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Introduction Following the launch of the TKI's (tyrosine kinase inhibitors) for the treatment of CML (Chronic myeloid leukemia), establishing its significant control over the disease as evident by multiple studies such as the population based Swedish CML registry reporting that Patients reaching 70 years of age had a relative survival close to 1.0 compared to the normal population with the same age. Consequently, other dimensions have emerged regarding the safety of treatment, particularly the effect on Male fatherhood. This study was conducted to review the real-life data on the effect of TKI on the fatherhood of male patients in the National Center of cancer care and research (NCCCR) in Qatar in the period of 1st of January 2005 - 1st of January 2020. Up to our knowledge, this is the first study addressing the effect of TKI on fatherhood in patients with CML. Methods A single-center study, conducted a mixed-design (retrospective+ phone interviews) with CML male patients in the Chronic or accelerated phase, being followed up in NCCCR, evaluating the effect of Imatinib, Dasatinib, nilotinib, on their fatherhood whether they are taking it as first, a second, or third line of treatment. Inclusion Criteria: -Male patient diagnosed with CML, in Chronic or accelerated phase; 18 years of age or older and actively receiving tyrosine kinase inhibitors including (Imatinib, dasatinib, nilotinib) with the following: -Patients with no known issues with regards to fertility, (fertility is intact) will be included in the study. -Patients who developed fertility issues after the diagnosis of CML and starting TKI's. He has been evaluated by an andrologist and his evaluation concluded its TKI related. Exclusion criteria: -Patients with other MPNS. -Patients not fulfilling inclusion criteria as follow: -Patient known to have infertility before the diagnosis of CML -Patient with infertility after Diagnosis of CML: If a clear underlying cause, not TKI related, will be excluded from the studyif no evaluation was done for infertility and it is not clear whether the infertility is related to an underlying cause or TKI and no proper evaluation by andrologist done excluded from this study The mother has documentation by gynecologist for infertility, or after examining the abortion, still-birth, or IUFD and checking the chromosomal analysis (any mother related cause whether endogenous or exogenous has been excluded) Results: 150 patients were interviewed to be included in the study, 22 (14%) patients had concerns related to medications safety and possible transmission of the disease, 33 (22%) patients had their families completed by the time of diagnosis. 26 patients have met the inclusion criteria, median age around 44 years, median age at diagnosis was 33.5. 100% were in chronic phase, 42.3% were on imatinib, 34.6% on Nilotinib, and 23.1% on Dasatinib. The median TKI exposure period before pregnancy was 3 years. Median age at first conception post TKI treatment is 36, with a median duration of TKI treatment around 7 years. offspring's total number was 43, 97.6% were full-term, had a normal delivery, and normal average weight at delivery. No stillbirths, fetal demise, or congenital anomaly were reported. All offspring had normal development and growth. Median age of children after CML diagnosis around 7 years. No reports of any CML-related cancer in all the offspring Conclusion: Around 98% of male CML patients taking imatinib, Dasatinib, Nilotinib had their offspring born normally with no delivery complications noted, all had no congenital anomaly, had normal growth and development, and no CML-related cancers were diagnosed. Further studies with a larger sample size are required to shed light on the TKI outcome on fatherhood in CML patients. Nonetheless, a call for attention for better education to patients starting on TKI's addressing the possible psychological fear or concerns of having an unsatisfactory effect on their fertility/offspring, targeting better acceptance and adherence to treatment. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. This study evaluates the utilization and cost-effectiveness of (90)Y-IT in the first line treatment for patients with previously untreated low-grade FL (UFL) and marginal zone lymphoma (UMZL) treated at our institution with (90)Y-IT. Methods We utilized the Advanced Text Explorer (ATE) and the Lymphoma SPORE databases to identify two groups of patients with UFL, WHO grade 1-2, and UMZL who received treatment with either (90)Y-IT or bendamustine plus rituximab (BR) at Mayo Clinic Cancer Center between January 2003 and December 2019. We excluded all patients who had >25% bone marrow involvement with lymphoma for the BR group as this was a requirement for (90)Y-IT treatment. Inverse propensity weighting was utilized to balance the groups for baseline patients and disease characteristics. We use progression-free survival (PFS) as a denominator for the cost effectiveness/utilization evaluation. We identified meaningful and retrospectively measurable outcomes to compare between the groups. we extracted the following data; number of clinic visits in the first year after therapy, emergency room visits, number of hospital admissions, number of hospitalization days, numbers of days on the floor and ICU, number of infections, number of neutropenic fever hospitalizations, number of C-difficile events, number of blood products transfusions, overall use of growth factors due to therapy induced neutropenia, average number of times a growth factor was used, and the number of therapeutic use days. We defined days of therapeutic use as the number of days a treatment was administered on. We also calculated the average cost of the induction treatment when utilizing either (90)Y-IT or BR. The therapeutic cost included only the cost of the medications/therapies and their administration. Results Our cohort consists of a total of 143 patients - 64% (92/143) received BR and 36% (51/143) received (90)Y-IT (see Table-1 for clinical characteristics).The median follow-up from the time of therapeutic administration for the (90)Y-IT group was 5.3 years (95% CI; 4.2, 6.2) with one death and 4.7 years (95% CI; 3.9, 4.9) for the BR group with 6 deaths. The ORR was 100% in (90)Y-IT group with 94% achieving complete response (CR) while ORR in the BR group was 98% with 95% achieving CR. Rituximab maintenance was utilized in 33% of BR patients compared to only 6% in patients who received (90)Y-IT, p=0.002. After utilizing inverse propensity weighting (Figure-1), 5 years PFS was 76% for the (90)Y-IT group and 75% for the BR group, p=0.63 (Figure-2). We evaluated the average treatment effect of (90)Y-IT compared to BR on utilization outcomes, Table-2. (90)Y-IT required an average of 4.5 clinic visits less within the first year after treatment compared to BR group, p Transformation to a high grade of lymphoma was seen in 4 patients in the BR group and 2 patients in the (90)Y-IT group. There was only one case of myelodysplastic syndrome in the BR group and none in the (90)Y-IT group. Conclusion Radio-immunoconjugate therapy with (90)Y-IT is a very convenient and cost-effective treatment for low-grade UFL and UMZL. This is especially important amidst the COVID-19 pandemic as it requires less contact with the health system with decreased number of therapeutic days, clinic visits, use of growth factors and number of hospitalization days. The cost of the therapeutic agents and their administration was also significantly lower for the (90)Y-IT which could help reducing the burden on the health system. Figure 1 Figure 1. Disclosures Cerhan: Regeneron Genetics Center: Other: Research Collaboration; Genentech: Research Funding; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; NanoString: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy. OffLabel Disclosure: We are describing the use of Yttrium-90 ibritumomab tiuxetan in the first line setting in comparison to the bendamustine plus rituximab which is the standard of care

Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL. Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method. Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse. Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (>30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29]. Conclusion: 1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected. 2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations. 3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions. 4.Overall prognosis in the literature was poor with most patients surviving 5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size. 6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL. 7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. Figure 1 Figure 1. Disclosures Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

Background: PCL is a rare and aggressive form of multiple myeloma (MM). It is associated with high risk cytogenetics, aggressive disease biology and a dismal prognosis. Dara has revolutionized the treatment of MM leading to deep and durable responses as a single agent and in combination with other agents. We evaluated the efficacy of Dara-based regimens in the treatment of PCL. Methods: Clinical charts of primary and secondary PCL patients treated at the Mayo Clinic Cancer Center between 2012-2019 were reviewed. Survival was analyzed with the Kaplan-Meier method. Plasma cell leukemia was defined by ≥5% peripheral blood plasma cells and/or absolute plasma cell count ≥0.5 x109/L (based on IMWG consensus statement).1 Results: Thirty-one patients were identified (55% female) with a median age at PCL diagnosis of 66 y (range 38-83). Fifteen (48%) had primary (p) PCL, while 14 (52%) had secondary (s) PCL. Nineteen (61%) had high risk cytogenetics with 11 (45%) del 17p, 4 (13%) t(14;16), 14 (45%) 1q amplification/duplication and 3(10%) t(4;14). Twelve (39%) had t(11;14). Eighteen (58%) patients had undergone autologous hematopoietic cell transplant (AHCT) with 12 (39%) having undergone AHCT following their diagnosis of PCL. Patients received a median of 2 prior lines of therapy (range 1-9) prior to receiving Dara-based regimens; 15 (42%) were refractory to an immunomodulatory agent (IMiD), 18 (58%) were refractory to a proteasome inhibitor (PI) and 10 (32%) were refractory to both. Twenty-eight (90%) were IMiD exposed, 31 (100%) were PI exposed. Eighteen (58%) were lenalidomide (R) refractory, 5(16%) were pomalidomide (P) refractory, 8 (26%) were carfilzomib (K) refractory and 13(42%) were bortezomib (V) refractory prior to receiving Dara. Four (13%) received Dara + chemotherapy, 8 (26%) received Dara + PI, 11 (35%) received Dara + IMiD, 5 (16%) received Dara + PI + IMiD and 4 (13%) received single agent Dara. Median follow up time was 26 months (m) (95% CI; 13-61) from diagnosis of PCL and 17m (95% CI; 10-23) from initiation of Dara. Overall response rate (ORR) to Dara-based regimens was 65% (20/31 ≥partial response). The median duration of response was 5.5m (95% CI; 5.6-12.7). The median time to first response was 1m (95% CI; 0.57-1.72) and the median time to best response was 1m (95% CI; 0.7-2.5). Since the start of Dara-based treatment, median progression free survival (PFS) was 4m (95% CI; 2-11, Figure 1A) and median overall survival (OS) was 9 m (95% CI; 5-21, Figure 1B). Patients with pPCL had superior PFS (19 m vs. 3m, p=0.0096) and OS (21 vs. 5m, p=0.0068, Figure 1C) following Dara-based treatment compared to those with sPCL, respectively. Being refractory to an IMiD, PI or both when receiving Dara did not affect PFS or OS. Patients with high risk cytogenetics had similar OS as compared to those with standard risk cytogenetics (8m vs.13m, p=0.89) following Dara-based treatment. After performing a landmark survival analysis at 3m, achieving ≥PR to a Dara-based regimen resulted in a trend towards superior OS (13m vs. 9 m, p=0.07, Figure 1D). Patients who underwent AHCT following the diagnosis of PCL had a superior OS (41m vs. 6m, p=0.020) however there were no PFS or OS differences whether Dara-based regimens were given before or after AHCT. Conclusions: Dara-based regimens induce a high ORR in patients with PCL with a rapid time to first response. However, the OS of patients with PCL, particularly sPCL remains dismal. Prospective trials for PCL patients using novel therapeutic strategies are warranted. 1Fernandez de Larrea, et al. Plasma Cell Leukemia: consensus statement on diagnostic requirements, response criteria, and treatment recommendations by the International Myeloma Working Group (IMWG). Leukemia. 2013; 27(4): 780-791. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Kapoor:Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Dingli:Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Phosplatin: Research Funding; Medimmune: Research Funding; BMS: Research Funding; Cellectar: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Takeda: Honoraria; Amgen: Research Funding; Celgene: Honoraria.

