Carevive Systems Research Articles

Impact of a Brief Touchscreen Based Modified Geriatric Assessment on the Care of Older Adults with Multiple Myeloma

Background: Most adults (60%) diagnosed with Multiple Myeloma (MM) are > 65 years old (YO) and thus are at higher risk for toxicities of cancer treatment. Geriatric assessment (GA) can identify patients at risk for toxicity and morbidity more effectively than age or performance status, but is not easily integrated into a busy clinical setting. A technology assisted, modified GA (mGA) that includes the Palumbo frailty score can be used to summarize and report relevant clinical and self-reported symptom data to inform treatment decision making.Methods: A prospective, single arm multisite study is underway with MM patients >65 YO to test feasibility, usability, and acceptability of a technology based mGA in a busy clinic. Patients needing a new treatment complete a tablet based survey that includes 28 items comprising the Charlson Comorbidity Index (CCI), Katz Activity of Daily Living (ADL) Score and Lawton Instrumental ADL (IADL) Score prior to meeting with the provider. Additional clinical information such as Creatinine Clearance (CrCl) is added by staff. The composite frailty index (FI) and items influencing the score are provided on a physician facing dashboard at the patient/provider visit. The provider reviews the mGA results with the patient and treatment is selected.Results: To date, 118 of 210 patients have enrolled. Most participants are white (72%, n=86); mean age is 72 (range 65-85). Patients are satisfied with the computer program overall (84% indicated they are satisfied or very satisfied with the overall program), satisfied with the ease of use (91% were satisfied or very satisfied), and feel others can use the program easily (90% agreed or strongly agree others would learn to use the program quickly). Patients complete the survey in an average of 7.71 minutes (range 2-17) and providers report an average of 3.2 minutes (range 1-10) to review the mGA results. Patients were fit (38%, n=45), intermediate fit (31%, n=37) or frail (31%, n=36), and the fit/frailty status informed treatment decisions. Providers selected treatments that were more aggressive (increased dose or dose intensity) for the fit patients while frail patients received milder treatments evidenced by a reduced number of agents, regimens with less toxicity, or a different route of administration (χ2 =20.02, p<.0001). There was also a significant correlation of patients considered to be transplant eligible with fit status and patients considered not transplant eligible with frail status (p=.004). There is a trend toward frail patients having more dose modifications during the 3 months follow up period (p=.09). The mGA information with greatest impact on provider treatment decisions was: fit/frailty status or the rationale for the summary score (67%, n=100), creatinine clearance (17%, n=25), peripheral neuropathy (6%, n=9) and falls (3%, n=4). Outcomes on the first 18 patients at three months post treatment decision visit show 33% had grade 3 or higher hematologic toxicities, 66% had dose modifications over the three-month study period, and 33% had therapy discontinued earlier than planned.Conclusion: The limited additional time required by patients to complete the survey and-the provider to review the mGA results together with the high rate of patient satisfaction shows a mGA can be easily incorporated into clinical workflow. Real time scoring of assessment items into a composite score indicating fit/frailty status influenced treatment decisions at the point of care to allow aggressive treatment of fit patients and modifications to decrease toxicity in frail patients. Final study results will report patient outcomes at three months post intervention visit correlated with fit/frailty status. DisclosuresMohile:Seattle Genetics: Consultancy. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy. Wujcik:Carevive Systems Inc: Employment. Davis:Carevive Systems Inc: Employment. Digiovanni:Carevive Systems Inc: Employment. Stricker:Carevive Systems Inc: Employment, Equity Ownership.

Statin Use Is Associated with Decreased Mortality in Multiple Myeloma— a SEER Medicare Study

