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Introduction Immunomodulatory drugs (IMiDs), particularly lenalidomide, are associated with adverse skin reactions most commonly rash, xeroderma, and pruritus. While multiple myeloma disproportionately impacts black patients, the clinical trials used for registration of these medications predominantly enrolled white patients. The incidence and severity of skin pigment changes in black patients are therefore not known. Hyperpigmentation can be a highly visible and distressing side effect leading to noncompliance. Methods This retrospective study evaluated all patients treated with thalidomide, lenalidomide or pomalidomide from January 2013 to March 2020 across all indications at Boston Medical Center. An internally developed survey consisting of 14-questions was mailed to all patients identified through prescriptions written in the electronic medical record (Epic). The survey questions included ethnicity and race identification and whether skin changes, particularly hyperpigmentation, occurred during treatment. For those patients with skin changes, follow-up questions asked about the nature of the skin change, pattern, location and duration. Distress related to skin changes was reported on a scale of 1 to 10; 1 being minimal distress and 10 being maximal distress. Photographs were requested (if available) before, during and after IMiD therapy. Results A total of 214 patients were identified who were prescribed thalidomide (4, 1.9%), lenalidomide (204, 95.3%) or pomalidomide (81, 37.9%). Of the 214 surveys, 106 (49.5%) were completed and all of the responses were included in statistical analysis. Of the 106 patients, 49 (46.2%) identified as black/African American and 57 (53.8%) reported being non-black (Asian, Hispanic or Latino, American Indian/Alaskan Native, White, Native Hawaiian/Other Pacific Islander or other). Skin changes were reported by 27 (25.5%) of the patients who completed surveys. Consistency and description of the skin changes can be found in Table 1. Hyperpigmentation (skin darkening), specifically, was reported by 20 (40.8%) of the black/African American patients and 2 (3.5%) of the non-black patients. The most commonly reported location of hyperpigmentation was on the palms and soles (15, 68.2%), forearms (7, 31.8%) and face (6, 27.3%). Onset began within 3 months of starting therapy in 10 (45.5%) of these patients. Of the 11 patients who are no longer on IMiD therapy, 4 (36.6%) had full resolution of skin changes, 5 (45.5%) noted partial resolution, and 2 (18.2%) had no improvement. The reported distress score ranged from 1-9 (median 5). Photographs of typical skin hyperpigmentation will be included at conference presentation. Conclusion Skin hyperpigmentation due to IMiD therapy is commonly seen in black/African American patients. Specifically, hyperpigmentation is 11.6 times more likely to occur in black/African American patients as compared to all other races. In these patients, hyperpigmentation is most noticeable on the palms, face and soles of the feet. These changes typically occur early in the course of therapy and do not completely reverse, even long after drug cessation. It is important for providers to discuss the possibility of these skin changes when using IMiDs in this patient population. Download : Download high-res image (378KB) Download : Download full-size image Disclosures Blevins: Epizyme: Other: Focus Group. Hughes: Karyopharm: Speakers Bureau; Abbvie: Speakers Bureau; Amgen: Speakers Bureau; Rigel: Other: advisory board. Sarosiek: Spectrum: Research Funding. Sanchorawala: UpToDate: Patents & Royalties; Abbvie: Other: advisory board; Proclara: Other: advisory board; Caleum: Other: advisory board; Regeneron: Other: advisory board; Oncopeptide: Research Funding; Caelum: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Sloan: Abbvie: Consultancy; Stemline: Consultancy.

Introduction Intravenous (IV) daratumumab has become a standard in the treatment of MM and AL amyloidosis largely due to its significant clinical benefit. Due to the high risk of infusion-related reactions (IRRs), it is associated with prolonged infusion times. These lengthy administrations can limit clinic capacity, require split dose infusions, increase chair time, decrease patient satisfaction, and create access barriers in the era of COVID-19. Recently, a fixed-dose subcutaneous (SC) formulation of daratumumab was approved for the treatment of MM, and the safety-run in results (N=28 patients) from a phase III, randomized trial in AL amyloidosis using the SC formulation were published. The SC formulation has the potential to mitigate some of the setbacks from IV formulation and help improve efficiency in the era of COVID-19, where most clinics are faced with limiting and spreading out volume due to space constraints and social distancing requirements. We present real world evidence from a large academic center's experience with adoption of SC formulation to help overcome current challenges. Methods We prospectively reviewed all patients being treated with IV daratumumab for MM and/or AL amyloidosis at Boston Medical Center Health System (a 500+ bed integrated delivery network) that would be candidates for the SC formulation. A protocol was designed to switch patients that were currently on IV daratumumab as well as patients newly initiating daratumumab to the SC formulation. Patients deemed eligible were switched to the SC formulation under pharmacy benefit (pending insurance authorization by a pharmacy liaison) at their next scheduled infusion visit. Rationale for switching patients to pharmacy benefit was to support home administration during future surge from COVID-19, using our specialty pharmacy travel RN program. Patients that were naïve to daratumumab, started their first dose as a SC injection. Patients were monitored for 30 minutes following the first SC dose and were pre-medicated with oral acetaminophen, dexamethasone, and diphenhydramine. Patient and nursing satisfaction were assessed after switching to SC daratumumab, using internally developed surveys. Using wholesale acquisition cost, cost analysis was performed between the two formulations. Infusion chair time, improvement in clinic efficiency (using our standard infusion time of 90 minutes for IV daratumumab infusions after the 2nd dose), and safety were assessed and compared. Results A total of 26 patients were treated with daratumumab for MM and AL amyloidosis from June 1, 2020 to August 1, 2020. 85% (22/26) of patients were administered the SC formulation. Of these 22 patients, 68% of patients were switched from the IV formulation (15/22) and 32% (7/22) were naïve to daratumumab. The majority (14/22) of SC administrations were patients receiving daratumumab monotherapy for relapsed MM. A breakdown of patient regimens and insurance type is seen in table 1. IRRs were reported in 0 patients starting [or transitioning to] SC daratumumab. Injection site reactions were not reported in any patient. One patient had facial and neck swelling 2 days after administration of SC daratumumab (with no other symptoms) but resolved within 24 hours of an additional dose of dexamethasone and did not recur upon re-challenge of SC daratumumab. Severe neutropenia (ANC less than 500) was reported in 9% of patients (2/22), both patients in the group naïve to daratumumab. Febrile neutropenia was not seen. One patient was being treated with concomitant pomalidomide and the second was treated with lenalidomide and had a baseline ANC of 500 prior to initiation of therapy. Adoption of SC daratumumab led to elimination of 133 hours of chair time and nursing time, or 1260 hours annualized for the year. Cost savings with the elimination of nursing time translates to approximately $100,000 to the institution and approximately $230,000 to the payer. The results compiled from patient and nursing satisfaction surveys are being analyzed and will be presented. Conclusion We report a successful conversion and adoption of SC daratumumab at our ambulatory hematology/oncology clinic. Insurance authorization does not appear to limit the adoption of this therapy in clinic irrespective of diagnosis or regimen used. Furthermore, the reduction in chair time and patient convenience was largely beneficial in light of COVID-19 to minimize patient exposure in clinic. Disclosures Hughes: Rigel: Other: advisory board; Abbvie: Speakers Bureau; Amgen: Speakers Bureau; Karyopharm: Speakers Bureau. Blevins:Epizyme: Other: Focus Group. Sarosiek:Spectrum: Research Funding. Sloan:Abbvie: Consultancy; Stemline: Consultancy. Sanchorawala:Celgene: Research Funding; Takeda: Research Funding; Caleum: Other: advisory board; Proclara: Other: advisory board; Regeneron: Other: advisory board; Abbvie: Other: advisory board; Janssen: Research Funding; UpToDate: Patents & Royalties; Oncopeptide: Research Funding; Prothena: Research Funding; Caelum: Research Funding.

