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Introduction Minimal residual disease (MRD) status at day 100 following autologous stem-cell transplant (ASCT) in multiple myeloma (MM) patients is an important determinant of prognosis. Bone marrow (BM) based assays, i.e. next-generation flow cytometry (NGF) or next-generation sequencing (NGS) that are currently used in determining MRD are vulnerable to sampling biases due to patchy marrow involvement and extramedullary disease. BM examination alone may lead to false-negative results. MRD assessment through newer, more sensitive peripheral blood based methodologies such as mass spectrometry (MS) can potentially overcome the limitations associated with BM based assays. At our institution, traditional immunofixation electrophoresis (IFE) has been replaced by a MS method termed Mass-Fix which utilizes the unique light chain mass associated with each patient's monoclonal protein to monitor disease over time. In this study, we assessed the prognostic impact of serum Mass-Fix MRD status in MM patients who were MRD negative by NGF around day 100 post-ASCT. Methods Patients with MM who underwent ASCT between 01/01/2015 and 12/31/2018 at Mayo Clinic, Rochester were included in this study provided they had attained post ASCT day 100 complete response (CR) by IMWG 2016 criteria and MRD- state as assessed by BM based NGF, utilizing 2 eight-color tubes (total 10 colors), with a minimum sensitivity 10-5. Presence of non-secretory MM and unavailability of pre-ASCT serum samples or serum IFE results were important exclusion criteria. Peripheral blood samples drawn concurrently with the BM assessment were evaluated by Mass-Fix as described previously (Mills et al., Clin. Chem, 2016). The isotype and mass of the M-protein light chain (LC) obtained by Mass-Fix were compared to the pre-ASCT M-protein LC and/or IFE isotype. Patients with the following genetic alterations: deletion 17p, translocation (4;14), (14;16), t(14;20) and1q gain/amplification and were considered high risk. All time-to event analyses were performed on JMP 14.1.0 from the time of ASCT using the Kaplan-Meier method. Results Sixty-two patients with MM (57 newly diagnosed and 5 relapsed/refractory) who underwent ASCT and were MRD- by BM based NGF around day 100 (range: day 60-120) were included in the study. Median age at ASCT was 61 (range: 40-76) years and 61% were males. Thirty (48%) patients had IgG MM, 15 (25%) patients had IgA MM and 17 (27%) patients had light chain only disease. Forty-one (66%) patients received bortezomib, lenalidomide and dexamethasone (VRD) as induction regimen. Median time from diagnosis to ASCT was 6 months (IQ range: 4.7-7.2). Pre-ASCT fluorescence in- situ hybridization data were available on 47 (76%) patients; 23 (49%) were high risk. Of 62 patients, all of whom were day 100 MRD- by NGF, 36 (58%) patients had Mass-Fix identified MRD (MRD+). MRD positivity by Mass-Fix around day 100 was observed in 70% of patients with high risk MM versus 71% of patients with standard risk MM, p=0.9. The median follow-up was 18 months (95%CI: 14-21); 19 months (95%CI: 15-21) for patients who were MRD+ by Mass-Fix versus 17 months (95%CI: 12-21) for those who were MRD- by Mass-Fix at day ~100, p=0.5. Of 57 (92%) patients who received post ASCT maintenance therapy, 32 (89%) were MRD+ and 25 (96%) were MRD- by Mass-Fix, p=0.5. Eighty-seven percent of patients with IgG MM had MRD+ status by Mass-Fix at day~100. By contrast, only 33% and 30% of patients with IgA MM and light chain MM, respectively, had MRD+ status at day 100; p<0.0001. This suggests that IgG half-life which is longer than that of IgA or free light chains may affect the day 100 MRD status. At 18 months, 76% and 93% of patients, who were MRD+ and MRD- , respectively by Mass-Fix were alive and free from disease progression, p=0.03 (Table 1, Figure 1a). At 18 months after ASCT, none of the patients who were MRD- by Mass-Fix required salvage treatment following ASCT while 25% of patients who were MRD+ by Mass-Fix required next line of therapy due to disease progression, p=0.05 (Table 1, Figure1b). Conclusion Our data suggest that outcomes [progression free survival (PFS) and time-to-next therapy (TTNT)] of patients with MM who are in CR, and have achieved MRD- state by BM NGF post ASCT, can be adversely impacted if there is concurrent evidence of serum monoclonal protein by Mass-Fix, thereby demonstrating incremental prognostic value of this sensitive assay in clinical practice. Disclosures Murray: The Binding Site: Patents & Royalties: US Patent Rights on Mass Spectroscopy Licensing agreement with The Binding Site, Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Dasari:The Binding Site: Patents & Royalties: US Patent Rights on Mass Spectroscopy Licensing agreement with The Binding Site, Research Funding. Gertz:Teva: Speakers Bureau; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Celgene: Consultancy; Research to Practice: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Physicians Education Resource: Consultancy; Medscape: Consultancy, Speakers Bureau; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Ionis/Akcea: Consultancy; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials. Dingli:Karyopharm: Research Funding; Millenium: Consultancy; Rigel: Consultancy; Janssen: Consultancy; alexion: Consultancy. Lacy:Celgene: Research Funding. Leung:Omeros: 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; Takeda: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Kapoor:Takeda: Honoraria, Research Funding; Janssen: Research Funding; Celgene: Honoraria; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Glaxo Smith Kline: Research Funding; Cellectar: Consultancy.