Background: The tumor microenvironment (TME) of MM is characterized by an immunosuppressive milieu fostering MM growth. The impact of tumor associated macrophages (TAM) has not been well-studied in the MM TME. We evaluated the bone marrow biopsies (BMBx) obtained at the initial diagnosis of MM and evaluated the correlation between the number of CD68+ macrophages and clinical parameters and outcomes. Methods: We evaluated the BMBx at initial diagnosis of 34 consecutive MM patients (pts) diagnosed between 2007-2016 at Mayo Clinic Florida. Immunohistochemistry (IHC) was performed with an anti-CD68 (KP1) antibody to identify and count CD68+ TAMs. Survival was analyzed with the Kaplan-Meier method. Chi-square tests were performed to study the correlation between the number of CD68+ TAMs and various clinical parameters. Results: Nineteen (56%) pts were male, 29 (85%) were caucasian. Median age at MM diagnosis was 58.5 years (95% CI 57-63), 18 (53%) pts has ISS I/II disease, 13 (38%) pts had ISS III disease, 3 (9%) has unknown ISS. Eight (24%) had high risk cytogenetics; 4(12%) had del17p, 2 (6%) had t(14;16), 1(3%) had 1q amplification, 3 (9%) had t(4;14). Eight (24%) had t(11;14). Twenty nine (85%) pts underwent autologous transplantation, 11(32%) received maintenance therapy. Overall response rate (≥partial response) to induction therapy was 100%. The ≥ very good partial response (VGPR) rate was 73.5%. Median number of induction cycles was 4.5 (95% CI 4.8-8.3). Twelve (35%) pts received lenalidomide (R)-dexamethasone (D) induction (RD), 9 (26%) received bortezomib (V)-cyclophosphamide(C)-D (VCD) induction, 7 (21%) received VRD induction, 5(15%) received VD induction and 1(3%) received CRD induction. The median follow-up was 92 months (m) (95% CI 85-99) The median progression free survival (mPFS) of the pt population was 40m (95% CI 27-68) and the median overall survival (mOS) was 96m (95% CI 81-126). Mean CD68+ TAM count was 12.5% (95% CI 8.1-16). There was a trend towards improved PFS for patients with ≥5% vs. Conclusion: Pts with ≥5% CD68+ TAM in their initial diagnostic BMBx are more likely to have deeper responses to induction therapy as well as superior OS. In pts induced with an R-based regimen, increased CD68+ TAM was associated with significantly better OS raising the possibility of a therapeutic and mechanistic role of TAM in R-related therapeutic effect. ≥5% CD68+ TAM were noted in patients with lower risk disease as defined by ISS stage but not by cytogenetics. Further exploration of the role of TAM in the biology of MM and its impact on clinical and therapeutic outcomes is warranted. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Tun:DTRM Biopharma: Research Funding; Acrotech: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Mundipharma: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding.