Introduction Intravenous (IV) daratumumab has become a standard in the treatment of MM and AL amyloidosis largely due to its significant clinical benefit. Due to the high risk of infusion-related reactions (IRRs) prolonged infusion times are required at time of treatment initiation. These lengthy administrations can limit clinic capacity, require split dose infusions, increase chair time, and decrease patient satisfaction. Fixed-dose subcutaneous (SC) formulation of daratumumab (daratumumab and hyaluronidase-fihj) was approved in 2020 for the treatment of MM and subsequently, AL amyloidosis in 2021. While landmark trials have demonstrated its efficacy, there is lack of consensus around the standardized pre-medications and post-injection monitoring times for SC daratumumab. We present real world evidence from a large academic center with adoption and standardization of SC formulation of daratumumab into clinical practice. Methods We evaluated all patients that received SC daratumumab for MM and/or AL amyloidosis at Boston Medical Center from June 1, 2020 to February 28, 2021. Baseline demographics were collected, including patient diagnosis, chemotherapy regimen, prior daratumumab administration details, and total doses of daratumumab received. Patients that were naïve to daratumumab, started their first dose as a SC injection. Patients were monitored for 30 minutes following the first SC dose and were pre-medicated with all oral agents: acetaminophen, dexamethasone, and diphenhydramine. Infusion chair time, improvement in clinic efficiency (using our standard infusion time of 90 minutes for IV daratumumab infusions after the 2nd dose), and safety were evaluated. Results A total of 41 patients were treated with SC daratumumab. Eighteen patients (44%) were switched from IV daratumumab to SC daratumumab. All other patients were naïve to SC daratumumab (n=23). All patients were monitored for 30 minutes after their first SC daratumumab dose only. In the absence of an ARR (administration-related reactions), patients were not monitored after subsequent injections. One patient had facial and neck swelling 2 days after administration of SC daratumumab (with no other symptoms) but resolved within 24 hours of an additional dose of dexamethasone and did not recur upon re-challenge of SC daratumumab. One patient experienced nausea following her first dose of SC daratumumab but it resolved without intervention. All patients received dexamethasone 20-40 mg (as anti-myeloma dose), acetaminophen 650 mg, and diphenhydramine 25-50 mg prior to the dose of SC daratumumab. Fourteen patients (24%) received montelukast 10 mg and 19 patients (46%) received famotidine 20-40 mg prior to the dose of SC daratumumab at provider discretion. Dexamethasone 4 mg daily for two days post-injection was not administered with SC formulation as was previously routine with the IV formulation. When analyzing the chair time saved by this standard monitoring protocol, a total of 478.8 hours of chair time were saved that were used for other patients in our practice (average of 11.7 hours saved per patient). Conclusion We report a successful conversion and adoption of SC daratumumab at our ambulatory hematology/oncology clinic. A standard 30-minute monitoring parameter can safely be implemented following the first SC daratumumab dose. Furthermore, less aggressive supportive medications can also be used. Integration of the SC formulation yielded significant chair time savings and may have the ability to create a more efficient clinic workflow. Figure 1 Figure 1. Disclosures Hughes: Rigel: Other: Advisory Board, Research Funding; Amgen: Speakers Bureau; Karyopharm: Other: Advisory Board, Speakers Bureau; Abbvie: Speakers Bureau. Sloan: Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Stemline: Honoraria. Sanchorawala: Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Pfizer: Honoraria.