Background: The overall participation of cancer patients in interventional clinical trials in the United States remains very low, with ~5% of patients being enrolled in clinical trials nationwide. The outcomes of patients with MM have improved significantly over the past decade, but available data suggest that the participation rates for patients with MM is comparable to other cancers. The drivers of participation and the potential impact of clinical trial participation have not been systematically studied in MM. Patients and Methods: We identified 228 patients who were enrolled into clinical trials for initial therapy of newly diagnosed MM between 2004 and 2018, and 4 controls for each of these patients. Controls were patients with NDMM, who were diagnosed closest in time to the index patients and did not participate in an interventional treatment trial. Various baseline characteristics as well as overall survival were compared between the two groups. Results: The baseline characteristics of the two groups are as shown in the Table. Patients who entered clinical trials were more likely to be female, resided closer to the clinic, and were more likely to have a prior history of MGUS. They were more likely to have higher ISS Stage, and a higher serum LDH, but there was no difference in the FISH risk status. Other indices of disease burden such as lower hemoglobin and platelets, higher serum creatinine were all seen more often in the control group, but may have been influenced by the trial entry criteria. Looking at the outcomes, the overall survival was longer among those enrolled into clinical trials compared to those who did not [median 103 (95% CI; 86, 136) vs. 63 (95% CI; 53, 69) months, p<0.001 (Figure). Conclusions: The current study provides important clues regarding demographic determinants of trial participation and disease biology related features that reflect likelihood of trial participation. Overall survival was significantly longer among the trial participants, which likely represent a mix of reasons including baseline status of patients, intensity of monitoring and efficacy of novel treatment approaches. Table Disclosures Kapoor: Janssen: Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Glaxo Smith Kline: Research Funding; Takeda: Honoraria, Research Funding. Dispenzieri:Alnylam: Research Funding; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Akcea: Consultancy; Intellia: Consultancy. 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; alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy. Leung:Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees. Russell:Imanis: Equity Ownership. Kumar:Takeda: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Introduction: There is a paucity of randomized trials to guide therapy for relapsed AL amyloidosis with treatment regimens generally extrapolated from experience in multiple myeloma. Methods: We conducted a retrospective review of patients who relapsed after receiving autologous stem cell transplant at Mayo Clinic. Patients treated for first relapse between January 2004 and December 2018 were included. Results: Three hundred and twenty-one patients were seen for relapsed AL amyloidosis post ASCT during the study period. Baseline characteristics were typical for a cohort with AL amyloidosis and are listed in Table1. 39% received therapy prior to transplant, conditioning in the majority (75%) was melphalan 200mg/m2. The median progression free survival from transplant (PFS1) was 30.7 months. Of the 321 patients 294 received treatment for relapsed disease. We categorized treatment regimens according to commonly used combinations and drug classes to further analyze outcomes. 34 patients were excluded from this analysis as they either proceeded directly to second ASCT (n=10) or received an atypical regimen not commonly considered for AL amyloidosis (n=24). Five categories of therapy regimens were identified, thalidomide based (n=110), melphalan plus steroids (n=31), 2nd generation immunomodulatory (IMiD) drug +/- alkylator (n=76), proteasome inhibitor (PI) +/- alkylator (n=116), PI plus IMiD (n=16), or daratumumab based (n=9). Disease and treatment characteristics for patients treated with these regimens are listed in Table 2. Patients treated with thalidomide had the shortest PFS1 (17.7 months) but PFS1 was similar for those treated with melphalan plus steroids, PI+IMiD and 2nd generation IMiDs (25.5, 24.3 and 25.6 months respectively). Patients