Sloan, Jeff A.

Abstract BACKGROUND Treatment options and prognosis are limited for patients with high grade glioma (pwHGG), underscoring the importance of patient and caregiver understanding to prioritize goals of care and quality of life (QOL). Although addressed by multiple providers, patients and caregivers may experience discordance in understanding the prognosis. This may be related to patient/caregiver perception, cognitive decline as a result of the tumor and/or treatment, or failure by the clinician to clearly articulate this information under emotional circumstances. AIMS: To evaluate the longitudinal perception of prognosis of patients compared to their caregivers and their providers during the adjuvant treatment of newly diagnosed HGG. METHODS After IRB approval, 16 pwHGG, their caregivers and their providers reported an overall survival estimate at each monthly visit during adjuvant treatment, as part of a larger survey. Options included “weeks,” “weeks to several months,” “several months to years,” “indefinite number of years”, or “I do not wish to answer.” RESULTS Seven of the sixteen patient/caregiver clusters have completed the appropriate duration of the study with the remaining completing in November. The perception of the patient differs from the caregiver at almost each visit. Regardless of the counseling provided by provider, the perception of both tends to change at each visit and can vary from dismal to overtly optimistic. There does not appear to be discrepancy between the neuro-oncology and palliative care provider’s perception of prognosis. CONCLUSION Newly diagnosed pwHGG and caregivers vary in their perception of prognosis, deviating not only from each other but also differing at each visit throughout the course of their illness. The providers’ perception appeared to remain consistent but often varied from that of the patient and caregiver. Providers need to be aware that prognostic understanding appears to fluctuate throughout the course of illness and cannot be clarified via a single discussion.

Abstract BACKGROUND Early involvement of palliative care (PC) in patients with metastatic cancer has been associated with improved quality of life (QOL). Patients with high grade glioma (pwHGG) and their caregivers have unique needs such that similar results are anticipated in this population but cannot be extrapolated. Recognizing that pwHGG often require a caregiver early in the course of disease, this patient population also experiences significant personal and caregiver distress that has been given limited attention and resources. AIM: To assess the feasibility of implementation of a novel patient reported outcomes (PRO) quality of life (QOL) tool administered by smart device in routine office visit (OV) and early integration of palliative care (PC) for pwHGG and their caregivers to improve QOL for both. DESIGN: Prospective, single-center cluster-randomized pilot conducted for 6 months during completion of adjuvant therapy for newly diagnosed high grade glioma. After informed consent was obtained, 15 pwHGG and their caregivers were randomized to: routine OV with basic QOL survey; OV with PROQOL; or PC consultation, in addition to OV with PROQOL. RESULTS Two elderly patients with declining performance status transitioned to hospice after initial visit, and one moved out of state prior to adjuvant visits. Thus far 5/15 patients/caregivers have successfully completed the pilot with the 6 remaining participants due to complete in November 2019. DISCUSSION The PROQOL appears to be easily integrated into OV without significant patient, caregiver, or provider burden. Providers confirmed utility in prioritizing symptoms and concerns. Thus far, it appears that patients (and caregivers) appeared to benefit from the PROQOL and PC support as evidenced by longitudinal improvement in QOL scores over the control group. CONCLUSIONS A unique PROQOL tool and early PC can be easily integrated into practice, and may improve the QOL of pwHGG and their caregivers.

