Citations

Abstract Background:Racial disparities in multiple myeloma (MM) outcomes are well established. Clinical characteristics and cytogenetic abnormalities dictate outcomes in MM but historically they have been mostly defined in White patients with paucity of information regarding racial-ethnic minorities. Hispanics are the fastest growing racial-ethnic subgroup in United States and have the worst overall survival (OS) in MM but differences in disease presentation among Hispanics compared to Whites, the historical control, are undefined. Methods: MM patients seen at Mayo Clinic in Florida (MCF) and Arizona (MCA) between 1/1/2000-06/15/2017 were included. Patient and disease characteristics including gender, age at diagnosis, bone marrow (BM) plasmacytosis, laboratory data [M spike, creatinine (Cr), beta-2-microglobulin (B2M), Hemoglobin (Hb), calcium (Ca)], MM subtype [IgG, IgA, light chain (LC), other], LC subtype (κ, λ, biclonal), presence of lytic bone lesions, disease stage (DS, ISS, R-ISS), mSMRT cytogenetic risk category, presence of individual cytogenetic mutations (deletions, translocations, gains, trisomy/hyperdiploidy) was collected. Comparisons between Hispanic study cohort characteristics and historical control were made by Chi-square, Fischer's exact and Signed rank tests, where applicable, using data from previous publications [Kyle et al, 2003 (n=1027) and Fonseca et al, 2003 (n=351)]. Patients with missing data on a certain clinical or disease feature were not included in the statistical analysis of that specific characteristic. Results: A total of 1705 MM patients were screened and 266 Hispanic patients seen at either site between the specified dates were identified for the analysis. These included equal number of males and females (n=133 each) with a median age of 58 years (range 25-87). IgG disease was seen in 52% with IgA and LC subtypes in 23% each. LC subtype was κ in 67%, λ in 31% and biclonal in 2% cases. Lytic and extramedullary disease were noted in 71% and 44% patients, respectively. DS and R-ISS stage at the time of MM diagnosis was not available in most patients while ISS stage among 150 patients showed stage 1, 2 and 3 in 48%, 28% and 24% patients, respectively. mSMART risk categories were present in 226 patients and included high, intermediate and standard risk in 12%, 11% and 77% patients, respectively. Of these 226 patients, cytogenetic disease prior to starting any MM treatment was available in 153 patients with similar risk category distribution. Median follow up for the whole Hispanic cohort was 38.6 months with a median OS 10.7 years (Figure 1). Comparison with historical control datasets which were 97% or greater comprised of White patients showed some significant differences for the Hispanic cohort including gender distribution, median age, BM plasmacytosis at the time of diagnosis, median Hb, Cr or M spike at presentation, light chain subtype, presence of lytic bone disease and certain cytogenetic alterations including t(4;14) and del13q/monosomy (Table 1). We did not note differences in high-risk cytogenetics between Hispanics and historical White controls. Conclusions: We report the first description of clinical and cytogenetic characteristics of Hispanic MM patients. The current and historical datasets that we have used are all from Mayo Clinic experience, thus making reasonable comparisons possible. We were able to confirm previous reports of demographic differences in Hispanics e.g., younger age at diagnosis. While some characteristics were significantly different, the clinical and cytogenetic differences we note do not clearly explain the inferior OS noted for Hispanics in population-based studies. Significant differences that we report warrant continued exploration in larger institutional and public databases in addition to a continued look into healthcare access and utilization. An ongoing collaborative analysis with data from Mayo Clinic, University of Miami and University of Southern California, Los Angeles is ongoing. Disclosures Fonseca: AMGEN: Consultancy; Jansen: Consultancy; Mayo Clinic & Dr Fonseca: Patents & Royalties: Prognostication of myeloma via FISH, ~$2000/year; Celgene Corporation: Consultancy, Research Funding; Merck: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pharmacyclics: Consultancy; Novartis: Consultancy. Kelly: Pharmacyclics: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Jannsen: Honoraria. Sher: LAM Therapeutics, Inc: Research Funding. Ailawadhi: Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Abstract Background: SCT is a standard therapeutic approach for patients with MM and has contributed to improved outcomes. While SCT utilization in MM has increased for all racial-ethnic subgroups over time, population-based studies have repeatedly shown that racial minorities are less likely to receive it. We explored factors that determine SCT utilization among patients within a given race to understand intra-racial disparities and how to address them in order to maximize the use of this imperative treatment among eligible patients. Methods: The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004-2013 was studied. Cases without information on the selected patient or facility characteristics evaluated in this analysis, including SCT use, race, median income, insurance status or facility type of initial MM diagnosis and/or treatment were excluded. The association between utilization of SCT as part of initial therapy of MM and socio-demographic factors was studied stratifying patients into mutually exclusive racial-ethnic subgroups non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA) and others using multivariate GEE logistic regression analysis (clustered on facility ID). Interactions between race and patient/facility characteristics and SCT utilization were tested using similar methods but including all races. Results: Of the 123480 unique MM patients in NCDB diagnosed between 2004-2013, 111799 met the inclusion criteria. Of these, 15021 patients (13.4%) received SCT as part of initial MM therapy. Of those who received SCT, 77.5% were NHW (14.4% of all NHW), 15.1% NHB (10.3% of all NHB), 5.2% Hispanics (13.2% of all Hispanics), 2% NHA (15.5% of all NHA) and <1% others. There was no difference by gender but significantly reduced odds of receiving SCT were noted for every 10-year increase in age at diagnosis for all racial subgroups. NHA were the only subgroup not to have a significant year-wise increase over time in odds of receiving SCT between 2004-2013. A significant increase in SCT utilization was seen with increasing median income (quartiles; 2008-2012 data), for NHW and Hispanics but not for NHB and NHA, while increased education (% population with high-school degree; 2008-2012 data) was associated with a significant increase in SCT use for NHW and NHB, but not among Hispanics or NHA. An increase in great circle distance (GCD) from the treating facility as well as a lower Charlson-Deyo comorbidity index (CCI) was associated with significantly increased odds of receiving SCT for all racial groups. Insurancepayer status significantly affected odds of receiving SCT among all races with those having private insurance to be most likely to receive SCT among NHW, NHB and Hispanics while those with "other government" insurance payer type being most likely among NHA. Among treating facility characteristics, patients of all races were more likely to receive SCT if treated at an academic/researchfacility (including NCI-designated centers) or centers with highest quartile of patientvolume seen. For analysis by geographicalregion, NHW and NHA had the highest odds of receiving SCT in mountain region but there was no impact of geography on SCT for NHB or Hispanics. Odds ratio (OR) of receiving SCT as part of initial MM therapy by socio-demographic and facility characteristics for patients of individual racial subgroups are shown in Table 1. A significant interaction between odds of receiving SCT and various racial subgroups was noted for patient age at diagnosis (p<.001, decreased odds among NHW and NHA), GCD from treating facility (p=0.013, increased odds among NHB and NHA), CCI (p=0.043, decreased odds among NHA) and treatment facility volumes (p=0.046, increased odds among NHA and Hispanics). Conclusions: In the largest analysis exploring socio-demographic factors affecting SCT utilization in MM we note a significant disparity within races for who gets SCT as a part of initial MM management and who does not. While some of these factors are non-modifiable, others including access to healthcare, income, insurance and literacy levels, proximity to treatment center, treating facility type as well as volumes are modifiable and appear to be barriers to SCT among in some races, while not in others. These must be addressed to minimize disparities within racial subgroups, especially the minorities and realize maximal benefit of SCT for MM. Disclosures Ailawadhi: Novartis: Consultancy, Honoraria; Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Sher: LAM Therapeutics, Inc: Research Funding.

Objective Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship. Methods We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries. Results The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015). Conclusions We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction

Importance: Social media is widely used by various segments of society. Its role as a tool of communication by the Public Health Departments in the U.S. remains unknown. Objective: To determine the impact of the COVID-19 pandemic on social media following of the Public Health Departments of the 50 States of the U.S. Design, Setting, and Participants: Data were collected by visiting the Public Health Department web page for each social media platform. State-level demographics were collected from the U.S. Census Bureau. The Center for Disease Control and Prevention was utilized to collect information regarding the Governance of each State’s Public Health Department. Health rankings were collected from “America’s Health Rankings” 2019 Annual report from the United Health Foundation. The U.S. News and World Report Education Rankings were utilized to provide information regarding the public education of each State. Exposure: Data were pulled on 3 separate dates: first on March 5th (baseline and pre-national emergency declaration (NED) for COVID-19), March 18th (week following NED), and March 25th (2 weeks after NED). In addition, a variable identifying the total change across platforms was also created. All data were collected at the State level. Main Outcome: Overall, the social media following of the state Public Health Departments was very low. There was a significant increase in the public interest in following the Public Health Departments during the early phase of the COVID-19 pandemic. Results: With the declaration of National Emergency, there was a 150% increase in overall public following of the State Public Health Departments in the U.S. The increase was most noted in the Midwest and South regions of the U.S. The overall following in the pandemic “hotspots,” such as New York, California, and Florida, was significantly lower. Interesting correlations were noted between various demographic variables, health, and education ranking of the States and the social media following of their Health Departments. Conclusion and Relevance: Social media following of Public Health Departments across all States of the U.S. was very low. Though, the social media following significantly increased during the early course of the COVID-19 pandemic, but it still remains low. Significant opportunity exists for Public Health Departments to improve social media use to engage the public better.