Introduction: Daratumumab (D) is an anti-CD38 monoclonal antibody, used frequently in combination with immunomodulatory drugs (IMiDs), lenalidomide (Len) and pomalidomide (Pom). There are no studies comparing DRd to DPd in Len-exposed or refractory multiple myeloma (MM). We present the Mayo Clinic experience of DPd and DRd utilization and outcomes. Methods: We identified consecutive MM pts who received D, between 1/2015 and 4/2019 at Mayo Clinic. We included pts who were exposed (at least one full cycle, 21/28 days) or refractory (progression on full dose or maintenance Len during treatment or within 60 days of stopping Len) to Len prior to D and received 1 to 4 prior lines of therapy. Only Pts who received DRd and DPd were included. Results: Out of 411 evaluable pts 162 met the inclusion criteria; 67 were Len exposed, but not refractory and 95 were Len refractory. Pts' characteristics are shown in Table 1. DRd was used in 76 (47%) and DPd in 86 (53%) pts. Majority of pts (105; 65%) received DPd or DRd in the 2nd or 3rd line and 104 pts (64%) are still alive. In Len refractory pts, the median time from last dose of Len to D initiation was 1 mths (interquartile range 0-6.5). Seventy pts (43%) had high-risk cytogenetics (HR). Only 11 pts (7%) underwent autologous hematopoietic cell transplant after DPd or DRd regimen. There was no significant difference between pts who received DRd and DPd in terms of age (>65 years), gender, race, proportion exposed or refractory to Bortezomib, number of prior lines of treatment (>2), or HR status (p>0.05 for all). Pts who received DPd were 4 times more likely to be Len refractory compared to pts who received DRd, p=0.0008. Median follow up time for the whole cohort from initial diagnosis was 92 mths (CI 95%; 79.5-107), while from D start date was 30 mths (CI 95%; 27-34). Median PFS for the whole cohort was 21 mths (CI 95%; 15-25) and median OS was 138 mths (CI 95%; 111-193). In Len exposed but not refractory pts, n=67, the overall response rate (ORR) was 82% in the DRd group compared to 68% in the DPd group, p=0.2. There was no difference in median PFS; 25.5 mths (CI 95%; 23-NR) for DRd compared to 25 mths (CI 95%; 5-NR) for DPd, p=0.37. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 138-NR) and 145.5 mths (CI 95%; 70-NR), respectively, p=0.06. In the 48 Len exposed but refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 39 mths (CI 95%; 23-NR) for DRd compared to 21 mths (CI 95%; 3-NR) for DPd, p=0.11. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; NR-NR) and 145.5 mths (CI 95%; 36-NR), respectively, p=0.13. In Len refractory pts only, n=95, the ORR was 84% in the DRd group compared to 58% in the DPd group, p=0.009. There was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 9 mths (CI 95%; 5-15) for DPd, p=0.18. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 78-NR) and 106 mths (CI 95%; 66-183), respectively, p=0.5. In the 57 Len refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 13 mths (CI 95%; 5-NR) for DPd, p=08. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 69-NR) and 105 mths (CI 95%; 47-NR), respectively, p=0.35. In the 16 Len exposed but not refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, the median PFS was better in the DRd group; 24.4 mths (CI 95%; 12-NR) compared to 3.3 mths (CI 95%; 1.9-27.5) for DPd, p=0.0093. However, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 51-NR) and NR mths (CI 95%; 18-NR), respectively, p=0.13. In the 29 Len refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, there was no statistically significant difference in median PFS; 18 mths (CI 95%; 6-43) for DRd compared to 6 mths (CI 95%; 4-13) for DPd, p=0.22.Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 47-NR) and 53 mths (CI 95%; 26-105), respectively, p=0.2. Conclusions: D+IMiD regimens after prior Len exposure/refractoriness are commonly used in real-world, despite the lack of data from prospective clinical trials. Combining D with IMiDs in Len exposed or refractory pts is efficacious, whether the IMiD is Len or Pom. Our study shows that regardless of prior Len use, DRd is at least equivalent to DPd. Prospective studies should be done to confirm these observations. Disclosures Alhaj Moustafa: Acrotech: Consultancy. 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. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding. Fonseca:Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Dingli:Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding.

Background Follicular lymphoma (FL) is the second most common lymphoma accounting for approximately 15% of all non-Hodgkin's lymphoma (NHL). Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. It is approved in relapsed/refractory low-grade NHL and as consolidation after upfront induction chemoimmunotherapy for FL. This study analyzed patients with previously untreated (UFL) or relapsed/refractory low-grade FL (RFL) treated at our institution with (90)Y-IT. It represents the largest reported cohort for therapeutic use of (90)Y-IT in low-grade FL. Methods Medical records of patients with low-grade FL (WHO grade 1-2) who received treatment with (90)Y-IT at Mayo Clinic Cancer Center between January 2003 and December 2018 were analyzed. Overall response rate (ORR) and complete response rate (CR) were calculated. Progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS) were analyzed using the Kaplan-Meier method. Results Our cohort consists of 137 patients - 29% (40/137) with UFL and 71% (97/137) with RFL. The median age at diagnosis was 60 years (range, 18-86) with 54% (74/137) males. The median number of previous treatments in RFL patients was 1 (range, 1-5). ECOG performance status at the time of treatment was 0 in 90% and 1 in 10% of patients. 