Abstract INTRODUCTION The impact of treatment on both the quality and the quantity of life, i.e. the ‘net clinical benefit’, should be considered to facilitate shared decision making. Two methods that combine survival and health-related quality of life (HRQoL) data: Quality Adjusted Effect Sizes (QASES) and Joint Modelling (JM) were applied to gain insight in the net clinical benefit. METHODS The net clinical benefit in one RCT (EORTC 26951 comparing radiotherapy (RT) + PCV chemotherapy versus RT alone) was calculated as a proof of concept for other trials. With the QASES method, effect sizes for differences in survival and HRQoL between treatment arms were calculated. JM allows simultaneous modeling of a longitudinal outcome (HRQoL), and a time-to event outcome (survival). HRQoL scales/items that were selected for primary analysis in the main study were also selected for this analysis: fatigue, global health, social functioning, communication deficit, seizures, physical functioning, and nausea/vomiting. RESULTS 288/386 patients completed baseline HRQoL forms and were included in the analysis. Overall survival (OS) was significantly longer with combined treatment (42.3 vs. 30.6 months). The percentage of patients who experienced a clinically relevant deterioration (≥10 points) in nausea/vomiting, fatigue, social functioning and global health up to one year after treatment compared to baseline was larger in the RT+PCV arm. QASES corresponded to a reduction in the median OS difference from 9.7 months up till 5.5 months, given equal weights to OS and HRQoL. JM analyses resulted in a theoretical loss of treatment effect in OS of 2–6% when adjusting for HRQoL. CONCLUSION Both methods showed that adjusting for the impact of treatment on a relevant HRQoL parameter reduced the survival benefit in the experimental treatment arm compared to standard treatment arm. Applying these methods may facilitate communicating the impact of treatment to patients in clinical practice.

Abstract Background: Modern clinical practice places time restrictions on the amount of information and processing that can be done in a typical office visit. Meeting patient needs within the healthcare system is challenging, contributing to patient (pt) and clinician dissatisfaction and potential suboptimal outcomes. We developed an electronic point-of-care case management system for cancer patients. The system's goal is to obtain patient-reported quality of life (PROQOL) outcomes and provide clinicians with information regarding QOL issues to address. We tested this system in a prospective randomized study against usual care (UC). The primary objective was to determine if PROQOL system would improve mean QOL over time. Methods: Eligible pts were adults with multiple myeloma (MM) or light amyloidosis (AL), seen at Mayo Clinic. Pts were randomized 2:1 to PROQOL system or usual care. PROQOL system was offered prior to every visit. Pts select from various categories about their single biggest concern, and receive a printed list of actionable resources based on selected concern. Clinicians also receive the PROQOL results to review with pts. Providers and pts randomized to PROQOL completed a "was it worth it survey" (WIWI). An 8 item Linear Analogue Self-Assessment was used to assess QOL, the primary endpoint. Secondary endpoints included distribution of choices of most important concern and their relationship to demographic and clinical variables. The study was powered to detect a 0.5 standard deviation difference in QOL between groups. Results: There were 233 patients enrolled (171 MM, 62 AL) in this study between July 1, 2016 and April 17, 2018. Median age was 65 years (range 31-87), and 59% were male. Median time from diagnosis to study consent was 37 months (PROQOL 36.3 versus UC 39.6). Median follow up for all patients was 15 months (range: 0.7-22 months), and median follow up for PROQOL pts was 16 months and 14 months for UC pts (p=0.027). There were 25 pts that have died since enrollment and 208 alive. No statistical significant difference in QOL between PROQOL and UC (median QOL 7 vs 7, p=0.75). The most prevalent main concerns selected were Physical Health (37%) and Cancer and Diagnosis (27%), the pattern remained even when pts were given the option to pick a second major concern 26% and 20% respectively. No other concern was listed more than 8% at baseline. All category selections and percentages are shown in the Figure. The average time to complete the instrument was 6 minutes. Pts found the PROQOL system was worth their time (75%), they would choose it again (87%) and recommend it to others (82%). Eighty-two percent of clinicians did not think the PROQOL tool negatively impacted their practice and 75% believed they may see improvement in pt wellbeing. Discussion: The PROQOL system was well received by pts and clinicians but did not improve QOL relative to UC in this study. The PROQOL demonstrates that majority of patients strongly desire more information regarding ongoing therapy, clinical trials, prognosis and toxicity. Further investigation is needed to understand whether communication is limited by time or mechanism of information delivery, such as verbal or written, or whether it should be undertaken in a separate allied health care visit. Figure. Figure. Disclosures Gertz: spectrum: Consultancy, Honoraria; Abbvie: Consultancy; Research to Practice: Consultancy; annexon: Consultancy; Medscape: Consultancy; Physicians Education Resource: Consultancy; Amgen: Consultancy; janssen: Consultancy; Alnylam: Honoraria; Teva: Consultancy; Apellis: Consultancy; Ionis: Honoraria; celgene: Consultancy; Prothena: Honoraria. Kumar:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Lacy:Celgene: Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.

