Diabetes mellitus and risk of plasma cell and lymphoproliferative disorders in 94,579 cases and 368,348 matched controls

this research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 (UAS) and supported by grants from Swedish Cancer Society (MB), Parker Institute of Cancer Immunotherapy Career Development Award (YD, UAS), International Myeloma Society Career Development Award, Paula and Rodger Riney Foundation, American Society of Hematology Clinical Research Training Institute Award and TREC Training Workshop R25CA203650 (PI: Melinda Irwin) (UAS). Copyright & Usage Copyright (c) 2022 Ferrata Storti Foundation Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.Peer reviewe

Design of a multicentre randomized trial to evaluate CT colonography versus colonoscopy or barium enema for diagnosis of colonic cancer in older symptomatic patients: The SIGGAR study

Background and Aims: The standard whole-colon tests used to investigate patients with symptoms of colorectal cancer are barium enema and colonoscopy. Colonoscopy is the reference test but is technically difficult, resource intensive, and associated with adverse events, especially in the elderly. Barium enema is safer but has reduced sensitivity for cancer. CT colonography ("virtual colonoscopy") is a newer alternative that may combine high sensitivity for cancer with safety and patient acceptability. The SIGGAR trial aims to determine the diagnostic efficacy, acceptability, and economic costs associated with this new technology.Methods: The SIGGAR trial is a multi-centre randomised comparison of CT colonography versus standard investigation ( barium enema or colonoscopy), the latter determined by individual clinician preference. Diagnostic efficacy for colorectal cancer and colonic polyps measuring 1 cm or larger will be determined, as will the physical and psychological morbidity associated with each diagnostic test, the latter via questionnaires developed from qualitative interviews. The economic costs of making or excluding a diagnosis will be determined for each diagnostic test and information from the trial and other data from the literature will be used to populate models framed to summarise the health effects and costs of alternative approaches to detection of significant colonic neoplasia in patients of different ages, prior risks and preferences. This analysis will focus particularly on the frequency, clinical relevance, costs, and psychological and physical morbidity associated with detection of extracolonic lesions by CT colonography.Results: Recruitment commenced in March 2004 and at the time of writing ( July 2007) 5025 patients have been randomised. A lower than expected prevalence of end-points in the barium enema sub-trial has caused an increase in sample size. In addition to the study protocol, we describe our approach to recruitment, notably the benefits of extensive piloting, the use of a sham-randomisation procedure, which was employed to determine whether centres interested in participating were likely to be effective in practice, and the provision of funding for dedicated sessions for a research nurse at each centre to devote specifically to this trial