IntroductionStatins are a groups of drugs used in the treatment of hyperlidemia and in primary and secondary prevention of cardiovascular disease. Recently, there has been increasing interest in statins for their ability to improve survival and reduce risk of cancer due to their pleiotropic effects. Observational studies have reported survival benefit among patients with several cancers including pancreatic cancer, ovarian cancer and colorectal cancer. It has also been shown to reduce incidence risk in hematologic malignancies including lymphoid neoplasms. Recently, Sanfillipo et al (J Clin Oncol 2016 34:4008-4014) reported that statin use among patients with Multiple Myeloma (MM) was associated with decreased mortality in a Veteran Affairs (VA) database. We attempted to replicate these findings among older patients with MM using data from SEER-Medicare database.MethodsAll cases of MM diagnosed 2008-2013 in the SEER-Medicare claims were extracted along with their associated Medicare claims data from 2007-2014. Incomplete cases including: those diagnosed prior to age 65, death certificate or autopsy cases, and those not enrolled in Medicare Part A (inpatient), B (outpatient), and D (prescription) were excluded. Cases of suspected smoldering MM, those without MM defining “CRAB” symptoms and not treated within 6 months following diagnosis, were excluded using a pre-established algorithm (Fakhri, et al,Blood 2016 128:2348). Statin users, defined as having 2 or more prescriptions for statins within 1 year before and after diagnosis of MM, were identified by Part D claims. ICD-9 codes were used to identify patients with chronic kidney disease (CKD). Charlson comorbidity index (CCI) was calculated using a previously established algorithm. Receipt of novel MM agents as first-line therapy and stem cell transplant and bisphosphonate utilization within 1 year following diagnosis were defined as the presence or absence of the corresponding ICD-9 and HCPCS codes. Baseline characteristics were compared between statin users and non-users by Chi-square test and Student's T-test as appropriate. Multivariate analysis was performed by Cox proportional hazard modeling method. Statin exposure was also assessed as a time-dependent covariate to account for immortal time bias. All statistical analysis was performed using SAS software 9.4 (Cary, NC, USA)Results5935 patients were included in the study of which 1779 were statin users. Descriptive data is shown in table 1. Statin users tended to be slightly older, had a higher rate of CKD and higher mean CCI, but were slightly more likely to undergo ASCT (Autologous stem cell transplant). In the survival analysis, statin use (time-dependent) was associated with decreased mortality with an adjusted hazard ratio of (aHR- 0.91, 0.85-0.98, p=0.008). Use of novel agents, bisphosphonates, and stem cell transplant were all associated with decreased mortality; increasing age and CCI were associated with increased mortality. The full multivariate results are shown in table 2.ConclusionsStatins as a class of drugs exert their effect on mevalonate pathway by inhibiting HMG-CoA reductase for their cholesterol lowering effect and this disruption of mevalonate pathway has also been shown to induce apoptosis in MM cells. In vitro studies of MM cells have also shown to induce cell death and decrease proliferation when exposed to statins. This susceptibility of MM cells to statins in laboratory experiments has been further supported by findings in retrospective studies with Epstein et al (Int. J. Cancer 2017 141: 480-487) reporting reduced incidence of MM with statin use and Sanfillipo et al showing decreased mortality with statin use among patients with MM.In the present study we found that statin use decreased mortality by 9%. Our results are similar to the findings reported by Sanfillipo et al and further support a potential benefit of statin use among patients with MM. These results should be evaluated further in prospective clinical trials. [Display omitted] DisclosuresVij:Celgene: Honoraria; Konypharma: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Meyers-Squibb: Honoraria; Jazz: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Research Funding. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy.

Overexpression of EZH2 in Multiple Myeloma Is Associated with Poor Prognosis Regardless of Treatment with Novel Agents or High-Dose Chemotherapy