Abstract Abstract 630 Introduction: Erythropoiesis stimulating agents (ESAs) improve hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients (pts) with chemotherapy-associated anemia (CAA), but many pts with CAA do not respond to ESAs. Functional iron deficiency due to inflammation-related hepcidin production and pathological sequestration of bioavailable iron may be an important reason for lack of ESA response in iron-replete pts. The common clinical practice of co-administering oral iron with ESAs does not appear to alter the disordered iron processing in CAA. We conducted a prospective trial to evaluate whether parenteral iron might overcome functional iron deficiency and benefit iron-replete pts with CAA undergoing ESA treatment. Patients and Methods: Eligible pts were receiving chemotherapy for a non-myeloid neoplasm and had Hb level <11.0 g/dL, ferritin >20 ng/mL, transferrin saturation <60%, and ECOG performance score ≤2. All pts received darbepoetin alfa (DA) 500 mcg subcutaneously q3wks until Hb reached >11 g/dL, and thereafter DA 300 mcg q3wks; DA was held for Hb >13 g/dL until Hb fell to <12 g/dL, then restarted with 25% dose reduction. Pts were randomized 1:1:1 to receive either sodium ferric gluconate complex in sucrose (Ferrlecit) 187.5 mg intravenously q3wks (total dose 1,125 mg), oral ferrous sulfate 325 mg once daily, or oral placebo. Quality of life (QOL) was measured using the Symptom Distress Scale, Brief Fatigue Inventory, FACT-An, and LASA instruments. The primary endpoint was the proportion of patients achieving Hb ≥12.0 g/dL or ≥2.0 g/dL Hb increment from baseline by the end of the 16-week study. Secondary endpoints included transfusion requirements. changes in QOL, changes in iron parameters, and adverse events (AEs). Results: Planned enrollment was 582 pts, but the study met an early stopping rule due to an excess of serious AEs in the IV iron arm; 502 pts enrolled at 14 MCCRC sites between February 2006 and December 2008. The median age of the 490 evaluable pts was 64 years; 65% were female and 94% white; 6% had hematological neoplasms (lymphoma or multiple myeloma), 25% had severe anemia (Hb <9.5 g/dL), 48% received platinum-containing therapy, and 66% completed all 16 weeks of the study. Baseline characteristics were comparable between groups. With respect to the primary endpoint, 69.5% of IV iron-treated pts achieved a Hb response (median Hb increase from baseline to end of study, 2.7 g/dl), compared to 66.9% with oral iron (median increase, 2.4 g/dL) and 65.0% with placebo (median increase 2.3 g/dl) (p=0.73). There were no significant differences in the proportion of patients requiring RBC transfusion (12.8% for IV iron, 12.9% for oral iron, 13.5% for placebo; p=0.87) or QOL changes. A total of 17 pts (3%) died on study–8 in the IV iron arm, 6 oral iron, 3 placebo (p=0.22). Grade 3 or higher AEs occurred in 54% of IV iron pts compared to 43% for oral iron and 45% placebo (p=0.03). The end-of-study ferritin level was higher in the IV iron arm (median 501 ng/mL) compared to the oral iron (229 ng/mL) and placebo (193 ng/mL) arms (p=0.0022). The median total DA dose administered was similar between arms (p=0.71). Conclusions: Co-administration of DA with intravenous ferrous gluconate q3wks did not result in improvement in Hb levels, reduce transfusions, improve QOL endpoints, or allow lower doses of DA, compared with DA + oral iron or DA + placebo. IV iron increased AEs. The reason for discordant results with 5 previous smaller studies is unclear. Disclosure: The study was supported by a grant from Amgen (Thousand Oaks, CA) to the MCCRC. Disclosures: Off Label Use: Ferrlecit, chemotherapy-associated anemia.