Introduction Immunomodulatory drugs (IMiDs), particularly lenalidomide, are associated with adverse skin reactions most commonly rash, xeroderma, and pruritus. While multiple myeloma disproportionately impacts black patients, the clinical trials used for registration of these medications predominantly enrolled white patients. The incidence and severity of skin pigment changes in black patients are therefore not known. Hyperpigmentation can be a highly visible and distressing side effect leading to noncompliance. Methods This retrospective study evaluated all patients treated with thalidomide, lenalidomide or pomalidomide from January 2013 to March 2020 across all indications at Boston Medical Center. An internally developed survey consisting of 14-questions was mailed to all patients identified through prescriptions written in the electronic medical record (Epic). The survey questions included ethnicity and race identification and whether skin changes, particularly hyperpigmentation, occurred during treatment. For those patients with skin changes, follow-up questions asked about the nature of the skin change, pattern, location and duration. Distress related to skin changes was reported on a scale of 1 to 10; 1 being minimal distress and 10 being maximal distress. Photographs were requested (if available) before, during and after IMiD therapy. Results A total of 214 patients were identified who were prescribed thalidomide (4, 1.9%), lenalidomide (204, 95.3%) or pomalidomide (81, 37.9%). Of the 214 surveys, 106 (49.5%) were completed and all of the responses were included in statistical analysis. Of the 106 patients, 49 (46.2%) identified as black/African American and 57 (53.8%) reported being non-black (Asian, Hispanic or Latino, American Indian/Alaskan Native, White, Native Hawaiian/Other Pacific Islander or other). Skin changes were reported by 27 (25.5%) of the patients who completed surveys. Consistency and description of the skin changes can be found in Table 1. Hyperpigmentation (skin darkening), specifically, was reported by 20 (40.8%) of the black/African American patients and 2 (3.5%) of the non-black patients. The most commonly reported location of hyperpigmentation was on the palms and soles (15, 68.2%), forearms (7, 31.8%) and face (6, 27.3%). Onset began within 3 months of starting therapy in 10 (45.5%) of these patients. Of the 11 patients who are no longer on IMiD therapy, 4 (36.6%) had full resolution of skin changes, 5 (45.5%) noted partial resolution, and 2 (18.2%) had no improvement. The reported distress score ranged from 1-9 (median 5). Photographs of typical skin hyperpigmentation will be included at conference presentation. Conclusion Skin hyperpigmentation due to IMiD therapy is commonly seen in black/African American patients. Specifically, hyperpigmentation is 11.6 times more likely to occur in black/African American patients as compared to all other races. In these patients, hyperpigmentation is most noticeable on the palms, face and soles of the feet. These changes typically occur early in the course of therapy and do not completely reverse, even long after drug cessation. It is important for providers to discuss the possibility of these skin changes when using IMiDs in this patient population. Disclosures Blevins: Epizyme: Other: Focus Group. Hughes:Karyopharm: Speakers Bureau; Abbvie: Speakers Bureau; Amgen: Speakers Bureau; Rigel: Other: advisory board. Sarosiek:Spectrum: Research Funding. Sanchorawala:UpToDate: Patents & Royalties; Abbvie: Other: advisory board; Proclara: Other: advisory board; Caleum: Other: advisory board; Regeneron: Other: advisory board; Oncopeptide: Research Funding; Caelum: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Sloan:Abbvie: Consultancy; Stemline: Consultancy.

Richter syndrome (RS) is associated with poor outcome. The prognosis of patients with histologically aggressive chronic lymphocytic leukemia (CLL), or HAC, has not been studied. We aimed to correlate 2-deoxy-2-[(18)F]fluoroglucose/positron emission tomography (FDG/PET) data, histological diagnosis, clinical characteristics, and survival in patients with CLL. A total of 332 patients with CLL were histologically classified as: 95 RS, 117 HAC, and 120 histologically indolent CLL (HIC). HAC and RS patients had higher maximum standardized uptake value (SUVmax), more frequent constitutional symptoms, poorer performance status (PS), lower hemoglobin and platelets, and higher lactate dehydrogenase and β-2-microglobulin. An SUVmax ≥10 strongly correlated with mortality (overall survival [OS], 56.7 vs 6.9 months in patients with SUVmax10 vs ≥10). Survival of patients with RS and HAC was similar among patients with SUVmax10 or ≥10. SUVmax ≥10, PS ≥2, bulky disease, and age ≥65 were independently associated with shorter OS. In patients undergoing both fine-needle aspiration and biopsy, the former proved diagnostically inadequate in 23%, 29%, and 53% of HIC, HAC, and RS, respectively. FDG/PET is a useful diagnostic tool in patients with CLL and suspected transformation. Patients with HAC show different characteristics and worse prognosis compared with those with HIC. Patients with different CLL phases, but similar SUVmax have similar outcome. Tissue biopsy should be preferred for diagnosing RS.

Introduction: MAVORIC was an open-label, multicenter, randomized phase 3 study evaluating the safety and efficacy of mogamulizumab (moga) compared to vorinostat (vori) in patients with mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least one prior course of systemic therapy (NCT01728805). Primary results have been reported (Kim et al. Lancet Oncol 2018) and were based on a data cutoff date of December 31, 2016. The primary endpoint was progression-free survival (PFS); patients in the moga treatment arm experienced significantly longer PFS compared to patients in the vori treatment arm (median 7.7 months vs 3.1 months; p Methods: Patients were randomized 1:1 to moga 1.0 mg/kg administered intravenously on Days 1, 8, 15, and 22 of the first cycle and on Days 1 and 15 of subsequent cycles or vori 400 mg administered orally once daily. Patients randomized to vori were allowed to cross over to moga upon progression or intolerable toxicity. Safety was assessed by reported adverse events (AEs), changes in physical examinations, vital sign measurements, electrocardiograms, and laboratory analyses. Results: In total, 372 patients were randomized (moga, 186; vori, 186), of whom 370 received study drug and were included in the safety analysis (moga, 184; vori, 186). For the final safety analysis, median duration of follow-up was 34.5 months (range, 0.13-70.0) in the randomized part of the study. Median treatment exposure was 170 days (range, 1-1813) for moga and 84 days (4-1230) for vori, which represent the same median values but broader ranges compared to the primary analysis (primary analysis, 170 days [1-1379] for moga and 84 days [4-1058] for vori). The type and frequency of AEs in either the moga or vori treatment groups (Table) were consistent with those reported in the primary analysis. TEAEs, regardless of causality, that were reported at similar rates in the two treatment groups included constipation, peripheral edema, headache, and anemia. TEAEs (all causality) that occurred at higher frequency in the moga vs vori arm included infusion-related reaction (33.2% vs 0.5%) and drug eruption (25.0% vs 1.1%); the majority of these events were grade 1 or 2 (Table). The types and frequencies of AEs attributable to moga (per Investigator assessment) included infusion-related reaction (33.2% [61/184]), drug eruption (23.9% [44/184]), and fatigue (18.5% [34/184]), and for vori, diarrhea (55.4% [103/186]), nausea (38.2% [71/186]), and fatigue (33.3% [62/186]). In patients who crossed over from the vori to moga arm and received study drug (n=135), the most frequently reported AEs attributable to moga were infusion-related reaction (37.8% [51/135]), drug eruption (24.4% [33/135]), fatigue (7.4% [10/135]), increased alanine aminotransferase (7.4% [10/135]), and increased aspartate aminotransferase (7.4% [10/135]). Discontinuation rates due to AEs were similar between treatment arms and in crossover patients (moga, 21.7% [40/184]; vori, 23.7% [44/186]; crossover, 25.9% [35/135]). The most common AEs leading to discontinuation were drug eruption in the moga arm (7.1% [13/184]) and fatigue in the vori arm (4.3% [8/186]). Overall, the rates of drug-related serious TEAEs were similar between treatment arms and in crossover patients (moga, 19.6% [36/184]; vori, 16.7% [31/186]; crossover, 11.9% [16/135]). After the data cutoff for the primary analysis, 1 additional patient randomized to moga (decreased appetite, general physical health deterioration, hypoalbuminemia) and 1 crossover patient (cerebral hemorrhage) experienced TEAEs with an outcome of death, all considered unrelated to study treatment per Investigator. Conclusions: This final safety analysis from the MAVORIC study in patients with previously treated MF and SS demonstrates that moga was generally well tolerated. Longer follow-up and treatment exposure did not identify any new safety signals. The type and incidence of treatment-related AEs among patients receiving moga after crossover were similar to those observed for patients initially randomized to moga. Disclosures Kim: Merck: Research Funding; Portola Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon: Research Funding; Corvus: Honoraria, Membership on an entity's Board of Directors or advisory committees; Galderma: Research Funding; Elorac: Research Funding; Soligenix: Research Funding; Kyowa Hakko Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: 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; Forty Seven Inc: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medivir: Honoraria, Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; Neumedicine: Research Funding; miRagen: Research Funding. Bagot:Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Zinzani:MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Duvic:Seattle Genetics: Consultancy, Honoraria, Research Funding; Eisai: Research Funding; Shape: Research Funding; UT MD Anderson Cancer Center: Employment; USCLC Registry: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Secretary/treasurer of Item h; Spatz Foundation: Research Funding; Tetralogic: Research Funding; Millennium (formerly Takeda): Research Funding; Mallinckrodt Pharmaceuticals (formeraly Therakos, Inc): Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty Seven Inc: Membership on an entity's Board of Directors or advisory committees; Cutaneous Lymphoma Foundation: Membership on an entity's Board of Directors or advisory committees; PleXus Communications: Speakers Bureau; Guidepoint Global: Consultancy; Evidera, Inc.: Consultancy; Cell Medica Inc.: Consultancy; Allos: Research Funding; Rhizen Pharma: Research Funding; Oncoceuticals: Research Funding; Soligenetics: Research Funding; Cell Medica Ltd.: Honoraria; Therakos: Speakers Bureau; Jonathan Wood & Assoc.: Speakers Bureau; Hawaiian Dermatology Society: Speakers Bureau; Hemedicus: Speakers Bureau; Janssen Pharmaceuticals (div of Johnson & Johnson): Speakers Bureau. Morris:Guys Hospital: Employment. Kim:Medimmune: Research Funding; Soligenix: Research Funding; Kyowa Kirin: Research Funding; Galderma: Consultancy, Research Funding; Actelion: Consultancy, Research Funding. Musiek:Menlo: Other: Investigator; Helsinn: Membership on an entity's Board of Directors or advisory committees; Soligenix: Other: Investigator; Pfizer: Other: Investigator; Elorac: Other: Investigator; Kyowa: Honoraria, Other: Above honoraria: for Ad Board; miRagen: Other: Investigator. Ortiz-Romero:Actelion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kyowa: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; PLCG1: Patents & Royalties; miRagen: Membership on an entity's Board of Directors or advisory committees; MEDA: Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; 4SC: Membership on an entity's Board of Directors or advisory committees. Eradat:Kyowa: Research Funding; Kite: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Research Funding; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Research Funding. Magnolo:University Hospital of Muenster, Center of Innovative Dermatology: Employment. Scarisbrick:Kyowa Kirin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Recordat: Consultancy; 4SC: Consultancy, Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dalle:Kyowa: Other: Principal Investigator in clinical trials promoted by Kyowa. Fisher:Kyowa Kirin: Consultancy. Poligone:Stemline Therapeutics: Consultancy, Speakers Bureau; Regeneron: Consultancy, Speakers Bureau; Actelion: Consultancy, Speakers Bureau; Astex Pharmaceuticals: Research Funding; Bioniz: Research Funding; Celgene: Consultancy; Helsinn: Research Funding, Speakers Bureau; Innate Pharma: Research Funding; Kyowa Hakko Kirin: Consultancy, Honoraria, Research Funding, Speakers Bureau; miRagen: Research Funding; Soligenix: Research Funding. Pro:Takeda: Consultancy, Honoraria, Other: Travel Expenses; Celgene: Consultancy, Honoraria; Kyowa Hakka Kirin: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Quaglino:Actelion: Honoraria, Other: Advisory Board; Innate Pharma: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Kyowa Kirin: Honoraria, Other: Advisory Board; Helsinn: Honoraria, Other: Advisory Board; Therakos: Honoraria, Other: Advisory Board. Reddy:AbbVie: Honoraria; Janssen: Honoraria; KITE: Honoraria; Merck: Research Funding; Celgene: Honoraria, Speakers Bureau. Geskin:Merck: Other: Supported/Contracted Research; UpToDate: Patents & Royalties: Royalty, Receipt of Intellectual Property Rights / Patent Holder; Actelion: Other: Supported/Contracted Research; Helsinn: Consultancy, Honoraria, Other: Supported/Contracted Research; Stratpharma: Other: Supported/Contracted Research; Mallinckrodt: Consultancy, Honoraria, Other: Supported/Contracted Research; Medscape: Speakers Bureau; Medivir: Consultancy, Honoraria. Halwani:Amgen: Other: Investigator; Takeda: Other: PI; Seattle Genetics: Other: PI; Pharmacyclics: Other: Investigator; miRagen: Other: PI; Kyowa Hakko Kirin: Other: PI; Immune Design: Other: PI; Genentech, Inc.: Other: Investigator; Bristol-Myers Squibb: Other: PI; AbbVie: Other: PI. Khot:Peter MacCallum Cancer Centre: Employment; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy; Janssen: Consultancy; Kyowa Hakko Kirin: Consultancy. Korman:Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dermira: Research Funding; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Immune Pharma: 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; Kyowa: Research Funding; Leo: Research Funding; Menlo: Research Funding; Merck: Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Pfizer: Research Funding; Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rhizen: Research Funding; Sun: Honoraria, Membership on an entity's Board of Directors or advisory committees; Syntimmune: Research Funding; UCB: Research Funding; Valeant: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Horwitz:Seattle Genetics: Consultancy, Research Funding; Affimed: Consultancy; Astex: Consultancy; Portola: Consultancy; ADCT Therapeutics: Research Funding; Kyowa Hakko Kirin: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Miragen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Forty-Seven: Research Funding; Celgene: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Miragen: Consultancy; Innate Pharma: Consultancy; Kura: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Miragen: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Portola: Consultancy; Kura: Consultancy; Celgene: Consultancy, Research Funding; Kura: Consultancy; Kyowa Hakko Kirin: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Forty-Seven: Research Funding; Trillium: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy; Affimed: Consultancy; ADCT Therapeutics: Research Funding; Aileron: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin: Consultancy; Trillium: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Portola: Consultancy; Aileron: Research Funding; Mundipharma: Consultancy; Celgene: Consultancy, Research Funding; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Portola: Consultancy; Kura: Consultancy; ADCT Therapeutics: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Aileron: Research Funding; Affimed: Consultancy; Trillium: Research Funding; Innate Pharma: Consultancy; Affimed: Consultancy; Astex: Consultancy; Mundipharma: Consultancy; Aileron: Research Funding; Miragen: Consultancy; Trillium: Research Funding; Innate Pharma: Consultancy; Forty-Seven: Research Funding; Forty-Seven: Research Funding; Innate Pharma: Consultancy; Astex: Consultancy; Seattle Genetics: Consultancy, Research Funding. Lamar:Seattle Genetics: Consultancy; Kyowa: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moskowitz:Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Merck: Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Erytech Pharma: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Erytech Pharma: Consultancy; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; Cell Medica: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding. Wells:Takeda Pharmaceuticals Australia Pty Limited: Membership on an entity's Board of Directors or advisory committees; MSD Australia: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Akilov:Trillium Therapeutics: Consultancy, Other: PI on the clinical trials, Research Funding; Pfizer: Research Funding. Cowan:Kyowa Kirin: Consultancy. Dummer:Merck Sharp & Dohme: Other: Intermittent, project focused consulting and/or advisory relationships; Novartis: Other: Intermittent, project focused consulting and/or advisory relationships; Bristol-Myers Squibb: Other: Intermittent, project focused consulting and/or advisory relationships; Roche: Other: Intermittent, project focused consulting and/or advisory relationships; Amgen: Other: Intermittent, project focused consulting and/or advisory relationships; Takeda: Other: Intermittent, project focused consulting and/or advisory relationships; Pierre Fabre: Other: Intermittent, project focused consulting and/or advisory relationships; Sun Pharma: Other: Intermittent, project focused consulting and/or advisory relationships; Sanofi: Other: Intermittent, project focused consulting and/or advisory relationships; Catalym: Other: Intermittent, project focused consulting and/or advisory relationships; Second Genome: Other: Intermittent, project focused consulting and/or advisory relationships. Lechowicz:Kyowa Kirin Inc: Consultancy; Spectrum: Consultancy. Foss:Eisai: Consultancy; Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; miRagen: Consultancy; Acrotech: Consultancy; Mallinckrodt: Consultancy; Spectrum: Other: fees for non-CME/CE services . Wilcox:University of Michigan: Employment. Porcu:Innate Pharma: Honoraria, Other: Scientific Board, Research Funding; Viracta: Honoraria, Other: Scientific Board, Research Funding; BeiGene: Other: Scientific Board, Research Funding; Incyte: Research Funding; Daiichi: Research Funding; Kyowa: Honoraria, Other: Scientific Board, Research Funding; ADCT: Research Funding; Spectrum: Consultancy. Vermeer:Kyowa: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Abhyankar:Therakos: Other: Consulting, Speakers Bureau; Incyte: Speakers Bureau. Pacheco:University of Colorado: Employment. William:Techspert: Consultancy; Guidepoint Global: Consultancy; Defined Health: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Fukuhara:Kyowa-Hakko Kirin: Honoraria; Bayer: Research Funding; Mundi: Honoraria; Janssen Pharma: Honoraria; Mochida: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria; Eisai: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Nippon Shinkyaku: Honoraria; Zenyaku: Honoraria; AbbVie: Research Funding; Gilead: Research Funding; Solasia Pharma: Research Funding. Munoz:Pharmacyclics /Janssen: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Merck: Consultancy; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene/Juno: Consultancy, Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau; Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Portola: Research Funding; Incyte: Research Funding; Kite/Gilead: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy; Alexion: Consultancy; Pfizer: Consultancy. Querfeld:Elorac: Other: Investigator, Research Funding; Trillium: Consultancy, Other: Investigator, Research Funding; Medivir: Consultancy; miRagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Helsinn: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Soligenix: Other: Investigator; City of Hope Cancer Center and Beckman Research Institute: Employment; Celgene: Other: Investigator, Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Eisai: Other: Investigator; Bioniz: Membership on an entity's Board of Directors or advisory committees, Other: Investigator. Uhara:Kyowa Kirin Co., Ltd: Honoraria, Research Funding. Huen:Innate Pharmaceuticals: Research Funding; Galderma Inc: Research Funding; Rhizen Pharmaceuticals: Research Funding; Glaxo Smith Kline Inc: Research Funding. Tobinai:Meiji Seika: Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Janssen Pharmaceutical: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Ono Pharmaceutical: Consultancy, Honoraria, Research Funding; Zenyaku Kogyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Mundi Pharma: Consultancy, Honoraria, Research Funding; Eisai: Honoraria, Research Funding; HUYA Bioscience: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; AbbVie: Research Funding; Verastem: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Yakult: Honoraria; Solasia: Honoraria. Tokura:Kyowa Kirin Pharmaceutical Development, Inc.: Honoraria. Boh:Actelion: Other: Principal Investigator; Tulane University School of Medicine: Employment; Celgene: Other: Principal Investigator, Speaker, Grants; Sun: Other: Speaker; Janssen: Other: Principal Investigator, Speaker, Grants; Novartis: Other: Principal Investigator, Speaker, Grants; Soligenix: Other: Principal Investigator; Incyte: Other: Principal Investigator; Regeneron: Other: Principal Investigator, Grants; Ortho Dermatologics: Other: Speaker, Grants; Pfizer: Other: Principal Investigator; UCB: Other: Speaker, Grants; Elorac: Other: Principal Investigator; Abbvie: Other: Principal Investigator. Nicolay:Teva Pharmaceutical Industries: Honoraria, Other: Conference participation fees; Novartis AG: Consultancy, Honoraria; Biogen GmbH: Consultancy, Honoraria; Almirall Hermal AG: Consultancy, Honoraria; Actelion Pharmaceuticals: Consultancy, Honoraria; Innate Pharma: Consultancy; Kyowa Hakko Kirin: Consultancy, Honoraria; Takeda Pharmaceuticals: Consultancy. Leoni:Kyowa Kirin Pharmaceutical Development, Inc.: Employment. Ito:Kyowa Kirin Pharmaceutical Development, Inc.: Employment. Herr:Kyowa Kirin, Inc.: Employment. Sokol:EUSA: Consultancy.

Introduction Fostamatinib is a first in its class oral inhibitor of spleen tyrosine kinase (Syk) pathway for treatment of adults with immune thrombocytopenia (ITP) with insufficient response to previous treatment. Choice of treatment for relapsed ITP varies greatly according to clinician and patient preference. It is common for patients to switch between available thrombopoietin (TPO) agonists and now fostamatinib. Titration of these agents is often cumbersome and labor intensive; romiplostim in particular requires weekly visits with lab draws and consumes nurse, pharmacy and provider effort. Here we present real world experience with fostamatinib use in an academic medical center. Methods. We retrospectively identified four patients who were prescribed fostamatinib within the past nine months at Boston Medical Center Health System. All patients had a diagnosis of chronic ITP and were previously treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. With respect to previous TPO receptor use, two of four patients had received both eltrombopag and romiplostim. Patients were started on fostamatinib at a dose of 100 mg by mouth twice daily and titrated up to 150 mg by mouth twice daily if platelet counts were Results. Three of four patients initiated on fostamatinib had a baseline platelet count 100K or greater and the fourth patient had ITP refractory to multiple lines of therapy with a baseline platelet count of 7K at therapy initiation. Three patients sought alternative therapy given side effects from TPO agonists or inconvenience of romiplostim. Three patients had platelets counts >50K at 4 weeks and one patient had a platelet count Conclusion. The ideal place in therapy for fostamatinib in ITP therapy is not yet clear. However, the availability as an oral option for patients with refractory disease is appealing. One of our patients required rescue therapy which should be considered when transitioning patients to fostamatinib from TPO agonists. Additionally, side effect management with anti-hypertensives and anti-diarrheal agents may be required to continue therapy. Effectiveness of romiplostim may predict responsiveness to fostamatinib, although additional data are needed. Table Disclosures Shah: Rigel Pharmaceutical: Consultancy, Speakers Bureau. Sarosiek:Acrotech: Research Funding. Sloan:Merck: Other: endpoint review commitee; Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy.

Background: It is estimated that the U.S. will spend $370 billion in 2019 on pharmaceuticals and by 2020 the cost of cancer care will be approximately 158 billion. Cost containment strategies for high cost drugs are needed. In 2019 global sales from subcutaneous (SubQ) bortezomib manufactured by Takeda® will exceed $1 billion. There exists an opportunity to decrease overall cost related to bortezomib by $300-400 million across the globe by switching patients to bortezomib intravenous (IV) (manufactured by Fresenius Kabi®). Generic bortezomib was first approved by the FDA in January 2018 but it can only be administered intravenously. A phase 3 randomized controlled trial of twice weekly SubQ vs IV bortezomib showed no difference in time to progression or 1 year overall survival, however rate of Grade 3 peripheral neuropathy doubled in the IV arm compared to SubQ (Moreau et al, 2011). Although twice weekly bortezomib has fallen out of favor and there are retrospective data suggesting that neuropathy from weekly subQ and weekly IV bortezomib may be similar, there exist no prospective data to date to confirm this. Bortezomib induced peripheral neuropathy (BIPN) typically occurs by cycle 4 of twice weekly therapy, and the majority of cases are partially reversible (Dimopolous et al, 2011). We hypothesized that patients who have not developed neuropathy after or during 4 cycles of subcutaneous bortezomib could be switched to IV bortezomib without greatly increasing neuropathy. Methods: Boston Medical Center Health System is a 500 plus bed integrated delivery network which not only functions as payer but also as a provider. A protocol was implemented to switch patients from SubQ to IV bortezomib. Patients had to complete 4 cycles of SubQ bortezomib and have either Grade 1 or no BIPN to qualify to switch to IV bortezomib generic formulation. Patients were eligible to be switched regardless of indication or dose, if other criteria were met. After approval from the hematology/oncology providers and nursing department, this protocol was implemented to start accrual in November 2018. Patients eligible for the switch were identified primarily by pharmacists. After provider approval, pharmacists would update the treatment plan orders and also notify nursing and patients of the change. Nursing and patient satisfaction surveys were also administered to obtain input from all stakeholders. Results: Eleven patients have received at least 1 cycle of IV generic bortezomib for various indications from Nov 2018 to June 2019, with minimum of 2 doses and maximum of 16 doses. The diseases for which bortezomib was being used included multiple myeloma (n= 6) and AL amyloidosis (n= 2), renal transplant rejection and thrombotic thrombocytopenic purpura (TTP). One of the 11 patients had Grade 1 BIPN prior to switching, while all others reported no neuropathy prior to the switch. None of the patients have developed new neuropathy after making the switch from subQ to IV bortezomib. Results of the nursing and patient satisfaction surveys are being collected and will be presented. Conclusion: We describe a method to switch from subcutaneous bortezomib to generic IV bortezomib instituted at a large academic medical center as a cost containment strategy. This has resulted in no new cases of neuropathy in our growing data set. Global adoption of this protocol has the potential to substantially reduce drug costs related to multiple myeloma. Disclosures Sanchorawala: Celgene: Research Funding; Takeda: Research Funding; Proclara: Consultancy, Honoraria; Caelum: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Prothena: Research Funding. Sloan:Merck: Other: endpoint review commitee; Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy. Sarosiek:Acrotech: Research Funding. Shah:Rigel Pharmaceutical: Consultancy, Speakers Bureau.

Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population.

Background: Outcomes in multiple myeloma (MM) have improved in recent years, but disparities among racial-ethnic groups persist (Costa, 2017; Ailawadhi, 2012; Waxman, 2010). Differences in disease biology, treatment modalities, and access to care are likely explanations for these disparities. Currently the preferred induction therapy for MM is a three-drug regimen, such as bortezomib/cyclophosphamide/dexamethasone (VCD), bortezomib/lenalidomide/dexamethasone (VRD) or carfilzomib/pomalidomide/dexamethasone (KPd). This is often followed by high-dose melphalan with autologous stem cell transplant (HDM/SCT) and maintenance therapy. Older or frail adults may not tolerate this three-drug approach or HDM/SCT. Two-drug regimens without HDM/SCT are acceptable options in these groups. This retrospective study was designed to explore the utilization of preferred induction therapy and HDM/SCT across racial-ethnic groups at Boston Medical Center. Results: One hundred sixty-eight patients with MM were treated at our institution between 2004 and 2017. Sixty-six percent were non-Hispanic Black (NHB), 20% were non-Hispanic White (NHW), and 14% were Hispanic. The average age was 63 years and 56% of the population was male. There was no significant difference in age or sex between the NHB, NHW, and Hispanic groups. Only 83 patients (49%) received a three-drug induction regimen. Forty-six (51%) were < 65 years old, while 37 (48%) were ≥ 65 years old. The utilization of standard induction therapy was significantly different among racial-ethnic groups < 65 years old. Thirteen NHW patients (76%) received triplet induction therapy, compared to only 10 Hispanics (63%) and 23 NHB patients (40%) (p=0.02). A similar trend was observed in regards to treatment with HDM/SCT within the first year after diagnosis for patients age < 65 years and triplet therapy in patients undergoing HDM/SCT (any age), although these trends did not reach statistical significance (47% NHWs, 31% Hispanics, and 28% NHBs, p=0.31 and 91% NHWs, 78% Hispanics, and 58% NHBs, p=0.11 respectively). There were no significant differences among groups age ≥ 65 years in regards to triplet induction therapy, HDM/SCT within the first year, or HDM/SCT any time after diagnosis. The median time to HDM/SCT and overall survival were not significantly different between racial-ethnic groups, regardless of age above or below 65 years. Conclusion: NHB and Hispanic patients less than 65 years old are less likely to receive a standard three-drug induction regimen. There is also a trend towards fewer patients receiving HDM/SCT in the first year after diagnosis among these groups compared to NHW patients. Our study did not confirm a survival benefit in NHB patients under age 65, which has been reported in prior studies (Fillmore, 2018; Waxman, 2010). The lack of benefit seen in this study could be related to lower rates of three-drug induction therapy and HDM/SCT in the NHB group. Further research is needed to explore patient co-morbidities, socioeconomic factors, and physician biases to determine why minority groups have less utilization of standard therapies. Table. Table. Disclosures No relevant conflicts of interest to declare.

Background: Financial hardship is the combined effect of medical expenditures, out of pocket expenses, and the impact of a cancer diagnosis and treatment on work. Productivity loss is a measure of work engagement, specifically missed time and/or altered performance, experienced by parent caregivers of children with cancer in the form of missed time from work and/or altered performance at work. Health-related quality of life (HRQL) is an important indicator of the disease process and its functional consequences among children at the time of initial diagnosis with cancer. The association of parental productivity loss with the child's HRQL is unknown. Methods: Two hundred ninety-one parent caregivers of children and adolescents, ages 5-17.9 years with newly diagnosed advanced stage Hodgkin Lymphoma (HL) were invited to participate in a study to assess costs of care as part of a larger Children's Oncology Group Phase III trial. Consenting parents completed the Caregiver Work Limitations Questionnaire (CG WLQ) and the Child Health Ratings Inventories (CHRIs)-Global Health measure prior to start of therapy. The CG WLQ is a validated 23-item measure, which quantifies the percent of time respondents had difficulty performing four key dimensions of work because of caregiving: physical tasks, mental-interpersonal tasks, output tasks, and time management. Mean scale scores (SD), ranging from 0-100, indicate the percentage of time the respondent reported work limitations by dimension in the month prior to diagnosis. The estimated productivity loss score, expressed as a percentage of time, is calculated from the weighted sum of the four scale scores, using an established algorithm validated in the generic WLQ. This is then monetized by multiplying the productivity loss score by the national average wage index of $50,000. The 10-item CHRIs-Global is a parent-proxy report of child HRQL and yields scores that range from 0-100, with higher scores indicating better HRQL. To describe how CG WLQ varied by child global HRQL, CG WLQ scores were reported separately for the lowest quartile of HRQL scores (Q1) and quartiles 2-4 combined (Q2-4). Mean (SD) productivity loss scores were compared using the two-sample t-test. Results: Two hundred eighty-two parents of trial participants (282/291, 97%) completed any baseline measures. Of the 242 parents who initiated the CG WLQ, 159 (66%) reported working at a paying job and were eligible to complete the remainder of the measure. The average age (SD) of caregiver respondents was 43.8 (6.9) years with 75.3% female, 74.7% White and 63.7% with at least some college education. The average age of the child with HL was 15 (2.8) years and 55% were male. The mean HRQL score was 65.2 (21.9). On average CG WLQ scores indicated that the caregiving role resulted in disrupted work tasks at least 31.4% (27.6) of the time (Table). The average percent of time that caregiving disrupted mental-interpersonal tasks, output tasks, and time management was higher in working caregivers of children with HRQL scores in the lowest quartile compared to higher quartiles. The productivity loss score was higher for caregivers whose children had lower HRQL, resulting in larger annual productivity costs. Conclusions: Family caregivers of child and adolescent HL patients are vulnerable to productivity loss, which is costly to the families, employers and the nation. High productivity losses noted at initial diagnosis indicate that financial hardship begins prior to the start of cancer treatment. Provider understanding of the association of the child's HRQL on the caregiver's work will inform strategies to maximize adherence to intensive chemotherapy and improve patients' HRQL. Disclosures Parsons: Seattle Genetics: Research Funding. Henderson:Seattle Genetics: Research Funding.

To determine the clinical fate of patients with de novo deletion 17p13.1 (17p−) chronic lymphocytic leukemia (CLL), we retrospectively studied the outcome of 99 treatment-naive 17p− CLL patients from the M. D. Anderson Cancer Center (n = 64) and the Mayo Clinic (n = 35). Among 67 asymptomatic patients followed for progression, 53% developed CLL requiring treatment over 3 years. Patients who had not progressed by 18 months subsequently had stable disease, with 3 of 19 patients progressing after follow-up of up to 70 months. Risk factors for progressive disease were Rai stage of 1 or higher and unmutated immunoglobulin variable region heavy chain (IgVH). The overall survival rate was 65% at 3 years. Rai stage 1 or higher, unmutated IgVH, and 17p− in 25% or more of nuclei were adverse factors for survival. The 3-year survival rates of patients with 1 or fewer, 2, and 3 of these factors were 95%, 74%, and 22%, respectively (P < .001). Response rates to therapy with rituximab (n = 6); purine analogues and rituximab (n = 25); and purine analogues, rituximab, and alemtuzumab (n = 16) combinations were 50%, 72%, and 81%, respectively. Patients with 17p− CLL exhibit clinical heterogeneity, with some patients experiencing an indolent course. Survival can be predicted using clinical and biologic characteristics.

The clinical course for patients with chronic lymphocytic leukemia is extremely heterogeneous. The Rai and Binet staging systems have been used to risk-stratify patients; most patients present with early-stage disease. We evaluated a group of previously untreated patients with chronic lymphocytic leukemia (CLL) at initial presentation to University of Texas M. D. Anderson Cancer Center to identify independent characteristics that predict for overall survival. Clinical and routine laboratory characteristics for 1674 previously untreated patients who presented for evaluation of CLL from 1981 to 2004 were included. Univariate and multivariate analyses identified several patient characteristics at presentation that predicted for overall survival in previously untreated patients with CLL. A multivariate Cox proportional hazards model was developed, including the following independent characteristics: age, β-2 microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved lymph node groups. Inclusion of patients from a single institution and the proportion of patients younger than 65 years may limit this model. A weighted prognostic model, or nomogram, predictive for overall survival was constructed using these 6 characteristics for 5- and 10-year survival probability and estimated median survival time. This prognostic model may help patients and clinicians in clinical decision making as well as in clinical research and clinical trial design.

Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (

Theophylline, a drug known to inhibit several classes of adenosine 3′5′ cyclic monophosphate (cAMP) phosphodiesterases (PDEs), induces apoptosis in chronic lymphocytic leukemia (CLL) cells. Because the PDE target for theophylline in CLL remains unknown, we examined the ability of isoform-specific PDE inhibitors to increase cAMP levels and induce apoptosis in primary CLL cells. Reverse transcriptase-polymerase chain reaction of purified CLL cDNA amplified transcripts for PDE1B, 4A and 4B. The type 4 PDE inhibitor rolipram but not the type 1 inhibitor vinpocetine increased CLL cAMP levels. Rolipram-inhibitable (type 4) but not calcium-calmodulin augmented (type 1) PDE enzyme activity was detected in CLL samples. In samples from 13 of 14 CLL patients, rolipram induced apoptosis in a dose-dependent fashion over a 48-hour period. Interleukin-2 (IL-2)–cultured whole mononuclear cells (WMC) and anti-Ig stimulated CD19+ B cells were resistant to the induction of apoptosis by rolipram while unstimulated CD19+ B cells, which had a high basal apoptotic rate, were more sensitive. Rolipram stimulated elevations in cAMP levels in all four of these cell populations, suggesting that they differed in sensitivity to cAMP-induced apoptosis. Consistent with this hypothesis, incubation with the cell permeable cAMP analog dibutyryl-cAMP induced apoptosis in CLL cells and unstimulated B cells but not in IL-2–cultured WMC or anti-Ig stimulated B cells. These data identify PDE4 as a family of enzymes whose inhibition induces apoptosis in CLL cells.

Noncoding RNAs play a pivotal role in the pathogenesis of chronic lymphocytic leukemia (CLL). We hypothesized that microRNAs (miRs) are involved in the transition from monoclonal B-cell lymphocytosis (MBL) to CLL and tested miR-15a/16-1 cluster, miR-21, and miR-155 expression in purified B cells of normal individuals, individuals with MBL, and patients with CLL. When we analyzed 224 samples from 2 independent training and validation cohorts, we found that miR-155 was overexpressed in B cells from individuals with MBL, and even more so in B cells from patients with CLL, when compared with B cells from normal individuals. Furthermore, we were able to identify miR-155 in circulating microvesicles from both individuals with MBL and patients with CLL. Next, to examine the prognostic role of miR-155, we measured its expression level in plasma samples collected before treatment initiation in 228 patients with CLL. We found significantly higher miR-155 expression levels in patients who failed to achieve a complete response compared with those who experienced complete response. Our findings support the use of cellular and plasma levels of miR-155 as biomarkers for the risk of progression in individuals with MBL, as well as to identify patients with CLL who may not respond well to therapy.