FDA Analysis: Impact of Body Mass Index (BMI) on Outcomes in Relapsed-Refractory Multiple Myeloma

Background: Obesity has been implicated as a risk factor for the development of certain types of cancers, including multiple myeloma (Wallin 2011). In a report published in NEJM in 2016, the relative risk of multiple myeloma for overweight to class 1 obese individuals was 1.2, versus a relative risk of 1.5 for class 2 to 3 obese individuals (Lauby-Secretan 2016). Recent reports indicate that BMI may impact prognosis in patients with newly diagnosed multiple myeloma (Beason 2013). Minimal information is available on impact of BMI and prognosis in patients with relapsed-refractory multiple myeloma. We analyzed the association between BMI and clinical outcomes in patients with relapsed/refractory multiple myeloma to determine if there is a difference in outcomes based on body weight. Methods: We conducted a retrospective analysis of four clinical trials evaluating novel therapeutics. These trials enrolled patients with relapsed/refractory multiple myeloma who had received one or more prior therapies. Patients were categorized into four groups, underweight (BMI 30.0 kg/m2). The Kaplan-Meier method was used to estimate progression free survival and overall survival. Results: A total of 2392 subjects were included in this analysis. The median age was 65 years (range 30-91 years). A total of 28 (1.2%) subjects were underweight, 733 (30.6%) were normal weight, 1032 (43.1%) were overweight, and 599 (25.0%) were obese. More of the underweight subjects were female (82.1%), whereas more of the overweight and obese subjects were male (62.9% and 56.6%, respectively). The median PFS and OS K-M curves are displayed below. In this univariate analysis, there were no differences in PFS (p=0.61) or OS (p=0.7) among the four groups. There were some differences in the underweight population; however, the small sample size of this group precludes any meaningful conclusions. Univariate analyses by gender did not reveal any differences in outcomes based on body weight. Conclusion: In patients with relapsed/refractory multiple myeloma, body weight had no impact on outcomes, as measured by PFS and OS. These results are consistent with previous findings on the effect of BMI on survival in subjects with multiple myeloma after autologous stem cell transplant (Kocoglu 2018). Limitations of this analysis include the use of a univariate analysis, the small sample size for patients who were underweight, heterogeneity in the treatment regimens, and immaturity of the OS data. Future studies are needed to evaluate other variables such as the relationship between cytogenetics and body weight, as well as analyses of safety based on body weight in this relapsed/refractory patient population. Figure Disclosures Shah: Physicians' Education Resource: Honoraria. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Landgren:Sanofi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Merck: Other: IDMC; Theradex: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding

MALDI-TOF Mass Spectrometry in Serum for the Follow-up of Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab-Based Combination Therapy

Introduction Mass spectrometry-based methods have been shown to be more sensitive for detecting monoclonal proteins (M-protein) in serum compared to current electrophoretic techniques, serum protein electrophoresis (SPEP) and immunofixation (IFE). In particular, MALDI-TOF mass spectrometry (MALDI-TOF MS) may soon replace these techniques for the routine monitoring of multiple myeloma (MM) patients due to its relatively low cost and high throughput. In this study, we evaluate the performance of MALDI-TOF MS in the follow up of newly diagnosed multiple myeloma (NDMM) patients treated with a daratumumab-based combination therapy. We report our findings compared to SPEP and IFE results and discuss the advantages and disadvantages of the technique in the serial analysis of patients. Patients and Methods Twenty-seven NDMM patients treated with daratumumab-based combination therapy were included in this study; median age 57 years (range 33-79 years) and 52% were males. Each patient had 10 time points of follow-up: baseline, day 15 of cycle 1, the first day of each cycle from cycle 2 to cycle 8, and at the end of treatment (EOT). All samples were analyzed in a blinded fashion by MALDI-TOF MS. First, immunoglobulins were purified from serum using magnetic beads specific for IgG and IgA heavy chains or kappa and lambda light chains. Immunoglobulins were eluted from the beads and the light chains and heavy chains were separated by adding a reducing agent. Purified samples were analyzed using a Microflex LT MALDI-TOF mass spectrometer (Bruker). Samples taken at baseline were used to identify the mass to charge ratio (m/z) of the M-protein which served as a surrogate marker in the analysis of subsequent samples. MALDI-TOF MS results were compared to SPEP, IFE and the kappa/lambda free light chain (κ/λ) ratio. Results At baseline, IFE and MALDI-TOF MS were positive for all 27 patients while SPEP was negative for M-protein in 2 patients. Different M-protein isotypes were observed including 3 free kappa, 1 free lambda, 15 IgG kappa, 3 IgG Lambda, 3 IgA kappa and 2 IgA lambda. The κ/λ ratio was abnormal for 26/27 patients. Twenty-three patients completed the 8 cycles of treatment. During the follow-up, 14 of the 23 patients remained positive until the EOT by MALDI-TOF MS. Regarding these patients, 3 were negative by SPEP and IFE at the EOT. Nine of the 23 patients became negative by MALDI-TOF MS in a median time of 5 cycles (range 2- 8). Among these 9 patients, 1 reached a complete response (CR) and 6 reached stringent CR in a median time of 3 cycles (range cycle 2 - EOT). The 2 patients that did not reach CR but were negative by MALDI are suspected to have a false positive IFE result. These patients' IgG kappa M-protein overlaps with daratumumab on IFE and the Hydrashift assay (Sebia) was unavailable at the time of analysis. In these cases, MALDI provided better specificity compared to IFE as the M-protein could be distinguished from daratumumab based on m/z. However, daratumumab could not always be distinguished from the M-protein at some timepoints for some patients. The patient that still had an abnormal κ/λ ratio but was negative by MALDI had κ light chain MM. MALDI-TOF MS may be less sensitive for the detection of free light chains in serum. We observed differences between the M-spike intensity of the heavy- and light-chain specific purifications especially when the M-protein was at low levels. This may be due to differences in the polyclonal background for each purification reaction and will affect the sensitivity of M-protein detection. Conclusions This study is important because it helps to understand the performance of MALDI-TOF MS in the follow-up of MM patients under therapy. The use of serial samples allowed us to characterize patterns of immune markers longitudinally in relation to given therapy. The m/z ratio at baseline is a key for the interpretation during the follow-up and to avoid interference with other monoclonal immunoglobulins, like daratumumab, for example. When more than one monoclonal immunoglobulin is present, their relative concentration, not just their m/z values, is important for distinguishing two different peaks. MALDI-TOF MS is useful for monitoring patients under therapy because it provides higher specificity and sensitivity than electrophoretic methods. This may be especially important in clinical trials and in accurately defining CR and sCR. Disclosures Lesokhin: BMS: Consultancy, Honoraria, Research Funding; GenMab: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Genentech: Research Funding; Janssen: Research Funding; Serametrix Inc.: Patents & Royalties; Takeda: Consultancy, Honoraria. Mailankody:Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria; Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Hassoun:Janssen: Research Funding; Novartis: Consultancy; Celgene: Research Funding. Landgren:Abbvie: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Merck: Other: IDMC; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding

An Observational, Retrospective Analysis of Retreatment with Carfilzomib in the Management of Patients with Multiple Myeloma

Background: Several studies have indicated that the depth and duration of treatment response in multiple myeloma are both reduced in the relapsed setting. With further lines of therapy, responses continue to weaken in depth and shorten in duration. The National Comprehensive Cancer Network (NCCN) Guidelines suggest that regimens may be repeated in the relapsed setting if there has been a duration of at least 6 months since that regimen was given; however, there is limited information regarding treatment response and duration in the setting of re-treating patients with agents previously utilized. Moreover, preliminary data has suggested that carfilzomib-based regimens in the frontline may be able to attain deeper and longer responses than alternative therapies, which has led to carfilzomib being used more frequently in the frontline. This motivated us to investigate the treatment response, depth, and safety of re-challenging patients with carfilzomib in the relapsed setting. Methods: In this retrospective chart review, we identified all patients who were treated with multiple courses of carfilzomib-based regimens at Memorial Sloan Kettering Cancer Center between January 1, 2014 and November 30, 2018. Our primary objectives were to assess the response, duration of response and treatment, and safety of re-exposure to carfilzomib-based regimens. Responses were assessed as per IMWG 2016 consensus criteria (Lancet Oncol 2016). In this review we describe the clinical course, safety, and efficacy of re-challenging patients with carfilzomib in the relapsed and refractory settings. Results: Fifteen patients were identified as having received multiple, independent lines of carfilzomib-based therapy. The median age of the cohort was 58 years (49-76) with 53% male (8); two patients had R-ISS stage 1, eight stage 2, and five stage 3 disease. Five of these patients received their initial carfilzomib in the frontline as part of KRD; four of whom attained a sCR with the fifth attaining a VGPR. The remaining ten patients received their initial carfilzomib in the second-line (4) or 3rd and subsequent lines (6). Upon re-exposure to carfilzomib, patients were heavily treated with a median of four lines of therapy (2-15). All but three patients had at least one adverse cytogenetic abnormality; eight with 17p-, five with 13q-, three with t4;14, and six with 1q+. Regimens utilized in the relapsed setting included KRD (N=4), KPD (N=3), Cyklone (N=2), KD + HDAC inhibitor (N=3), KD (N=1), KCD (N=1), and KRD + daratumumab (N=1). Four patients received carfilzomib at a dose of 27 mg/m2 while the remaining 10 received > 36 mg/m2. Responses were seen in all but four patients (two VGPR, five PR, and four MR), with one patient experiencing progression during carfilzomib with no response; notably, this patient only attained a MR to primary carfilzomib therapy and their second exposure was the 15th line of therapy. The median time to next therapy was 4.8 months (1.9-19.4) with one patient being bridged to autologous hematopoietic cell transplantation (HCT), one to allogeneic HCT, and three are currently receiving ongoing carfilzomib treatment (13.9, 2.8, 2.5 months with VGPR, MR, and PR, respectively). Exacerbation of baseline hypertension was identified in three patients, but these instances were treated successfully with standard medications with no further complications. No additional cardiovascular events were identified in the frontline or re-treatment settings. Conclusions: We report that in a heavily pre-treated, high risk patient cohort, patients previously treated with carfilzomib-based regimens may be safely re-challenged with carfilzomib. Importantly, none of these patients experienced cardiovascular adverse effects other than exacerbation of underlying hypertension, further supporting the ability to safely re-treat a select group of patients with carfilzomib. We conclude that depending on the patient and treatment history, re-challenging with carfilzomib at relapse may be appropriate salvage therapy, particularly as a bridge towards HCT and/or clinical trials. Disclosures Hassoun: Novartis: Consultancy; Janssen: Research Funding; Celgene: Research Funding. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Lesokhin:Genentech: Research Funding; Serametrix Inc.: Patents & Royalties; Janssen: Research Funding; GenMab: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Landau:Prothena: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria. Shah:Janssen Pharmaceutica: Research Funding; Amgen: Research Funding. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Giralt:Amgen: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Miltenyi: Research Funding; Jazz Pharmaceuticals: Consultancy; Actinium: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Johnson & Johnson: Consultancy, Research Funding; Kite: Consultancy. Landgren:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Merck: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding

VRd Versus KRd Safety Profiles in Newly Diagnosed Multiple Myeloma Patients Using Real-World Evidence Data from a Single Institution: VRd Has High Rates of Chronic Neuropathy, and KRd Has Low Rates of Cardiopulmonary or Renal Toxicities When Using Optimized IV Fluid Management Coupled with Baseline Cardiac Workup