treated with a PI +/- alkylator and daratumumab based regimen had the longest PFS1 (36.7 and 41.9 months respectively). The median duration of therapy was longer in patients treated with a 2nd generation IMiD or daratumumab based regimen (10.2, 12, 6.1, 5.5, 6.2 and 5.9 months for Dara based, 2nd generation IMiD, PI+/- alkylator, PI+IMiD, melphalan plus steroids and thalidomide based respectively). Hematologic response rate was lowest in those treated with melphalan plus steroids or thalidomide based regimens (44% and 55% respectively) and highest for patients treated with a PI+/- alkylator, (Figure 1). Progression free survival from relapsed therapy (PFS2) was longest amongst patients treated with daratumumab based regimens, PI +/- alkylator and 2nd generation IMiDs (not reached, 29.9 and 26.7 months respectively), Figure 2A. Overall survival from time of relapsed therapy favored patients treated with daratumumab based regimens, 2nd generation IMiDs and PI +/- alkylator, Figure 2b). Conclusion: A second generation IMiD based regimen or PI +/- alkylator produce high response rates and prolonged progression free and overall survival for relapsed AL amyloidosis. Patients treated with daratumumab based regimens and those treated with a PI plus IMiD also appear to do well, although numbers were low in our study. Patients treated with melphalan plus steroids or thalidomide based combinations have inferior outcomes and these regimens should be avoided. Disclosures Dispenzieri: Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kapoor:Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Appellis: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Annexon: Consultancy. OffLabel Disclosure: Daratumumab off label use for AL amyloidosis.

Introduction: Daratumumab is a human immunoglobulin (IgG-κ) that targets CD38 abundantly expressed on plasma cells. Data is emerging to show its efficacy as part of induction therapy for newly diagnosed multiple myeloma (MM) patients. Hematopoietic stem cells have been shown to express CD38 on the cell surface and therefore during mobilization, there is a theoretical risk of circulating daratumumab binding to and having downstream effects on these cells. Methods: We conducted a retrospective review of MM patients treated with daratumumab prior to stem cell collection and autologous stem cell transplant (ASCT) to identify any effects daratumumab therapy may have on the efficacy of the stem cells in bone marrow recovery. The study was conducted at Mayo Clinic Rochester from February 2018 to May 2019. Granulocyte colony-stimulating factor was the preferred agent used for stem cell mobilization and plerixafor was added in a demand-adapted fashion. All patients received melphalan infused at day -1 before their ASCT and the decision about dosing (200mg/m2 vs 140mg/m2) was at the physicians' discretion. Neutrophil engraftment was defined as the first date of three consecutive neutrophil counts >0.5 x 10^9/L and platelet engraftment was defined as the first date of three consecutive platelet counts >50 x 10^9/L in the absence of platelet transfusion in the preceding 7 days. Results: We identified 12 patients who received daratumumab as part of their first induction regimen (daratumumab cohort) and compared them to 129 patients who did not receive daratumumab prior to stem cell mobilization and transplant during the study period (no daratumumab cohort). Of the daratumumab cohort, 11 patients received daratumumab, ixazomib, lenalidomide, and dexamethasone and one received daratumumab, cyclophosphamide, bortezomib and dexamethasone. No differences were noted in terms of melphalan dose or the number of CD34+ stem cell infused. The median time from the last dose of daratumumab to stem cell collection was 3.9 weeks. In patients receiving daratumumab, the median time for neutrophil engraftment was three days longer compared with those who did not receive daratumumab (median of 19 days vs. 16 days, P=0.017) (Figure 1, A). Median platelet engraftment was delayed by one day, although this was not statistically significant (median of 18 days vs. 17 days, p=0.12) (Figure 1, B). A total of 6 patients (50%) from the daratumumab cohort and 52 (40%) from the no daratumumab cohort required hospital admission. Of these admissions, there was no difference between the two groups in rates of admission for fever (50% in the daratumumab group vs. 42% in the no daratumumab group, P=0.7). Conclusion: Our case