Abstract Relatively little is known about the quality of life (QOL) status among long-term (5–20 year) lymphoma survivors. Using the Mayo Tumor Registry, we identified eligible patients who were 16 years or older at diagnosis, U.S. residents, first diagnosed with Hodgkin or non-Hodgkin lymphoma from 1984–1998, diagnosed and/or initially treated at Mayo Clinic Rochester, and survived for 5 to 20 years (N=2,485). In October of 2004, we mailed a 23-page survey to 95 randomly selected patients; 7 were found to be ineligible (deceased or too ill). Of the 88 remaining patients, we were able to find a correct address for 82, and 57 completed a survey for a 70% participation rate. QOL assessments included the Functional Assessment of Cancer Therapy - General (FACT-G), and a series of linear analogue self-assessment (LASA) single-item QOL measures. Results for the pilot sample were compared to normative data for each measure relating to general cancer patient populations. All scores were transformed onto a 0–100 point scale (higher score meaning higher functioning) for ease of comparison. Of the 54 patients with complete data for analysis, the mean age at survey was 60.8 years (6.3–19.9). The mean time since diagnosis was 12.0 years (6.3–19.9), and 52% had survived more than 11 years. The mean total score for the FACT-G was 89 compared to a norm of 74 for cancer patients. Higher scores were also seen in the lymphoma survivors in each of the four FACT-G subdomains (physical, social/family, emotional and functional well-being) compared to normative cancer patient populations. The global LASA QOL measure was also higher among lymphoma survivors (mean score of 82 compared to a norm of 77), and only 7% reported a global QOL score of 50 or lower, indicative of impaired QOL. Functioning among the lymphoma survivors was higher compared to general cancer patients on the mental, physical, emotional, social, pain, fatigue, financial, and legal LASA items, while functioning was similar to general cancer patients on the spiritual and support LASA items. However, scores suggestive of impaired QOL were reported by more than 10% of the patients for the social (17%), pain frequency (31%), fatigue (20%), and financial concerns (25%) items of the LASA. There were suggestive results of effect sizes indicating that smokers had lower FACT-G physical and emotional scores, and lower LASA mental and physical QOL scores, although none achieved statistical significance. In conclusion, this pilot sample of long-term lymphoma survivor patients reported having high QOL on most domains of the FACT-G and LASA relative to other cancer patient populations. There appears to be a subset of patients who experience impaired QOL and who may require further interventions, particularly in the QOL domains of social, pain, fatigue, and financial functioning. These results also suggest that awareness of smoking status may be important. Further larger studies are needed to confirm these preliminary data and to evaluate other aspects of QOL.

Abstract Patients during cancer treatment and cancer survivors frequently utilize complementary and alternative medicine (CAM) therapies. While the beliefs and knowledge regarding CAM of many cancer-specific patient groups have been well studied such as breast cancer patients and prostate cancer patients, no specific evaluation of lymphoma survivors and their beliefs and knowledge about CAM has been undertaken. Because CAM can yield both risks such as toxicity and displacement of efficacious therapy as well as potential benefits such as improvement in quality of life and mood, we surveyed lymphoma survivors in a pilot study to ascertain their current beliefs, knowledge, and utilization of CAM. Using the Mayo Tumor Registry, we identified eligible patients who were 16 years or older at diagnosis, U.S. residents, first diagnosed with Hodgkin or non-Hodgkin lymphoma from 1984–1998, diagnosed and/or initially treated at Mayo Clinic Rochester, and survived for 5 to 20 years (N=2,485). In October of 2004, we mailed a 23-page survey to 95 randomly selected patients; 7 were found to be ineligible (deceased or too ill). Of the 88 remaining patients, we were able to find a correct address for 82, and 57 completed a survey for a 70% participation rate. Complete data were available on 54 patients at the time of this analysis. The mean age at completion of the questionnaire was 60.8 years (26.1–86.7). The mean time since diagnosis was 12.0 years (6.3–19.9), and 52% survived more than 11 years. The histologies included 22 (39%) Hodgkin lymphoma, 21 (38%) diffuse large B-cell, 3 (5%) follicular, 1 (1%) high grade, 5 (9%) peripheral T-cell lymphoma, and 4 (7%) other. A majority of patients expressed no knowledge about the use of CAM cancer care, while only 4% of patients responded that CAM could both cure cancer and that it was perfectly safe. Ten to twenty percent of patients felt that CAM could assist other therapeutic interventions, relieve symptoms, assist the body to heal or increase quality of life. Fifteen percent of patients reported that CAM utilization increased the feeling of control, and 24% reported that CAM could have side effects. With respect to CAM utilization, overall 32% of patients had ever used CAM, but no patients reported that CAM usage was directed specifically towards their lymphoma. The most commonly used CAM modalities were chiropractic (39%), massage (21%), relaxation therapy (7%), meditation (5%) and acupuncture (5%). Overall usage of dietary supplements was relatively low, with green tea, garlic, flax seed, and echinacea being the only dietary supplements used by more than 10% of respondents. Five percent had used St. John’s Wort and 7% had used shark cartilage. In conclusion, lymphoma long-term survivors appear to use CAM at a rate similar to the general population, which does not follow the typical pattern seen in other cancer survivorship populations. The use of St. John’s Wort has potential risks if not identified prospectively. At the same time, lack of access to potentially beneficial modalities was also identified, and these observations suggest the opportunity for further study of targeted educational interventions regarding the use of CAM in this population.