Background The use of immunomodulatory agents and proteasome inhibitors in newly diagnosed multiple myeloma (NDMM) patients has improved outcomes and led to their widespread use as induction regimens independent of transplant eligibility. Although the overall toxicity profiles of these regimens are considered favorable, their prolonged use warrants a heightened vigilance for toxicities during therapy, and treating physicians need to carefully balance efficacy and toxicity profiles for each patient. Given that patients enrolled on clinical trials, per eligibility criteria, are less frail and/or have fewer comorbidities than patients in the general population, we were motivated to conduct a large study designed to define the safety profiles of the most commonly used induction regimens in the US, based on real-world evidence data. Methods We identified 185 consecutive NDMM patients treated with bortezomib, lenalidomide, and dexamethasone (VRd) vs. carfilzomib, lenalidomide, and dexamethasone (KRd) at MSKCC between 2015 and 2019. By reviewing all available data for these patients, we defined the incidence of cardiopulmonary toxicities, hypertension, renal complications, and peripheral motor or sensory neuropathy. Results A total of 81 and 104 patients were treated with VRd and KRd induction, respectively (Table 1). The VRd (compared to KRd) group had a smaller proportion of patients with high-risk cytogenetics (36% vs. 55%, P=0.01); yet, the >CR rate was lower in the VRd (compared to KRd) group (28% vs. 45%, P=0.02) (Table 2). Table 3 summarizes select toxicities. The incidence of cardiopulmonary AEs was similar in both groups: 12% (N=9) and 10% (N=11) in the VRd and KRd groups, respectively, with the majority limited to grade 1 and 2 (P=1.00); observed cardiac toxicity was reversible in 8 of 9 (89%) vs. 9 of 11 (82%) patients. Renal toxicity was rare in both groups (2% vs. 4% for VRd vs. KRd, P=0.70). New onset or worsening of pre-existing (at baseline) neuropathy was significantly (P2), and 26/45 (58%) patients developed chronic neuropathy after completion of induction therapy. These patients required various interventions, including opiates (N=7), pregabalin/gabapentin/duloxetine (N=17), rehabilitation/physical therapy (N=2), assistive devices such as canes, walkers, and wheelchairs (N=3). None of the patients treated with KRd had new onset neuropathy requiring pain medication. In the VRd group, neuropathy resulted in treatment discontinuation for 6 (7%) patients. Overall, 9% and 4% of patients treated with VRd and KRd, respectively, had treatment discontinuation due to AEs (P=0.22). There were no deaths in the two groups. Conclusion Using real-world evidence data, we defined the safety profiles of VRd and KRd. In sharp contrast to clinical trials mandating recurrent IV fluids before/after administration of carfilzomib, we use optimized IV fluid management (250 ml saline before dose 1 of cycle 1, thereafter no IV fluids) coupled with baseline work-up, including EKG and echocardiogram, for all patients treated with KRd. Therefore, we did not observe excess rates of cardiopulmonary or renal AEs with KRd, and the majority were reversible. In the VRd group, 45 (56%) patients developed new onset or worsening neuropathy, and a third of these developed sensory alteration or paresthesia interfering with function and/or symptomatic weakness interfering with function, or more severe forms of neuropathy. Overall, about 30% of all VRd treated patients developed chronic neuropathy after induction therapy, including disabling neuropathy in some patients and often with need for continued pain treatment. Neuropathy resulted in treatment discontinuation for 7% of patients treated with VRd. These real-world evidence data demonstrate the general tolerability and efficacy of KRd induction, with less severe neuropathy compared to VRd. Disclosures Hultcrantz: Daiichi Sankyo: Research Funding; Amgen: Research Funding; Intellisphere LLC: Consultancy; GSK: Research Funding. Korde:Amgen: Research Funding; Astra Zeneca: Other: Advisory Board. Lesokhin:GenMab: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Juno: Consultancy, Honoraria; Janssen: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding. Mailankody:Allogene Therapeutics: Research Funding; Physician Education Resource: Honoraria; PleXus Communications: Honoraria; Takeda Oncology: Research Funding; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding; Janssen Oncology: Research Funding. Hassoun:Takeda: Research Funding; Novartis: Consultancy; Celgene: Research Funding. Shah:Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Scordo:Kite - A Gilead Company: Other: Ad-hoc advisory board; Omeros Corporation: Consultancy; Angiocrine Bioscience, Inc.: Consultancy, Research Funding; McKinsey & Company: Consultancy. Chung:Genentech: Research Funding. Shah:Amgen Inc.: Research Funding; Janssen: Research Funding. Lahoud:MorphoSys: Other: Advisory Board. Giralt:Actinuum: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Quintiles: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Jazz: Research Funding; Kite: Research Funding; Sanofi: Research Funding; Adienne: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Seattle Genetics: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Seattle Genetics: Research Funding; Juno: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Celgene: Consultancy, Honoraria, Research Funding

Diabetes Mellitus and Risk of Plasma Cell and Lymphoproliferative Disorders: A Population Based Study Including 94,579 Cases and 368,348 Matched Controls