Background: EZH2 overexpression has been linked to the development and progression of a variety of cancers. Pawlyn et al (Blood Cancer J, 2017) recently reported that EZH2 overexpression among patients with multiple myeloma (MM) was associated poor prognosis. Their analysis included patients on varying treatment regimens over a number of years and, therefore, they were unable to determine if proteasome inhibitors (PIs), immunomodulatory drugs (IMIDs), or high-dose chemotherapy and transplantation (HDCT) can overcome the negative effect of EZH2 overexpression, as they have been shown to do for some other high-risk genetic profiles.Objectives: To independently confirm EZH2 overexpression is associated with poor outcomes and determine if PI, IMIDs, or HDCT can overcome this poor risk.Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis 10 from the CoMMpass study. The CoMMpass study enrolled 1000 newly diagnosed MM patients who are being tracked longitudinally for 5 years. CoMMpass collects sequential tissue samples as well as relevant clinical data. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving a PI and/or and IMID for initial MM treatment; and no prior malignancies in the past 5 years. RNA sequencing was performed on CD138-enriched bone marrow cells at MM diagnosis. EZH2 overexpression was defined as > 1 SD above mean expression. High-risk cytogenetics, defined as amp1q, del17p, t(4;14), t(14;16), t(14;20), were identified using custom SeqFISH software on long-insert whole genome sequencing data. All sequencing was performed by the Translational Genomics Research Institute (TGEN).Results: 646 patients in the dataset had EZH2 expression data and were included in the analysis. The median age was 63 at MM diagnosis, 58% were male and 76% were white. 33% were ISS stage I, 37% ISS stage II, and 30% ISS stage III. Cytogenetics was not available for 17% of cases. Of those with cytogenetics available, 53% had high-risk disease; 38% amp1q, 12% del17p, 12% t(4;14), 4% t(14;16), and 1% (14;20).15% of patients (n = 97) were classified as EZH2 overexpressors. Patients with ISS stage III disease were more likely to have EZH2 overexpression (26%) than stage II (13%) and stage I (9%) (p < 0.0001). EZH2 overexpression was also more common among patients with high-risk cytogenetics than those without (19% compared to 9%, p = 0.0022). Of patients with high-risk cytogenetics available, overexpression was most common among patients with del17p (24%) and least common among patients with t(4;14) (11%). EZH2 expression was not associated with age, race, or gender.629 patients had first-line treatment data available, of which 93% received a PI, 72% an IMID, 70% both. 45% of patients underwent HDCT during first-line treatment. In the multivariate analysis, EZH2 expression was consistently associated with poor prognosis regardless of regimen, with an increase in hazard ratio for progression or mortality ranging from 106%-173%. The results of the multivariate analysis are summarized in Table 1.Conclusions: We found that EZH2 expression was consistently associated with poor prognosis across all treatment regimens. It is important to note that we were unable to control for HRD by cytogenetics due to the high rate of missing data. EZH2 expression has previously been shown to predict response independent of HRD and, therefore, its omission should not alter the findings. Patients with myeloma overexpressing EZH2 are at increased risk of progression and death regardless of therapeutic regimen. Early-stage clinical trials of EZH2 inhibitors are currently ongoing in solid tumors and lymphomas and their testing should be expanded to MM. [Display omitted] DisclosuresWildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy. Vij:Amgen: Honoraria, Research Funding; Celgene: Honoraria; Abbvie: Honoraria; Bristol-Meyers-Squibb: Honoraria; Takeda: Honoraria, Research Funding; Jazz: Honoraria; Konypharma: Honoraria; Janssen: Honoraria.

A Cost-Benefit Analysis of Bortezomib, Lenalidomide, and Bortezomib/Lenalidomide Combination Therapy for Newly Diagnosed Multiple Myeloma