Abstract Abstract 3008 Poster Board II-984 Introduction: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients (pts) with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (i.e., administration less than once weekly) is a common practice with DA, which is FDA approved for dosing once every 3 weeks (q3wks); a previous study of the North Central Cancer Treatment Group suggested that EA can also be given less often than the FDA-approved once weekly schedule (Steensma DP et al, J Clin Onc 2006; 24:1079). The present study compared 2 different q3wks extended-interval EA regimens with weekly fixed-dose EA and with q3wks DA in pts with CAA. Patients and Methods: Eligible pts were receiving chemotherapy for a non-myeloid malignancy and had Hb <10.5 g/dL, ferritin >20 ng/mL, weight >40 kg and <150 kg, and ECOG performance score £2. Pts were randomized 1:1:1:1 to receive EA 40,000 Units subcutaneously (SC) once weekly (40K arm), EA 80,000 Units SC q3wks (80K arm), EA 120,000 Units SC q3wks (120K arm), or DA 500 mcg SC q3wks (DA arm), for 15 weeks. EA and DA were held for Hb >12 g/dL and restarted at a lower dose when Hb fell to '11.5 g/dL. All pts received ferrous sulfate 325 mg orally once daily, if tolerated. Quality of life (QOL) was measured using the Symptom Distress Scale (SDS), Brief Fatigue Inventory (BFI), FACT-An, and Linear Analogue Self Assessment (LASA) tools. The primary endpoint was the proportion of pts achieving Hb≥11.5 g/dL or increment of Hb>2.0 g/dL from baseline. Secondary endpoints included RBC transfusion requirements, adverse events (AEs), and QOL. Results: 239 pts (236 evaluable) enrolled at 10 MCCRC sites between Feb. 2007 and Dec. 2008; 62% of pts completed all study interventions. The median age of enrolled pts was 66 years; 42.4% were men, 91.5% had solid tumors, 26.7% had severe anemia (Hb <9.5 g/dL), and 44.9% were receiving platinum-containing regimens. Baseline characteristics were balanced between study arms, with the exception of gender (39% female for 40K, 60% for 80K, 43% for 120K, 26% for DA). There were no significant differences between treatment arms in the proportion of pts achieving a Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; p>0.41 for all comparisons), but the median Hb increment from baseline was higher in the 40K and DA arms compared to the 2 extended dosing EA arms (40K-2.8 g/dL, 80K-2.0 g/dL, 120K-2.1 g/dL, DA-2.6 g/dL; p=0.005 for 40K vs 80K). Hb response was achieved more quickly in the weekly EA arm, but the difference was not significant (40K-32 days, 80K-50 days, 120K-49 days, DA-49 days; p>0.13). The proportion of patients transfused was similar between arms (40K-27.9%, 80K-33.3%, 120K-22.4%, DA-29.8%; p>0.49). There were no significant differences in QOL changes. Deaths were also similar between arms (40K-5 pts, 80K-7 pts, 120K-7 pts, DA-1 pt, p>0.10) and were primarily due to disease progression. AEs and serious AEs were comparable between study groups; grade 3/4 AEs were observed in 22% of pts in the 40K arm, 22% on 80K, 17% on 120K, and 13% on DA; p>0.56. The median total dose of EA used was highest in the 120K arm (40K-265,000 U; 80K-240,000 U; 120K-360,000 U; p=0.0009 for 40K vs 120K), while pts on the 40K arm were more likely to omit a dose due to a high Hb (40K-63.9% of pts omitted at least one dose; 80K-30.0%; 120K-34.5%; DA-43.6%, p<0.0001 for 40K vs 80K). Conclusion: Although there was no significant difference in the proportion of responding pts (the primary endpoint), Hb increments from baseline were moderately higher with the 2 FDA-approved regimens – weekly EA 40,000 Units, and q3wk DA 500 mcg – than with the extended dosing regimens. This study was supported by a grant from Centocor Ortho Biotech, Inc. to the MCCRC. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Inflammatory deregulation may be a major factor in cancer related symptoms (Dantzer Nature Rev Clin Oncol 2012). Improved symptoms in myelofibrosis (MF) patients treated with single arm ruxolitinib (JAK1/JAK2 inhibitor) studies has been correlated with normalization of selected cytokines increased pre-therapy (c-reactive protein, IL-1ra, MIP-1b, TNF-a, and IL-6; Verstovsek NEJM 2010). We sought to assess the impact of JAK1/JAK2 inhibitor therapy on cytokine levels and the relationship between cytokine levels and symptoms prior to and during JAK1/JAK2 inhibitor therapy in the phase III placebo controlled COMFORT-I trial (Verstovsek NEJM 2012). Methods Cytokine levels (89 cytokines measured at baseline and at weeks 4 and 24) and MF symptoms (assessed by MFSAF 2.0 – Mesa JCO 2013) were collected during the blinded phase of COMFORT-I. Patients were randomized to ruxolitinib vs. placebo. Plasma was used for the measurement of cytokines using Rules-Based Medicine, Inc. (Austin, TX) Human MAP panel. Associations between the MFSAF total symptom score (TSS) and log2-transformed cytokine data were investigated at baseline using Spearman correlations and linear regression. Mixed models were used to assess cytokine and TSS changes over time within each arm and overall. Logistic regression was used to assess the relationship between baseline cytokines and TSS response (>/=50% reduction from baseline) at week 24, and between week 4 cytokine changes and TSS response (>/=50% reduction from baseline) at week 24 within each arm and overall. Mixed and logistic regression models combining data across arms also included terms for visit, arm, and visit-by-arm interaction. All models also included age, gender, and body mass index (BMI). Given the large number of cytokines being investigated, p<0.001 was considered statistically significant. Cytokine values below the limit of detection were set at the lowest limit of detection and 25 cytokines were excluded from statistical analysis due to having more than 30% of data missing or below the limit of detection. Results Patients: 309 subjects were randomized in COMFORT-I with median age 68 (range 40-91), 46% female, 50% primary myelofibrosis, and 61% high risk. All 309 subjects had cytokines measured at one or more of the three visits included in this analysis, with 308 having cytokine values paired with a TSS score at the same visit. Cytokines at Baseline: At baseline, the highest Spearman correlations with symptomatic burden (as assessed by the TSS) were observed for APOA1 (rho=-.21) and FERRITIN (rho=-.20), followed by INTLK5, MIP1A, MMP3, INTLK2, MGB, INTLK1A, and INTLK7 with correlations between -.15 and -.17 (all p<0.01). After adjusting for age, sex, and BMI, VCAM1 and APOA1 were significantly associated with TSS at baseline. Cytokine and Symptom changes during trial: Changing levels of 5 cytokines were significantly associated with change of TSS over time beyond the change due to visit, arm, visit-by-arm interaction, age, sex and BMI including VCAM1, LEPTIN, TIMP1, B2MICG, and TNFRII. Within the placebo arm, only 5 cytokines significantly changed over time compared to 46 cytokines in the ruxolitinib arm (visit-by-arm interaction was significant for 43 in the overall models). VCAM1, B2MICG, and TNFRII were among the 5 cytokines which changed in the placebo arm, and VCAM1, LEPTIN, TIMP1, B2MICG, and TNFRII were among the 46 cytokines which changed in the ruxolitinib arm. No baseline cytokines and no changes in cytokines at week 4 univariately predicted week 24 TSS response within either arm at the p<0.001 level. Conclusions In the first serial assessment of MF symptoms and plasma cytokine levels in the conduct of a placebo controlled trial we found 5 cytokines in which improved levels correlated with decreased MF symptom burden in ruxolitinib treated patients. Development of a multivariate model for predicting symptom response, correlations with splenic response and impact on survival benefit of therapy is ongoing. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2059 Introduction: Two randomized trials have demonstrated a benefit in progression free survival (PFS) of 18–20 mofor maintenance treatment with lenalidomide after auto-PBSCT for multiple myeloma (MM). Although results on survival benefit are conflicting and quality of life (QOL) data is lacking, some have begun to recommend maintenance. No study has evaluated patient perceptions of maintenance. We conducted a systematic survey of MM patients (pts) regarding what constitutes a meaningful benefit that would make burdens of maintenance (toxicity and cost) acceptable. Methods: We mailed a brief self-administered survey in 3 waves to 1159 consecutive living pts evaluated at Mayo Clinic. The survey provided background on the standard of care for MM in transplant eligible pts and data on maintenance. Pts were asked to estimate the magnitude of OS benefit that would be acceptable for varying degrees of toxicity and cost. Results: Of the 1159 surveys sent, 886 pts (83.2%) responded, including 150 notifying us of a decision not to participate. 736 pts returned a completed survey (66% raw response rate). (56%) male, 407 (55%) had undergone auto-PBSCT, 467 (63%) had discussed maintenance with a physician, and 9 (1%) pts had received no treatment. 10% of pts had MM for 3–12 mo, 14% for 1–2 yr, 13% for 2–3 yr, 20% for 3–5 yr, 44% for 5 yr or more. Pt age: 4% 18–49 yr, 24% 50–59 yr, 40% 60–69 yr, 27% 70–79 yr, and 6% >80 yrs. The most worrisome potential toxicity was identified as peripheral neuropathy by 27% of pts, cytopenias by 24%, LE DVT 20%, fatigue 15%, nausea 8%, diarrhea/constipation 7%. In response to a question about whether they would choose maintenance if there was a PFS benefit but no improvement in OS, 92% would opt for maintenance if it were known to cause mild toxicity, while 77% would opt for maintenance despite moderate toxicity. Subsequent questions included cost and toxicity considerations and required pts to identify minimum acceptable duration of OS benefit to estimate more precisely a meaningful clinical benefit. If treatment was free, had no toxicity, and the OS benefit was 1 yr or less, 49% would choose maintenance (see Figure). In the same scenario, if toxicities were mild, the proportion of pts who choose maintenance was similar (46%). If pts experienced moderate toxicity, 42% choose maintenance. With rising financial burden (out-of-pocket) and toxicity, the proportion of pts who choose maintenance declined (see Table). For example, if the cost was $25/mo, mild toxicity experienced, and the OS benefit was one year or less, 46% would choose maintenance, while 39% of pts would choose maintenance if it cost $250/month and there was moderate toxicity. If maintenance cost $10,000/mo and was associated with mild or moderate toxicity, 18% and 17% of pts would choose treatment, respectively. Conclusions: For the first time, we have described the broad range of patient perspectives regarding trade-offs in the treatment of MM with maintenance therapy. We found that willingness to be treated with maintenance declined when actual benefits were provided in concrete numeric terms compared with a general statement of PFS benefit. The discrepancy between the 92% of pts choosing to undergo maintenance if free and mild toxicity when there is a PFS benefit but no OS benefit, compared to 49% of pts choosing maintenance if free, mild toxicity, and associated with an OS benefit of 1 yror less; suggests pts have difficulty understanding the concept of PFS. We also found that the magnitude of benefit required to consider maintenance was affected by cost and toxicity. In our experience, pts typically incur a cost of approximately $25/mo and experience mild toxicity. In this study, nearly half (46%) of such pts would opt for maintenance if the OS benefit was 1 year or less while only 33% of pts would opt for maintenance if the OS benefit was 6 months or less. Our data implies that good care in MM requires detailed conversations about each and every patient's priorities and expectations prior to making recommendations for or against such treatments. Disclosures: No relevant conflicts of interest to declare.