series provides the first report of daratumumab delaying engraftment post transplant in myeloma patients receiving it prior to stem cell collection. A better characterization of this phenomenon is important given the increasing use of daratumumab as front line therapy prior to ASCT in patients with myeloma. Disclosures Gertz: Prothena: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Spectrum: Honoraria, Research Funding; Alnylam: Honoraria; Ionis: Honoraria. Lacy:Celgene: Research Funding. Kapoor:Sanofi: Consultancy, Research Funding; Glaxo Smith Kline: Research Funding; Cellectar: Consultancy; Janssen: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Celgene: Honoraria. Dispenzieri:Alnylam: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Introduction: Risk stratification of patients with light chain (AL) amyloidosis at diagnosis is invaluable. Currently, the Mayo 2012 staging system is mainly used to risk-stratify patients. We evaluated the role of increased mean corpuscular volume (MCV) at diagnosis in predicting survival. Methods: We conducted a retrospective study of patients with newly diagnosed AL amyloidosis seen at Mayo Clinic, Rochester between January 2006 through December 2015. The diagnosis of AL was confirmed with biopsy and the determination of organ involvement was according to consensus criteria. Staging was done according to the Mayo 2012 staging system and patients with stage III/IV were considered to have advanced stage disease. Patient and disease factors were compared for categorical and continuous variables using the χ2 and the Wilcoxon signed rank tests, respectively. Overall survival (OS) was defined as the time from diagnosis to death of any cause. Survival analysis was done using the Kaplan-Meier method. Results: A total of 1064 patients were identified and were divided into two groups: those with an MCV ≥ 96 fl (Elevated MCV, n=180) and those with an MCV <96 fl (Low MCV, n=884). The median age at diagnosis for the whole cohort was 64, with an interquartile range (IQR) of 57-71. Overall, 222 (23%) had Mayo 2012 stage 1, 199 (21%) had stage 2, 239 (25%) had stage 3, and 290 (31%) had stage 4 disease. Patients with an elevated MCV were more likely to be more than 65 years old compared to patients with a low MCV (61% vs. 44%, p<0.0001). They were also likely to have an advanced Mayo 2012 stage (68% vs. 53%, P=0.0008). The median OS was significantly lower in patients with an elevated MCV compared to patients with a low MCV (median PFS 13 months vs. 41 month, respectively, P<0.0001)(Figure 1). On a univariable analysis, predictors of OS were advanced Mayo 2012 stage (RR 3.26, P<0.001) and MCV ≥ 96 (RR 1.6, P<0.0001). On the multivariable analysis, both variables remained predictors of OS [advanced Mayo 2012 stage (RR 3.19, P<0.001) and MCV ≥ 96 (RR 1.3, P=0.016)]. Conclusion: The median OS was shorter by 28 months in newly diagnosed AL amyloidosis patients with an MCV ≥ 96 compared to patients with an MCV<96. An elevated MCV was predictive of shorter survival, independent of the Mayo Stage. This variable is easily available, measured in all newly diagnosed patients, and provides valuable prognostic information for the treating physician. Disclosures Dispenzieri: Intellia: Consultancy; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Alnylam: Research Funding; Celgene: Research Funding; Akcea: Consultancy. Lacy:Celgene: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees. Kapoor:Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Janssen: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Glaxo Smith Kline: Research Funding. Gertz:i3Health: Other: Development of educational programs and materials; Alnylam: Consultancy; Celgene: Consultancy; Appellis: Consultancy; Teva: Speakers Bureau; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Ionis/Akcea: Consultancy; Prothena Biosciences Inc: Consultancy; Janssen: Consultancy; International Waldenstrom Foundation: Research Funding; Proclara: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; DAVA oncology: Speakers Bureau. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

Introduction: Vitamin D deficiency is common, with 25-50% of the population having levels below the optimal range (<20 ng/mL). Aside from its role in maintaining serum calcium and skeletal homeostasis, vitamin D has been shown to play an important role in regulation of differentiation, proliferation, apoptosis, metastatic potential and angiogenesis in a variety of malignancies. Low serum 25(OH)D levels have been associated with a worse prognosis in several malignancies, including colorectal and breast cancer, chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Almost no data have been reported on vitamin D levels in light chain (AL) amyloidosis. We therefore measured vitamin D levels among AL patients and correlated levels at presentation to explore if vitamin D deficiency has any effect or association in this disease. Methods: Stored serum samples from 90 patients with newly diagnosed AL amyloidosis were obtained for vitamin D studies, which included 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin D binding protein (DBP). All vitamin D measurements were made by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total 25(OH)D and 1,25(OH)2D was assessed as the additive sum of the 25(OH)D2/25(OH)D3 and 1,25(OH)2D2/1,25(OH)2D3 components, respectively. Clinical data was extracted from the electronic medical records. All calculations were made using JMP software (SAS, Cary, NC). Results: All patients were seen between June 2004 and September 2013. Median age was 63 [IQR 57-70]. Heart, kidney, nerve, liver and gastrointestinal amyloidosis was seen in 80%, 60%, 19%, 17% and 13% of patients, respectively. The median dFLC and bone marrow plasma cells were 28 (IQR 12-84) mg/dL and 10% (IQR 5-20%), respectively. The median serum 25(OH)D level was 20 ng/mL (IQR 10-29; normal >20 ng/mL), while the median serum level of 1,25(OH)2D was 23 pg/mL (IQR 14-37; normal 16-64 pg/mL for men; 16-78 pg/mL for women). 25(OH)D levels <20 ng/mL were strongly associated with renal involvement (84% renal involvement vs 42% of renal involvement for levels ≥20 ng/dL, P<0.001; Table). No other association with organ involvement was seen. Among all patients, heavy proteinuria (>5 gr/24-h) was strongly associated with low 25(OH)D, (P<0.001, Table). A weaker association was seen between 25(OH)D levels and estimated glomerular filtration rate (eGFR) (P=0.06). Seventy-eight percent of patients with 1,25(OH)2D levels below 20 pg/mL had renal involvement versus 48% in those with levels above 20 pg/mL (P=0.01). While heavy proteinuria was associated with 1,25(OH)2D (P=0.008), the association was stronger for eGFR, as no patient with an eGFR <30 ml/min/1.73 m2 had a 1,25(OH)2D level above 20 pg/mL (P<0.001). An association between vitamin D levels and low serum albumin was also seen, mainly in relation to 25(OH)D (Table). The median level of serum DBP was 58 μg/mL (IQR 36 - 120 μg/mL), significantly lower than the normal range (168-367 μg/mL). Low levels of 25(OH)D or 1,25(OH)2D were not associated with lower DBP levels. Surprisingly, patients with renal involvement had higher levels of DBP versus those without renal involvement (median 70.9 vs 48 μg/mL; P=0.03), although median levels were below normal in both groups. FISH data was available in 47 of patients (52%). Patients with 25(OH)D levels <20 ng/dL were less likely to harbor t(11;14) versus patients with 25(OH)D levels above this threshold (26% vs 64%, respectively; P=0.0095). A similar, but less significant association was seen between 1,25(OH)2D levels at a 20 pg/mL threshold and t(11;14) (35% vs 59%, P=0.09). Other associations between vitamin D and FISH abnormalities were not seen. Conclusions: Hypovitaminosis D is common among AL amyloidosis patients with renal involvement. In the general cohort, heavy proteinuria, reduced eGFR and low serum albumin were all associated with low circulating vitamin D levels. Although the majority of AL patients had low levels of DBP, urinary loss of DBP does not explain the low levels of vitamin D. Hypovitaminosis D is associated with non-t(11;14) disease, a finding which warrants further exploration. Disclosures Dispenzieri: Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:Rigel: Consultancy; Karyopharm: Research Funding; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Kapoor:Cellectar: Consultancy; Celgene: Honoraria; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding; Glaxo Smith Kline: Research Funding. Leung:Omeros: 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; Takeda: Research Funding. Russell:Imanis: Equity Ownership. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Gertz:Ionis/Akcea: Consultancy; Alnylam: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Annexon: Consultancy; Prothena Biosciences Inc: Consultancy; Spectrum: Consultancy, Research Funding.