Introduction The incidence of lymphoproliferative disorders (including plasma cell disorders) (LPD) and diabetes mellitus (DM) increase with age. The metabolic link between DM and multiple myeloma (MM) or LPD has been researched in other epidemiologic studies with a small number of cases suggesting an increased risk (Dankner et al Am J Epi 2016, Castillo et al Blood 2012). However, this link has not yet been studied in patients with related disorders such as monoclonal gammopathy of unknown significance (MGUS), AL amyloidosis (AL), or Waldenstrom macroglobulinemia (WM). This is the first study to evaluate the risk of DM on LPD in a large Swedish population-based case-control study. Methods We conducted a large population-based matched case-control study to evaluate the impact of a preceding diagnosis of DM on the development of a LPD. We included all cases of MM, WM, AL and other LPs (OLP) in the nationwide Swedish Cancer Registry and cases of AL and chronic lymphocytic leukemia (CLL) in the Swedish patient registry from 1987-2013. MGUS was acquired from a network of oncology and hematology clinics in Sweden. OLPs included the diagnoses of Hodgkin lymphoma, non-Hodgkin lymphoma, CLL, T cell lymphoma and other lymphocytic leukemias. For each case, up to four controls matched by age, gender, and county of residence from the general population were included. Cases with no controls were excluded. Diagnoses of DM were acquired from the Swedish patient registry where they were coded using ICD 9 and 10 codes. Conditional logistic regression was then performed controlling for the matching variables estimating the odds ratio (OR) of each LPD for a diagnosis of DM before the diagnosis of the LPD. OR of each LPD for the diagnosis of DM greater than one year and less than one year prior to the diagnosis of LPD was also calculated. For MGUS cases, we also assessed the risk of progression to LPD. To avoid immortal time bias we include DM as a time dependent covariate in a Cox-model adjusting for age, sex, and year of MGUS diagnosis. All analyses were performed in R using the survival, and survminer packages. Results Patients with a diagnosis of MGUS (OR: 1.58; p 1 year prior to the diagnosis were included (Table 1). However, patients with (vs. without) a diagnosis of DM are not more likely to progress from MGUS to MM, WM, AL or OLP (HR 0.89; p=0.11) (Table 2). Discussion The strength of our study lies in its large sample size and the availability of 4 matched controls for each case. The diagnosis of DM is associated with an increased risk of MGUS, MM, AL and OLP. This risk is greatest for DM diagnosis in the year prior to LPD diagnosis. This may be due to DM induced hyperglycemia leading to epigenetic changes that increase the odds of developing/accelerating early stage cancer given that they may have prediabetes/undiagnosed DM for many years prior (Huang et al Diabetologia 2014). It is also plausible that patients with DM for >1 year have been on metformin which has been shown to have a protective effect and are less likely to progress suggesting the role of hyperglycemia in its progression (Chang et al Lancet Haematol 2015). Alternatively, patients are likely to have DM diagnosed in the year prior due to similar symptoms of fatigue or weight loss, or a detection bias due to increased physician visits and laboratory testing. This lack of increased progression from MGUS in DM may be explained by the small numbers of patients that progressed in this dataset or the inability to control for factors such as DM treatment. Some other limitations include the lack of granular information related to DM, body mass index as well as prognostic information for the LPD. Conclusions Although, smaller prior studies have suggested a link between DM and cancer including MM and LPD, this is the largest study in patients with LPD. This is also the first epidemiologic study establishing a link between DM and MGUS as well as AL. Research into further understanding this association would enable us to provide patients with better treatment options in the future. Disclosures Shah: Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Hultcrantz:Intellisphere LLC: Consultancy; Amgen: Research Funding; Daiichi Sankyo: Research Funding; GSK: Research Funding. Hassoun:Takeda: Research Funding; Celgene: Research Funding; Novartis: Consultancy. Korde:Astra Zeneca: Other: Advisory Board; Amgen: Research Funding. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Janssen: Research Funding; Genentech: Research Funding; Juno: Consultancy, Honoraria. Mailankody:Physician Education Resource: Honoraria; PleXus Communications: Honoraria; Takeda Oncology: Research Funding; Janssen Oncology: Research Funding; Allogene Therapeutics: Research Funding; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Seattle Genetics: Research Funding; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding