference in QOL between PROQOL and UC (median QOL 7 vs 7, p=0.75). The most prevalent main concerns selected were Physical Health (37%) and Cancer and Diagnosis (27%), the pattern remained even when pts were given the option to pick a second major concern 26% and 20% respectively. No other concern was listed more than 8% at baseline. All category selections and percentages are shown in the Figure. The average time to complete the instrument was 6 minutes. Pts found the PROQOL system was worth their time (75%), they would choose it again (87%) and recommend it to others (82%). Eighty-two percent of clinicians did not think the PROQOL tool negatively impacted their practice and 75% believed they may see improvement in pt wellbeing. Discussion: The PROQOL system was well received by pts and clinicians but did not improve QOL relative to UC in this study. The PROQOL demonstrates that majority of patients strongly desire more information regarding ongoing therapy, clinical trials, prognosis and toxicity. Further investigation is needed to understand whether communication is limited by time or mechanism of information delivery, such as verbal or written, or whether it should be undertaken in a separate allied health care visit. Figure. Figure. Disclosures Gertz: spectrum: Consultancy, Honoraria; Abbvie: Consultancy; Research to Practice: Consultancy; annexon: Consultancy; Medscape: Consultancy; Physicians Education Resource: Consultancy; Amgen: Consultancy; janssen: Consultancy; Alnylam: Honoraria; Teva: Consultancy; Apellis: Consultancy; Ionis: Honoraria; celgene: Consultancy; Prothena: Honoraria. Kumar:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Lacy:Celgene: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.