Background: Clinical trials are critical to drug development and the formulation of evidence-based guidelines which are essential to providing crucial and often life-saving treatment to cancer patients. Clinical trial participation is very poor in the United States overall, with a dismal representation of racial minorities. While this has been a focus of several efforts focused on education, targeted enrollment etc., there is a lack of understanding of the patient's knowledge and preferences, and how that may be shaping their decision to consider participation in clinical trials. We undertook a patient-reported survey to explore these factors and understand any underlying disparities. Methods: A 15-question paper-based anonymous questionnaire addressing the cancer patient's knowledge about their disease and clinical trials, as well as factors that may shape their understanding of, or may be barriers to their participation in clinical trials was used. This was administered to adult patients with lymphoid malignancies at the Mayo Clinic in Florida. Categorical and continuous variables between white and minority respondents were compared using the Chi-square test and U Mann Whitney with a significance level of 0.05. Results: The survey was completed by 203 cancer patients. Of these, 3 patients did not report race and ethnicity and so responses from 200 patients were included in the final analysis. Of the respondents, 73% (n=146) were white and 27% (n=54) were minorities. Whites were older than minorities, although not statistically significant (median 67 vs. 61.5 yrs, p=0.06). Minority patients had lower education level with 41% having ≤high school education as compared to 16% whites (p<0.001). Majority of white patients (53%) reported their physicians as the highest ranked source of information for cancer vs. 33% minority patients (p=0.01). Other sources of information explored were internet, nurses, family/friends, books/flyers or other patients. A higher number of white patients reported treatment and its side effects to be the topic of most importance to them at the time of cancer diagnosis as compared to minorities (33% vs. 15%, p=0.01). Similarly, prognosis was more important for a higher number of whites than minorities (21% vs. 15%, p=0.03). Understanding of the diagnosis and financial impact were also explored but not found to have any significant difference. Understanding their treatment and long-term treatment plan was the most frequent knowledge gap reported by whites (81%) vs. minorities (54%, p=0.004). Minorities had several knowledge gap areas (understanding the diagnosis, treatment, side effects, long-term treatment plan, financial impact, survival) more evenly distributed. Regarding clinical trials, minorities were more likely to agree that clinical trials were of benefit for patients (42% vs. 28%, p=0.05) and that in a clinical trial the experimental drug always works better than the one it is being compared to (65% vs. 38%, p<0.001). Minority patients were less likely to agree to participating in clinical trials just based on their doctor's recommendation and judgement (83% vs. 93%, p=0.03). A higher number of minority patients felt that pharmaceutical companies have a big influence on the result of a clinical trial (83% vs. 65%, p=0.01). Fear of not benefiting from clinical trials was the reason for not participating among a higher number of whites (36% vs. 19%, p=0.02) while minorities more frequently reported fear of being a guinea pig (22% vs. 14%) and fear of financial burden (17% vs. 8%) although these were not statistically significant. Conclusions: Racial disparities exist at various aspects of cancer-related knowledge resources, gaps and needs. Minorities have more widespread knowledge gaps and depend on more resources for cancer-related knowledge, which may affect their clinical trial participation and preferences. There appears to be mistrust and misinformation guiding minority patient's understanding, leading to more widespread fears of clinical trials. Knowledge gaps and misinformation needs to be addressed in order to achieve higher participation in clinical trials in general, and among minority patients in particular. Disclosures Manochakian: AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Guardant health: Membership on an entity's Board of Directors or advisory committees; Novocure: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. 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.

Introduction Multiple myeloma (MM), relapsed or refractory (R/R) to standard of care therapies, represents a treatment indication with a significant unmet clinical need. Transcriptional activation of c-MYC through bromodomain and extra-terminal (BET) proteins contributes to the malignant phenotype of the disease. RO is a novel thienodiazepine, small molecule, non-covalent inhibitor of the BET family of bromodomains. Preclinical studies with BET inhibitors have demonstrated significant single agent in vivo activity in myeloma, accompanied by down-regulation of MYC and MYC target gene expression. We report results of a monotherapy phase 1b study of RO in R/R MM (NCT03068351). Methods Eligible pts with R/R MM included those treated with at least three prior lines of multiple myeloma therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent. Primary refractory myeloma pts were only allowed in the dose escalation portion of the study. In the dose escalation (part I), pts received subcutaneous (SC) escalating doses of RO (0.30-0.65 mg/kg) in a standard 3 + 3 design on days 1 - 14 of 21-day cycles to determine both the maximum tolerated dose (MTD) and recommended dose (RD). In the expansion cohort (part II), pts received RO as monotherapy at the RD level. Primary endpoint was safety (DLT, MTD, RD) and secondary endpoints included evaluation of pharmacodynamics (CD11b expression) and preliminary efficacy assessments based on IMWG criteria. Results Between June 2017 and April 2019, a total of 24 pts were enrolled in the US, the UK and Australia. 13 pts were enrolled in the dose escalation and 11 pts in the expansion part. The median age of pts was 65.5 years (range: 46 - 82 years). The study population was heavily pretreated with a median of 6 (3-9) prior therapies. Pts were refractory to immunomodulatory drugs (63%), proteasome inhibitors (46%), both (46%), or daratumumab (42%). 57 total cycles were administered, with a median of 2 (1-6) cycles per patient (pt). Two DLTs occurred in one pt in the 0.65 mg/kg cohort (thrombocytopenia grade 4, angina pectoris grade 3). The recommended dose is 0.65 mg/kg. Grade 3 treatment emergent AEs in ≥ 5% of pts were thrombocytopenia (11 pts [45.8%]), anemia (7 pts [29.2%]), fatigue (3 pts [12.5%]), injection site reaction, malaise, decreased appetite, and hyponatremia (2 pts [8.3%] each). 3 pts (12.5%) experienced a total of 4 AEs leading to discontinuation of the study treatment; these AEs were left ventricular dysfunction, fatigue, sepsis, and staphylococcal bacteremia (the latter two AEs occurred in the same pt). A total of 8 deaths (33.3%) were reported in the study, all as a consequence of progressive disease. The best overall response recorded was partial response in 4 pts (16.7 %), 3 of whom having received prior daratumumab. One pt experienced a minimal response, and stable disease was reported in 12 out of 24 (50%). There was no evidence for a dose-related increase in efficacy, though data are very limited (Table). Responses obtained during treatment with RO6870810 were short-lived and lasted for appr. 6 weeks. As evidence of target engagement, pharmacodynamic profiling demonstrated decreases in CD11b levels in peripheral blood mononuclear cells (Figure). Conclusions Treatment of MM pts with the BET inhibitor RO as monotherapy resulted in a high incidence of cytopenias, especially grade 3-4 thrombocytopenia and grade 3 anemia. However, none of these events led to study drug discontinuation. Cytopenias are a known side effect of BET inhibitors, with thrombocytopenia frequently reported as a DLT in various pt populations. Pts with NUT carcinoma, other solid tumors, or diffuse large B-cell lymphoma treated in the First in Man trial of RO had a low rate of cytopenias, indicating that the underlying disease and the extensive pre-treatment in MM may play a role in their occurrence (publication submitted). In this heavily pretreated R/R MM population, we have established 0.65 mg/kg as the recommended monotherapy dose. Pharmacodynamics effects were evident at this dose, but as monotherapy in this R/R MM cohort, response rates were low and less durable. Future drug combination approaches may result in an improved benefit / risk ratio. Disclosures Ramasamy: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria. Nooka:Adaptive Technologies: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding. Quach:Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding. Htut:City of Hope Medical Center: Current Employment. Popat:AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Liedtke:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees. Tuchman:Caelum: Honoraria; Sanofi: Honoraria, Research Funding; Amgen: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Roche: Research Funding; Karyopharm: Honoraria, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau. Hertzberg:Gilead: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; Takeda: 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; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Demario:BioNTech SE: Current Employment, Current equity holder in publicly-traded company; Hoffmann-La Roche Ltd.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Nueesch:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Chesne:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Franjkovic:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Lechner:Roche Diagnostics GmbH: Current Employment, Current equity holder in publicly-traded company. Kornacker:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company.

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: 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.