87% (119/137) had stage III/IV disease at the time of (90)Y-IT therapy. The median follow up from the time of (90)Y-IT therapy was 10.2 years (95% CI; 8.8, 11.6); 69% (95/137) of patients are alive. The ORR was 100% in UFL with 93% (37/40) CR while ORR in UFL was 93% (90/97) with 73% (71/97) CR. 45% (48/108) of the CR patients remain in continuous CR (CCR) with a median follow-up of 7 years (95% CI; 5.2, 9.9). CCR was observed in 55% (22/40) of UFL patients compared to 27% (26/97) of RFL patients. 63% (86/137) of patients had relapsed. More relapses occurred in the RFL group (69/97; 71%) compared to the UFL group (17/40; 43%), (p=0.002). In the entire cohort, the median PFS was 2.5 years (95% CI; 2.1, 3.5) and TTNT was 3.6 years (95% CI; 2.5, 4.7). Median PFS was significantly higher in UFL group compared to RFL group- 4.1 years (95% CI; 2.3, NR) vs 2.2 years (95% CI; 1.6, 3.1), respectively (Figure 1-A). Median TTNT was higher in UFL group compared to RFL group- NR (95% CI; 4.1 years, NR) vs 2.4 years (95% CI; 2, 3.6), respectively (Figure 1-B). Median OS (entire cohort) was 18 years (95% CI; 15.8, NR) with no statistically significant difference between UFL group and RFL group; NR (95% CI; NR, NR) vs 18 years (95% CI; 12.3, 20.5), respectively (Figure 1-C). Transformation to high grade lymphoma was seen in 19% (18/97) in RFL group compared to 2.5% (1/40) in UFL group, (p=0.005). Median time to transformation was 4.3 years (range, 1-11). More patients developed therapy-related myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) in the RFL group 14% (14/97) compared to 2.5% (1/40) in the UFL group (p= 0.02). Median time to develop MDS/AML was 3.3 years (range, 0-9.7). Grade ³3 neutropenia was observed in 46% of patients with median time to recovery of 21 days (range, 2-706). Grade ³3 thrombocytopenia was observed in 47% of patients with median time to recovery of 23 days (range, 7-548). Eighteen patients required growth factors support and 14 required transfusions. Non-hematologic AEs included mild to severe fatigue in 35 patients. Conclusion Radio-immunoconjugate therapy with (90)Y-IT is an effective single-agent regimen for low-grade FL. The response and survival data in this large real-world cohort is superior to the pivotal trials of this agent conducted nearly 20 years ago. The data in untreated FL is also of interest and provides the rationale for our current randomized phase 2 trial in untreated FL (https://clinicaltrials.gov/show/NCT02320292). Long-term complete remission (>7 years) was seen in 35% of the study population. Based on these promising results, clinical trials combining RIC with novel agents that could potentiate its effects are warranted. Figure 1 (A) Progression-free survival; comparing time to progression or death after (90)Y-IT treatment between previously untreated patients (UFL) and patients with relapsed/refractory FL (RFL), (B) Time to next therapy; comparing time to starting next line of treatment after (90)Y-IT treatment between UFL and RFL, (C) Overall survival; comparing time to death from all causes after (90)Y-IT treatment between UFL and RFL. Figure 1 Disclosures Tun: DTRM Biopharma: Research Funding; TG Therapeutics: Research Funding; BMS: Research Funding; Curis: Research Funding; Celgene: Research Funding; Mundi-pharma: Research Funding. OffLabel Disclosure: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. It is approved in relapsed/refractory low-grade NHL and as consolidation after upfront induction chemoimmunotherapy for FL. We are discussing its use as a frontline therapy in low grade FL.

Background: Ibrutinib (ibr) is a small-molecular inhibitor of Bruton's Tyrosine Kinase (BTK), active in the treatment of various B-cell malignancies. B-cell receptor signaling blockade by BTK inhibition using ibr down regulates IRF4 (survival transcription factor) which is down regulated by lenalidomide (R) as well, suggesting possible synergistic effect on cell death. Higher doses of ibr (560-840 mg daily) have been used in combination regimens for MM with no significant dose-limiting toxicities (DLTs) but the combination of ibr and len has not been previously tested. We present safety and preliminary efficacy of the combination ibr, R, and dexamethasone (d) in RRMM patients. Methods: This is a phase I dose escalation study (NCT03015792) of 28-day cycles of ibr (420 mg daily, 560 mg daily, 700 mg daily or 840 mg daily) days 1-28 in combination with R 25 mg PO days 1-21, and d 40 mg PO weekly utilizing a 3+3 dose-escalation design. Eligible RRMM patients had progression after ≥2 prior lines of treatment, measurable disease as per International Myeloma Working Group criteria, ECOG performance status ≤2, adequate bone marrow (BM) (absolute neutrophil count ≥1.0 x 109, platelets ≥50,000 cells/mm3 for patients with BM plasmacytosis Results: As of July 26 2019, 18 patients had been enrolled in the trial. Three patients had to be replaced (2 at 700 mg cohort, 1 each due to withdrawal and ineligibility, and 1 at 840 mg due to withdrawal). Median age