Background: POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. The combination of a proteasome inhibitor, an IMiD and corticosteroid is known to be highly effective among patients with myeloma. Methods: We conducted a pilot using a 28-day oral regimen of ixazomib (4 mg days 1, 8, 15), lenalidomide (25 mg days 1-21), and dexamethasone (20 mg days 1, 8, 15, 22). Aspirin and acyclovir were used for prophylaxis. Eligibility included a diagnosis of POEMS syndrome, a plasma VEGF 2x normal, a PS < 3. There were two groups [gp] (intended enrollment 15 per gp): Gp 1, 3 cycles for pts destined for high-dose chemotherapy with stem cell transplant; Gp 2, 13 cycles for patients (pts) who had relapsed or refractory disease. Primary endpoint was VEGF complete response (CR=normalization) after 3 cycles. Secondary endpoints included safety, hematologic response, and overall survival at 3 and 12 months. Other domains including PET response (50% reduction in sum of SUVmax from baseline), clinical responses including neurologic response were also studied. Neurologic assessments were done using the modified neurological impairment score (mNiS+7POEMS), the overall neuropathy limitation scale, and the polyneuropathy disability score. To date, 13 pts enrolled since 10/31/2016-4 to Gp 1 and 9 to Gp 2. 11 pts were analyzed (2 dropped out before receiving any therapy). Data were frozen as of 07/15/2019. Results: Median age was 55; 73% were male. Of the evaluable patients, three were newly diagnosed (Gp 1), and 8 had relapsed or refractory disease (Gp 2). 72% met primary endpoint of VEGF CR (Table). At 3 months, the following improvements were seen: VEGF, 10/11; hematologic, 1/3; PET 1/3; neurologic impairment score, 3/11. By 12-months according to the modified nerve impairment scale, 3/6 had achieved objective improvement and 2/6 stable disease. With a median follow-up of 16 months, 2 patients have died of progressive disease and another patient progressed on therapy (Gp 2) with an extravascular leak progression. 27% of patients had grade 3+hematologic AE; 81% had grade 3-4 non-hematologic AE. These included: rash, respiratory infection, diarrhea, and hypotension in 2 each; atrial fibrillation, edema, dyspnea, and thromboembolism in 1 each. 5 pts had non-objective worsening of their neuropathy. Conclusions: These preliminary results suggest that Ixa-Len-Dex is an effective and tolerable regimen for patients with POEMS syndrome. Longer follow-up will be important to determine durability of this approach and for neurologic assessment given the slow rate of remyelination. Figure Disclosures Dispenzieri: Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Kapoor:Cellectar: Consultancy; Janssen: Research Funding; Glaxo Smith Kline: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Amgen: Research Funding. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Dingli:alexion: Consultancy; Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Proclara: Membership on an entity's Board of Directors or advisory committees; Springer Publishing: Patents & Royalties; Research to Practice: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; DAVA oncology: Speakers Bureau; Pharmacyclics: 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; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau. OffLabel Disclosure: No drugs approved for POEMS syndrome. Ixazomib, lenalidomide and dexamethasone

Background: A variety of risk factors have been described in multiple myeloma and current risk assessment incorporates ISS stage with specific FISH results and serum LDH (R-ISS). However, this model does not include all the current abnormalities described as prognostic for survival in multiple myeloma. Importantly, the impact of many of these high-risk abnormalities are not uniform. We examined if we can better integrate FISH results into a risk assessment tool to better predict the outcomes of newly diagnosed MM. Patients and methods: We studied a cohort of 1316 patients with FISH done within 6 months of diagnosis of MM, in whom results for commonly observed abnormalities were available. We specifically examined the individual impact of common translocations involving chromosome 14, MYC rearrangements, chromosome 1q gain (single or multiple duplication) and del13q/monosomy 13. A risk assessment system was developed, weighting each abnormality according to their Risk Ratio and integrating ISS stage and serum LDH into the final model construction. Overall survival was calculated from diagnosis, with those alive at last follow up being censored. Results: We first examined the impact of each of the above FISH abnormalities: 1) high risk translocations [t(4;14), t(14;16), or t(14,20)], 2) trisomies, 3) t(11;14), 4) MYCrearrangements, 5) del13q/monosomy 13, and 6) 1q gain . Each of the abnormalities, except for t(11;14), was prognostic for survival (Table 1 with the risk ratios). For 1q gain, the median OS was NR, 105 mos and 79 mos respectively for no abnormality, duplication of 1 copy and duplication of multiple copies, (p<0.001). On multivariate analysis, t(11;14) and trisomies were no longer prognostic for overall survival (Table 1). The cumulative impact of abnormalities demonstrated worsening survival in the presence of increasing numbers of abnormalities (Figure 1). Including ISS stage 3 and LDH > ULN as additional variables for prognostication indicated both were individually prognostic for OS. In a multivariate analysis, including these two and FISH abnormalities, 1q gain and LDH were not independently prognostic. The final model consisted of HR translocations, MYCrearrangements, del17p/monosomy 17, del13q/monosomy 13, and ISS stage 3. Each of these variables was weighted using their risk ratio and a composite score was developed using 998 patients for whom all variables were available (range: 0-7.9; median 1.8). Three patient groups were characterized: group 1 (0; 32%), group 2 (1-4; 58%) and group 3 (>4; 10%) with a median OS of 53 mos, 106 mos, and NR, respectively, p <0.001 (Figure 2). Conclusion: Using the most relevant FISH and laboratory factors, in a large cohort of patients, we refined the current system to develop a risk stratification system that predicts survival in patients with newly diagnosed MM treated with contemporary treatment regimens. This needs validation in future studies. Disclosures Kumar: Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. Gertz:International Waldenstrom Foundation: Research Funding; Annexon: Consultancy; Medscape: Consultancy, Speakers Bureau; Amyloidosis Foundation: Research Funding; Abbvie: Other: personal fees for Data Safety Monitoring board; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Physicians Education Resource: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Appellis: Consultancy; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Amgen: Consultancy. Dispenzieri:Akcea: Consultancy; Janssen: Consultancy; Intellia: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kapoor:Celgene: Honoraria; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Smith Kline: Research Funding; Takeda: Honoraria, Research Funding; Amgen: Research Funding; Cellectar: Consultancy. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees. Bergsagel:Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy.

Introduction: Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor plus low dose dexamethasone (Sel-dex) was recently approved in the United States based on data from the STORM study wherein, Sel-dex induced an overall response rate (ORR) of 26.2% in patients with penta-exposed, triple-class refractory multiple myeloma. The presence of high-risk cytogenetic abnormalities is known to have a poor prognosis in multiple myeloma, with transient responses. We performed post-hoc analyses to determine the outcomes in patients with relapsed/refractory myeloma treated with Sel-dex based on the baseline cytogenetic abnormalities. Methods: STORM was a phase 2b, open-label study which enrolled patients with relapsed and refractory myeloma. Selinexor 80 mg in combination with dexamethasone 20 mg was administered orally, twice weekly. The primary endpoint was ORR. For this analysis, we pooled 78 patients (48 quad-refractory and 30 penta-refractory) from STORM, part 1 and 122 patients (penta-exposed and triple class refractory) from STORM, part 2 to compare outcomes between high-risk and standard risk cytogenetics groups. High-risk cytogenetics was defined as having at least 1 of the following abnormalities by fluorescence in-situ hybridization (FISH) at baseline: del(17p), t(4;14), t(14;16), and gain(1q) in >5% of screened plasma cells. The FISH analyses were performed at a central laboratory and used to assess cytogenetic risk status. Results: Of the 200 patients, 122 (61%) had high-risk disease (del(17p): 36%, t(4;14): 18%, t(14;16): 5%, and gain(1q): 36%). The ORR in high-risk patients was 20.5% (very good partial response [VGPR)]: 5.7% and partial response [PR]: 14.8%) and the ORR was 29.5 % (complete response [CR]: 2.6%, VGPR: 3.8%, and PR: 23.1%) in standard-risk patients. The clinical benefit rate (CBR) was 35.2% in high-risk patients compared with 38.5% in standard-risk patients. Median duration of clinical benefit (DOCB) was 4.4 and 6.2 months in the high-risk and standard-risk patients respectively. Median progression-free survival (PFS) was 3.8 and 4.2 months and overall survival (OS) was 8.6 and 9.4 months in the high-risk and standard-risk patients, respectively. Efficacy by specific cytogenetic abnormality is presented in Table 1 below (Due to the small sample size (n=11), data for the t(14;16) subgroup are not presented separately). Conclusions: Sel-dex demonstrated a similar CBR in patients with high risk and standard risk disease and preserved clinical benefit in heavily pre-treated patients who had rapidly proliferative disease and high-risk cytogenetics at baseline. The benefit was maintained across cytogenetic risk subgroups with a higher ORR in the t(4;14) and gain(1q) subgroups. The DOR and OS was similar across all the subgroups. These analyses support the use of Sel-dex in patients with high-risk cytogenetics and warrant further evaluation of selinexor in combination with other anti-myeloma therapies in high-risk disease. Disclosures Nooka: GSK: Honoraria, Other: advisory board participation; Amgen: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation. Yee:Adaptive: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Huff:Karyopharm, Sanofi, MiDiagnostics: Consultancy; Member of Safety Monitoring Board for Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Vogl:Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Active Biotech: Consultancy. Chari:Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Oncoceutics: Research Funding. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; alexion: Consultancy; Janssen: Consultancy. Lonial:Genentech: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; BMS: Consultancy; Janssen: Consultancy, Research Funding; GSK: Consultancy; Celgene Corporation: Consultancy, Research Funding. Dimopoulos:Sanofi Oncology: Research Funding. Vij:Takeda: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Genentech: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Tuchman:Karyopharm: Honoraria; Celgene: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding; Merck: Research Funding; Prothena: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Alnylam: Honoraria, Research Funding. Biran:Bristol Meyers Squibb: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Siegel:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Richardson:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: 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; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Liu:Karyopharm Therapeutics: Employment, Equity Ownership. Joshi:Karyopharm Therapeutics: Employment, Equity Ownership. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Shacham:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kauffman:Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jagannath:Medicom: Speakers Bureau; Multiple Myeloma Research Foundation: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Merck: Consultancy.

Background: Combinations of alkylating agents with proteasome inhibitors have demonstrated efficacy in newly diagnosed and relapsed multiple myeloma (MM), with melphalan or cyclophosphamide combinations being some of the commonly used regimens for initial treatment of MM. Ixazomib (Ixa) is an oral proteasome inhibitor that is approved for use in combination with lenalidomide for patients with relapsed MM. We examined if Ixa can be effectively combined with cyclophosphamide (Ctx) in order to develop a less expensive, all oral regimen for patients with relapsed MM. Patients and Methods: Patients with relapsed MM, who were proteasome inhibitor naïve OR have received less than 6 cycles of therapy with bortezomib and had a better than PR with no progression at the time of discontinuation, were enrolled. The primary objective was to determine overall response rate (ORR). Treatment consisted of Ixa 4mg PO days 1, 8, 15; Ctx 300 mg/m2 PO days 1, 8, 15, 22 and dexamethasone (Dex) 40 mg PO weekly in a 28-day cycle. Overall, 37 patients were accrued; data on 33 eligible patients were available for analysis as of July 18, 2019. Results: The median age was 71 (48-89), 61% were male and the median duration from diagnosis was 46 months (mos). Median number of prior lines of therapy was 4 (range 1-5), 76%, 42% and 67% respectively had a prior IMiD, proteasome inhibitor or stem cell transplant, respectively. At data cutoff, 22 (67%) had progressed, 4 (12%) had died and the median follow up of those alive was 21.3 mos. Fourteen patients are still receiving treatment, with median of 8.5 cycles. Most common reason for treatment discontinuation was disease progression (10 pts; 53%). The ORR was 60% including 6% CR and 24% VGPR. The median event free survival was 11.3 mos (95%CI: 9.0 - 26.8). Overall, 401 cycles have been administered across the study, with dose modifications/ hold required for Ixa, Ctx, and Dex in 9 (27%), 14 (42%), and 22 (67%) patients respectively, the most common reason being hematologic toxicity. A grade 3 or higher adverse event at least possibly attributed to the study drugs was seen in 77% of patients, hematologic in 67% and non-hematologic in 30%. (Table 1) The most commonly observed hematologic toxicities included thrombocytopenia, neutropenia, lymphopenia and anemia; for non-hematologic was nausea, diarrhea, peripheral neuropathy toxicity and fatigue. Conclusions: The combination of Ixa, Ctx and Dex (ICd) offers a convenient, all oral regimen for treatment of relapsed disease not refractory to proteasome inhibitors. The regimen has good efficacy in this group f heavily pretreated patients, with an acceptable toxicity profile. Disclosures Lacy: Celgene: Research Funding. Gertz:Ionis: Honoraria; Spectrum: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Prothena: Honoraria; Alnylam: Honoraria. Ailawadhi:Takeda: Consultancy; Janssen: Consultancy, Research Funding; Cellectar: Research Funding; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy. Bergsagel:Janssen Pharmaceuticals: Consultancy; Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy. Fonseca:AbbVie, Amgen, Bayer, Celgene, Kite, Janssen, Juno, Merck, Pharmacylics, Sanofi, Takeda: Other: Consultant/Advisor; Prognosticatin of MM based on Genetic Categorization by FISH: Patents & Royalties; Adaptive Biotechnologies: Other: Scientific Advisory Board. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kapoor:Amgen: Research Funding; Takeda: Honoraria, Research Funding; Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Janssen: Research Funding. Chanan-Khan:AbbVie: Research Funding; Pharmacyclics: Research Funding; Xencor: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding. Larsen:Janssen Oncology: 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. Russell:Imanis: Equity Ownership. Stewart:Roche: Consultancy; Seattle Genetics: Consultancy; Takeda: Consultancy; Ionis: Consultancy; Janssen: Consultancy, Research Funding; Oncopeptides: Consultancy; Ono: Consultancy; Amgen: Consultancy, Research Funding; Bristol Myers-Squibb: Consultancy; Celgene: Consultancy, Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.