of all patients was 67 years (range 49-79) with 9 of the 15 evaluable patients being females. Evaluable patients as per ibr dose level included 3 at 420 mg, 3 at 560 mg, 3 at 700 mg, and 6 at 840 mg. Four out of 15 patients had high-risk cytogenetics. Median prior lines of treatment were 4 (range 2-13) and prior treatments included bortezomib in 87% (n=13), carfilzomib in 47% (n=7), ixazomib in 47% (n=7), lenalidomide in 87% (n=13), pomalidomide in 40% (n=6), thalidomide in 40% (n=6), daratumumab in 60% (n=9), and stem cell transplant in 53% (n=8). High risk cytogenetics [del 17p, t(4;14), t(14;16), t(14;20)] were noted in 4 of the 15 evaluable patients (27%). Median follow up for alive patients was 8.6 months (range 1.1-25.1 months) and the median number of treatment cycles was 2 (range 1-5). Most common reason for treatment discontinuation was PD (40%) followed by adverse events (AEs) (26.7%). Only 1 DLT possibly related to ibr was a grade 3 rash at the 840 mg dose. Grade 3/4 AEs at least possibly related to study treatment included anemia (n=3), thrombocytopenia (n=3), neutropenia (n=3), leucopenia (n=3), lymphopenia (n=2), febrile neutropenia (n=1), and rash (n=2). Overall, the most common all grade AEs included anemia (n=12), thrombocytopenia (n=10), fatigue (n=10), neutropenia (n=8), leucopenia (n=5), and diarrhea (n=5). (Figure 1) No treatment-related deaths were noted. Overall response rate (ORR) was 7% with partial response (PR) noted in 1 patient. Additionally, 1 patient achieved a minor response (MR) and 10 patients had stable disease (SD) for a clinical benefit rate (CBR) of 80%. (Figure 2) PD was noted in 1 patient and 2 patients did not get response assessment. Ibr 840 mg (daily) with R 25 mg (days 1-21) and d 40 mg weekly was considered the MTD of this regimen. The median progression-free survival (PFS) for the 15 evaluable patients was 4.5 months (95% CI: 1.8-not reached). Conclusions: We report the first phase 1 trial of combining a BTK inhibitor with Rd in RRMM patients. MTD of ibr was determined as 840 mg (daily) in combination with R 25 mg (days 1-21) and d 40 mg weekly. This dose of ibr is consistent with some other trials showing the benefit of a higher dose of ibr in various regimens for treatment of B-cell malignancies. We noted this regimen to be well-tolerated without much high-grade AEs. Disease stabilization was noted in majority of patients. These data lay the basis for a larger trial in a more uniform cohort of patients to better define the efficacy of this regimen. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy. Chanan-Khan:AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding. OffLabel Disclosure: Ibrutinib is not FDA-approved for the treatment of multiple myeloma. The regimen of ibrutinib with lenalidomide and dexamethasone is not FDA-approved for the treatment of multiple myeloma.

Targeted agents have greatly improved outcomes for patients (pts) with chronic lymphocytic leukemia (CLL) and other B cell lymphomas; however, single agents have been limited by intolerance, resistance and depth/durability of responses. Current novel targeted agent combinations may improve depth of response, but such "full dose" strategies have been associated with significant AEs, dose reductions/interruptions and discontinuations. Our in vitro & in vivo screening/optimization studies identified that concurrent inhibition of BTK & mTOR targets plus IMiD at low doses of each inhibitor can synergistically kill B-cell malignancies and may address drug-resistance. DTRM-555 is an optimized oral triplet combination of a novel BTK inhibitor DTRMWXHS-12 (DTRM-12) with everolimus (EV) & pomalidomide (POM). This once daily therapy was tested in a stepwise, phase I, US multicenter study in patients with highest unmet medical needs including r/r CLL, Richter's transformation (RT) of CLL, DLBCL, transformed B-cell lymphomas. We conducted a 3+3 design phase I, first human trial exploring DTRM-555 in pts ≥18 years, ECOG PS ≤1 with CLL, B-cell NHL, or Hodgkin lymphoma (HL) with no available standard therapy (NCT02900716). Our goal was to determine optimal doses for triplet combination therapy through 3 escalating phases of study: DTRM-12 in escalating doses (50, 100, 200, & 300 mg/day) in Part Ia, DTRM-12 at 200 mg or 300 mg & EV at 5 mg (doublet or DTRM-505) in Part Ib Arm A while DTRM-12 at 200 mg or 300 mg, EV at 5 mg & POM at 2 mg in Part Ib Arm B. For all arms, treatment was administered for 21 consecutive days of a 28-day cycle, until disease progression or unacceptable toxicity. Safety was the primary endpoint, and the dose-limiting toxicity (DLT) period was cycle 1. Secondary endpoints included response (iwCLL 2018 or Cheson 2014), progression free survival, duration of response and pharmacokinetics. Intra-patient migration between arms (Mono to doublet to triplet) was permitted if subsequent doses were tolerated. The trial commenced 9/27/2016 and completed enrollment 7/25/2019. Thirty-three pts were enrolled, including 2 screen failures and 4 intra-cohort migrations, with r/r DLBCL (n=8), CLL/SLL (n=5), RT (n=6), FL (n=5), MCL (n=4), MZL/LPL (n=3), HL (n=2). 30 of 31 treated pts were evaluated: 8 pts participated in phase Ia (DTRM-12) while 23 pts were treated on phase Ib combinations (DTRM-505 & DTRM-555). Baseline characteristics: 70% male (n=23), median age 70 years (range 46-94) and 94% white. Median prior therapies were 3 (range 1-10), 53% had been treated with ≥1 prior targeted agent (i.e., CD19/CD3 bispecific antibody, obtinutuzumab, pembrolizumab, nivolumab, ibrutinib, venetoclax, PI3k-i), CAR-T or HSCT. 35% pts were previously treated with ibrutinib. Table 1 describes Grade (Gr) 3 and 4 AEs (all causality, stratified by treatment arm). Regarding safety, AEs were manageable, with a total of 5 DLTs were observed: 2 (Gr 3 febrile neutropenia, URI) in part Ib arm A, 3 (Gr 4 thrombocytopenia, Gr 3 diarrhea, G3 febrile neutropenia) in Part Ib arm B. No MTD was reached for the mono & doublet arms, with the MTD of the triplet determined to be DTRM-12 200 mg, EV 5 mg, & POM 2 mg. Spider plot (Figure 1a) shows the clinical response for individual CLL and lymphoma pts treated with mono, doublet and triplet therapies. Depth and durability of response improved with combination therapies (vs. mono). Of note, 48% of all patients had a ≥50% reduction in sum of the products of lymph node diameters. Representative PET-CT scans are in Figure 1b-c. Responses in multi-refractory pts are ongoing (including 15+ mos in a pt with r/r DLBCL and 5+ mos PR in a pt aged > 90 yrs with r/r DLBCL; 4+ & 13+ mos PRs in two pts with RT). DTRM-12 plasma concentrations were unaffected by EV & POM (Once Daily Oral Therapies) in Figure 1d. The clinical trial met its primary endpoint as the triple combination DTRM-555 had an acceptable safety profile. Dose dependent drug levels with minimal inter-pt variations were observed in all arms, supporting once daily oral administration of this low-dose combination therapy. Encouraging clinical activity was observed in several high-risk, multi-refractory CLL and lymphoma pts, including those previously treated with ibrutinib. Thus synthetic lethality is a viable treatment approach. A phase II US expansion study is underway targeting pts with transformed lymphomas (follicular or prior CLL) and r/r DLBCL cohorts. Table 1. Disclosures Mato: AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding; Celgene: Consultancy; AstraZeneca: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Janssen: Consultancy; TG Therapeutics: Consultancy, Other: DSMB member , Research Funding; LOXO: Consultancy, Research Funding; DTRM Biopharma: Research Funding. Schuster:DTRM Biopharma: Research Funding. Foss:Mallinckrodt: Consultancy; Acrotech: Consultancy; miRagen: Consultancy; Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; Eisai: Consultancy; Spectrum: Other: fees for non-CME/CE services . Isufi:Novartis: Consultancy; Astra Zeneca: Consultancy; Celgene: Consultancy. Ding:Merck: Research Funding; DTRM Biopharma: Research Funding. Brander:Novartis: Consultancy; MEI: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; BeiGene: Research Funding; AstraZeneca: Consultancy, Research Funding; Acerta: Research Funding; Tolero: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Teva: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; DTRM Biopharma: Research Funding. Tun:Mundi-pharma: Research Funding; TG Therapeutics: Research Funding; Curis: Research Funding; DTRM Biopharma: Research Funding; Celgene: Research Funding; BMS: Research Funding. He:DTRM Biopharma: Employment, Equity Ownership. Kearney:DTRM Biopharma: Employment, Equity Ownership. Gui:DTRM Biopharma: Employment, Equity Ownership. Anderson:Theradex: Employment. Roeker:AbbVie: Equity Ownership; Abbott Laboratories: Equity Ownership. Huntington:Bayer: Consultancy, Honoraria; AbbVie: Consultancy; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Pharmacyclics: Honoraria; DTRM Biopharm: Research Funding. OffLabel Disclosure: Everolimus in B cell lymphomas and CLL Pomalidomide in B cell lymphomas and CLL

Background MZL is a low-grade non-Hodgkin's lymphoma (NHL) which involves lymph nodes, extranodal sites, or spleen. It is sensitive to radiation therapy, which is used in localized disease with curative intent. Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) that targets CD20. It is approved for relapsed/refractory low grade and follicular NHL. The data on its use in MZL is limited. We present long-term outcome of the largest reported cohort of MZL patients who received (90)Y-IT. Methods Medical records of patients who received treatment with (90)Y-IT at Mayo Clinic Cancer Center between January 2004 and December 2018 were analyzed. We selected patients with MZL and reviewed clinical data including age, gender, MZL type, clinical stage (Ann Arbor Staging System), treatment response, (90)Y-IT related adverse effects (AEs), as well as lymphoma and treatment related events. All patients received (90)Y-IT according to the standard treatment guidelines. Overall response rate (ORR) and complete response rate (CR) were calculated. Progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS) were analyzed using the Kaplan-Meier method. Results Twenty-one patients were identified (Table 1). The median age at diagnosis was 60 years (range, 11-81) and 71% (15/21) were female. 52% (11/21) were previously-untreated (UMZL) while 48% (10/21) were relapsed (RMZL). The median number of pretreatments in RMZL patients was 2 (range, 1-3). ECOG performance status at the time of treatment was 0 in 90% (19/21) and 1 in 10% (2/21). 62% (13/21) were stage III/IV disease at the time of (90)Y-IT therapy. The median follow-up was 8.5 years (95% CI; 4.5, 12.4); 17 (81%) patients remain alive. The ORR was 91% (19/21) with the two non-responders being in the RMZL group. The CR rate was 81% (17/21) and 65% (11/17) remain in CR at a median follow-up of 5.7 years (95% CI; 1.4, 11). Nine (43%) patients had a relapse during the study period. More relapses occurred in the RMZL group (7/10; 70%) compared to (2/11; 18%) in the UMZL group. Median PFS (whole cohort) was 10 years (95% CI; 2.1, NR) and TTNT (whole cohort) was not reached (NR) (95% CI; 2.1 years, NR). Median PFS was significantly higher in UMZL group compared to RMZL group NR (95% CI; 2.5 years, NR) vs 2.1 years (95% CI; 0.17, 9.9), respectively (Figure 1-A).Median OS (whole cohort) was 19.3 years (95% CI; 8.9, 19.3) without statistical difference in between UMZL group and RMZL group NR (95% CI; NR, NR) vs 16.6 years (95% CI; 9, 19.4), respectively (Figure 1-B). None of the 11 UMZL patients died at median follow up of 4.7 years (95% CI; 1.6, 9.2). All 4 deaths were in the RMZL group with 3 dying of transformation to high-grade lymphoma at 8, 22, and 25 months post-(90)Y-IT treatment. One patient died of myelodysplastic syndrome 7.3 years post-(90)Y-IT treatment while in CR. Toxicities were primarily hematologic. Grade ³3 neutropenia was observed in 6/21 (29%) patients with median time to nadir of 48.5 days (range, 19-70) and median time to recovery to normal absolute neutrophil count of 39.5 days (range, 7-476). Grade ³3 thrombocytopenia was observed in 3 (14%) patients with median time to nadir of 35 days (range, 19-357) and median time to recovery of 21 days (range, 2-538). Grade ³3 anemia was observed in only one patient. Only two patients required transfusions and growth factor support. Non-hematologic AEs included mild to severe fatigue in 4 patients. Conclusion RIC with (90)Y-IT is efficacious and well-tolerated in patients with previously untreated as well as relapsed MZL. As expected it appears to be more efficacious in previously untreated patients. Long-term complete remission (>5 years) was observed in 52% of the study population (43% of UMZL and 9% of RMZL). Combination of efficacy, tolerability, and treatment schedule most convenient for patients makes (90)Y-IT a reasonable alternative to systemic therapy with immunotherapy, chemotherapy, or chemo-immunotherapy in management of MZL. Figure 1: (A) Progression-free survival; comparing time to progression or death after (90)Y-IT treatment between previously untreated patients (UMZL) and patients with relapsed MZL (RMZL), (B) Overall survival; comparing time to death from all causes after (90)Y-IT treatment between UMZL patients and RMZL patients. Disclosures Tun: Curis: Research Funding; TG Therapeutics: Research Funding; BMS: Research Funding; DTRM Biopharma: Research Funding; Celgene: Research Funding; Mundi-pharma: Research Funding. OffLabel Disclosure: The use of Yttrium-90 ibritumomab tiuxetan as a first line treatment for marginal zone lymphoma

Introduction: Monoclonal gammopathy (MG) is a spectrum of conditions including monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). MM is the second most common hematologic malignancy. Despite advances in the treatment of MM it remains an incurable disease that accounts for > 80 000 deaths annually worldwide. Many etiologies for myelomagenesis have been postulated. One theory suggests that chronic antigen stimulation from rheumatologic conditions can increase the risk of MG. Numerous studies have reported an increased risk of MG and other lymphoproliferative disorders in patients with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). However, the association between rheumatoid arthritis (RA) and MG is controversial as conflicting results have been reported. Case control studies have described an increased risk of RA but this finding was not corroborated in a subsequent meta-analysis. We used the national inpatient sample (NIS) database to explore the association of RA with MGUS and MM. Methods: The NIS is a validated database derived from discharge billing information which provides a sample of all non-federal hospital discharges in the Unites States. We identified adult patients with discharge diagnosis codes for MGUS (ICD-9 273.1), MM (ICD-9 203.0), RA (ICD-9 714.0), SLE (ICD-9 710.0) and SS (ICD-9 710.2) from 2014. Demographic data such as age, sex and race were also obtained. Multiple logistic regressions were used to analyze data for association of RA with MGUS and MM after adjusting for age, gender, race and other rheumatic diseases. Statistical analysis was performed with STATA 14. Results: A total of 7,071,762 discharges were analyzed. There were 20,066 hospitalized adults with discharge diagnosis codes for MM and 6,433 patients with a discharge diagnosis of MGUS. The prevalence of RA in patients with MGUS is 5.1% (p Discussion: Our review of the NIS database found a significant association between rheumatologic disorders (RA, SLE and SS) and MGUS. These results are in concordance with previous retrospective studies. However, we did not find a significant relationship between RA and MM. There is known to be a high prevalence of MGUS in the general population, the clinical significance of which is being debated. The association between RA and MGUS that our study found may be due to a selection bias as patients with rheumatic conditions such as RA are tested more frequently for MGUS than the general population. Disclosures No relevant conflicts of interest to declare.