Background: Advances in the treatment of multiple myeloma (MM) have markedly improved its prognosis. Novel agents such as bortezomib (BTZ) and lenalidomide (LEN) have largely replaced traditional chemotherapy due to their greater efficacy and better tolerability. However, the optimal sequencing of these treatments is still unclear as head-to-head trials are lacking. In SWOG S0777, combination BTZ, LEN, and dexamethasone (DEX) for first-line therapy induced higher remission rates and improved overall survival (OS) by 11 months (75 months compared to 64 months, p = 0.025) over LEN and DEX alone (Durie, et al, Lancet, 2017). However, combination treatment was more toxic with over twice as many patients discontinuing treatment (23% compared to 10%). The study did not analyze the cost implications of combination therapy, which is likely substantial as the cost of either BTZ or LEN alone is. The regimen's impact on healthcare costs and quality-of-life (QOL) should be considered when evaluating its utility.Objective: In this study, we aim to compare the costs and benefits of BTZ, LEN, and BTZ/LEN combination therapy for first-line MM treatment using real-world cost data from the SEER-Medicare database.Methods: All patients diagnosed with MM from 2007-2013 were identified in the SEER-Medicare database. Patients were considered eligible for the analysis if they were over 65 years of age at diagnosis, had Medicare Part A and B for 12 months prior to and Part D at the time of diagnosis, had an overall survival of at least 12 months, and received induction therapy with BTZ, LEN, or BTZ/LEN combination therapy. Patients who received any additional anti-MM therapy or underwent stem cell collection or transplantation within 6 months of MM diagnosis were excluded.All direct medical costs, including inpatient, outpatient, and prescriptions, were captured for the first 84 days of treatment, which corresponds to 3 4-week cycles of LEN or 4 3-week cycles of BTZ or BTZ/LEN. Costs included both those paid by Medicare and patient copays, coinsurance, and deductibles and were adjusted for inflation to 2014 dollars using the medical services section of the Consumer Price Index. Number of visits and length of inpatient hospital stays were also compared. Bivariate analysis was performed using Chi-square or ANOVA; multivariate analysis using linear regression.Results: 1162 patients were included in the final analysis, 542 in the BTZ cohort, 446 in the LEN cohort, and 174 in the BTZ/LEN cohort. The cohorts were similar in gender and racial composition; however, the BTZ/LEN cohort was younger with a median age of 72 years compared to 76 years for BTZ and LEN (p < 0.0001) and was less likely to have indicators of poor performance status (10% compared to 19% and 18%, respectively, p = 0.0348). The mean comorbidity index of the BTZ cohort was higher than the LEN and BTZ/LEN cohorts (1.9 compared to 1.3, p < 0.0001).The average drug cost for BTZ, LEN, and BTZ/LEN therapy was $17,439, $26,976, and $42,294 (p < 0.0001), respectively, and the total cost of care was $35,964, $39,295, and $59,127 (p < 0.0001). Controlling for variables such as age, comorbidities, and performance status, LEN was associated with $4,051 greater total cost of care (p = 0.0003) and BTZ/LEN with $23,213 greater total cost of care (p < 0.0001) compared to BTZ. The LEN cohort had an average of 14 days of interaction with the medical system compared to 23 days for each of the BTZ containing cohorts (p < 0.0001); the average number of days spent in inpatient settings was 5 in each cohort (p = 0.7602). OS in the BTZ and LEN cohorts was similar but BTZ/LEN was associated with a 36% decrease in hazard ratio (aHR 0.64, 95% CI 0.44-0.94) for mortality on multivariate analysis.Conclusions: First-line BTZ/LEN combination therapy is associated with superior OS but with increased drug costs. LEN and BTZ as single-agents had similar survival outcomes, and while LEN had higher drug costs, it is an oral formulation and had lower non-drug costs and reduced frequency of visits which improve its cost-utility. Newer agents such as carfilzomib, ixazomib, and daratumumab are increasingly being used for first-line therapy. We were unable to estimate the costs of such therapies because data is currently lacking. However, as drug costs are the largest driver of total cost of care, these newer agents will likely further increase the economic burden of MM treatment. [Display omitted] DisclosuresWildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy. Vij:Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy; Takeda, Onyx: Research Funding.

Cognitive Function in Older Adults with Hematological Malignancies

Background: Mild cognitive impairment is common with increasing age and can contribute to an increased risk of cognitive deficits that impair function and independence. Comprehensive geriatric assessment (CGA) predict treatment toxicity and tolerance in hematological malignancies. We utilized CGA and neuropsychological testing to describe vulnerabilities in a group of older adults awaiting autologous and allogeneic hematopoietic cell transplant (HCT).Methods: From August 2016 to June 2017, 30 consecutive patients ≥ 60 years with hematological malignancies who were considered for HCT completed CGA and neuropsychological assessment at the University of Nebraska Medical Center. Measures of cognitive functioning included a standardized battery of neuropsychological tests [Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery-CERAD-NP)] and Montreal Cognitive Test (MOCA). Patients completed Geriatric Depression Scale-15 (GDS-15), and carepartners completed a Collateral Source version of the GDS.Results: Patients had a median age of 69 years (range 61-78). MOCA and CERAD-NP were completed in 29 and 26 patients, respectively. Twenty patients met criteria for cognitive impairment and 6 patients met criteria for moderate-severe impairment (Table 1). Patients primarily displayed impairment in language, verbal and non-verbal memory, and >20% showed moderate-severe impairment in attention, executive functioning and visuospatial/visuoconstruction. Patients report a median of 3 (range of 0-8) symptoms on the GDS-15. 15% met criteria for depression, whereas 30% met criteria for depression based on reports from carepartners. Over 45% of patients have both impaired physical functioning on the Short Physical Performance Battery (SPPB <8) and cognitive impairment. One fourth of the patients have both cognitive impairment and one or more impairments in instrumental activities of daily living (IADL). In a subset of patients with HCT-CI score of 0-2, 34.5% met criteria for cognitive impairment, 25% had SPPB <8 and 31% had 1 or more impairments in IADL.Conclusions: Older patients with hematological malignancies, including those with HCT-CI score of 0-2 have a high prevalence of cognitive and functional impairment. Impaired memory and executive functioning have implications for their ability to adhere to complex medication regimens after HCT. Carepartners report more depressive symptoms suggesting that patients may be minimizing depressive symptoms. One fourth of patients are at high risk for further cognitive decline and disability due to preexisting cognitive impairment and impairment in IADLs. Prospective longitudinal studies are needed to better understand the trajectory and profile of cognitive changes in older HCT survivors and the impact of these cognitive changes on life activities and quality of life. [Display omitted] DisclosuresWildes:Janssen: Consultancy; Carevive Systems Inc: Consultancy.

Measuring Cardiopulmonary Complications of Carfilzomib Treatment and Associated Risk Factors Using the SEER-Medicare Database

Background. Next-generation proteasome inhibitor carfilzomib (CFZ) increases frequency and depth of responses, and improves survival in heavily pretreated patients with multiple myeloma (MM). In the clinical trials that led to the approval of CFZ, its use was associated with cardiac and pulmonary adverse events (CAEs and PAEs). However, the actual frequency of these events in the overall population is unknown because strict eligibility criteria in the clinical trials result in enrolling healthier patients. Moreover, the risk factors for developing these adverse events (AEs) remain to be established. Our objective was to estimate the incidence of CAEs and PAEs through administrative claims in the SEER-Medicare linked database. In addition, we aimed to identify the risk factors associated with developing these AEs.Methods. We extracted all plasma cell myeloma cases (ICD-O-3 histology codes 9731, 9732, and 9734) in the SEER-Medicare linked database from 2000-2013 and corresponding claims through 2014. We then used the Healthcare Common Procedure Coding System (HCPCS) codes for CFZ (C9295 and J9047) to identify patients who have undergone treatment with CFZ at any time point during their disease course. Patients receiving additional anti-MM therapy along with CFZ, except for corticosteroids, were excluded. Breaks in CFZ of more than 60 days were considered separate regimens and only data from first CFZ regimen was included in the analysis. Subsequently, we used the International Classification of Disease, ninth revision (ICD-9) to identify all the codes for CAEs and PAEs associated with CFZ usage that have previously been reported in the peer-reviewed literature. AEs were collected from first CFZ dose through 28 days following last dose or the start of additional anti-MM agents. AEs that were present within 90 days prior to CFZ were considered comorbidities and not included as toxicity. The frequency of CAEs and PAEs were reported using descriptive statistics. Multivariate Cox regression was performed to determine the variables that were independently associated with development of CAEs of interest (hypertension [HTN], ischemic heart disease, or congestive heart failure [CHF]), PAEs of interest (deep venous thrombosis [DVT], pulmonary embolism [PE], or pulmonary HTN), and respiratory infections (cough, upper respiratory infection, or pneumonia). All statistical analyses were performed using SAS Enterprise Guide 5.1. A p value of < 0.05 was considered statistically significant.Results. Six hundred and thirty-five patients were included in the final analysis. The median age was 72 (range 36-94). Fifty-five percent of the patients were male, 79% Caucasian, 17% African-American, and 4% belonged to other races. The median duration of CFZ treatment was 58 days (range 1-716), and the median duration from MM diagnosis to CFZ treatment was 54 months (range 3-170).In terms of CAEs, 22% of the patients developed new HTN; 15% and 13% developed peripheral edema and systolic/diastolic heart failure, respectively. New chest pain and ischemic heart disease affected 10% and 6% of the patients, respectively. The incidence of new cardiac dysrhythmias was 7%. In terms of PAEs, 25% of patients developed dyspnea and 15% developed a cough. Pneumonia and respiratory tract infections were each registered in 14% of patients. Venous thromboembolic events were documented in 6% of patients and 1% of the patients were afflicted with pulmonary HTN. The frequency of toxicities is reported in Table 1.With regard to the risk factors associated with developing toxicities, only COPD was found to be independently associated with developing CAEs of interest. Patients with pre-existing COPD had a 37% increase in hazard for developing HTN, ischemic heart disease, or CHF (aHR 1.37, 95% CI 1.01-1.87). The multivariate analysis is summarized in Table 2.Conclusions. With the expanding role of CFZ in the treatment of newly diagnosed and relapsed/refractory patients with MM, it is essential to identify the incidence of adverse events associated with its use in real-life practice settings. It is also critical to recognize any risk factors that predispose patients to developing these AEs to mitigate toxicity.To the best of our knowledge, this is the first and the largest SEER-Medicare linked study estimating the incidence of cardiopulmonary AEs and associated risk factors in patients with MM who received CFZ. [Display omitted] DisclosuresVij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy.

A new measure of function in older adults with cancer

A new measure of function in older adults with cancer

Cost-Effectiveness of Once-Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice-Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma

Introduction: The phase III BOSTON trial reported that once-weekly therapy with selinexor, bortezomib, and dexamethasone (SVd) significantly prolonged progression-free survival for patients with relapsed or refractory (R/R) multiple myeloma compared to twice-weekly treatment with bortezomib and dexamethasone alone (Vd). Although once-weekly SVd reduces the risk of disease progression as well as the cumulative exposure of patients to bortezomib and dexamethasone, selinexor is a costly drug-priced at nearly $22,000 per month-and is associated with significant toxicity. As a result, it is unclear whether SVd provides sufficient value in this clinical setting. In this study, we assess the cost-effectiveness of once-weekly SVd versus twice-weekly Vd in patients with R/R multiple myeloma. Methods: Our cost-effectiveness analysis was based on a Markov model. Simulated patients mirrored the cohort studied in the BOSTON trial; the median age of the population was 66 years, 57% were male and all had received 1-3 prior lines of therapy. Patients entered the model with R/R myeloma and received treatment with SVd or Vd; upon disease progression, all patients subsequently received identical lines of post-progression therapy. Our base-case model (Figure 1) followed SVd/Vd progression sequentially with daratumumab, carfilzomib, and dexamethasone (DKd), pomalidomide and dexamethasone (Pd), and best supportive care. We derived transition probabilities from large randomized trials using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. As data evaluating the quality of life with SVd vs Vd is not yet available, we assumed identical utility values for both treatment regimens. We calculated the incremental cost effectiveness ratio (ICER) from a US payer perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty in our model. Results: In our base-case model, SVd was associated with an improvement of 0.37 QALYs compared to Vd alone (3.43 vs 3.06 QALYs, respectively). However, the incremental lifetime cost of SVd was $177,126 ($1,013,851 vs $836,725, respectively), leading to an ICER of $479,572/QALY. The monthly cost of selinexor would need to be decreased by approximately 51%, from $21,424 to $10,415, in order for SVd to be cost-effective compared to Vd alone in R/R patients. Our model was most sensitive to the hazard ratio of SVd relative to Vd; decreasing the HR from 0.70 to 0.53 decreased the ICER to $285,251/QALY, while increasing the HR to 0.93 increased the ICER to $1,738,546/QALY. Of note, all ICERs during one-way sensitivity analysis and &amp;gt;99% of ICERs during probabilistic sensitivity analysis remained above the willingness-to-pay threshold of $150,000 QALY. We also incorporated two scenario analyses; in the first, patients in the Vd arm received therapy with selinexor and dexamethasone (Sd) after progression from Pd, before receiving best supportive care. In this scenario, SVd was associated with an incremental cost of $112,445 ($1,013,851 vs $901,406), an incremental effectiveness of 0.24 QALYs (3.43 vs 3.19 QALYs), and an ICER of $464,557/QALY. In the second scenario analysis, we assumed that patients had received DKd prior to SVd/Vd; as a result, patients that progressed on SVd or Vd subsequently received Pd followed by best supportive care. Here, SVd was associated with an incremental cost of $222,864 ($418,526 vs $195,662), an incremental effectiveness of 0.49 QALYs (1.90 vs 1.41 QALYs), and an ICER of $456,080/QALY. Conclusions: Use of once-weekly SVd for patients with relapsed or refractory multiple myeloma is unlikely to be cost-effective under current pricing, compared to twice-weekly Vd. The price of selinexor would need to be decreased substantially in order to reduce the ICER of SVd to widely acceptable values. Disclosures Huntington: DTRM: Research Funding; Pharmacyclics: Honoraria; TG Therapeutics: Research Funding; Genentech: Consultancy; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; AbbVie: Consultancy; Novartis: Consultancy. Giri:Carevive Systems: Research Funding; Carevive Systems: Honoraria; Pack Health: Research Funding.

Role of Neutrophil Lymphocyte Ratio [NLR] As a Biomarker of Frailty and Predictor of Survival Among Older Adults with Multiple Myeloma (MM)

Introduction: NLR combines a marker of inflammation (neutrophilia) and immune senescence (lymphopenia) to reflect aging related alterations in the immune systems. Prior studies have shown that NLR can serve as a marker of frailty and predict survival among older adults with solid tumors and lymphomas, its role among older adults with MM remains unclear. Methods: We used the Flatiron Health electronic health record-derived de-identified database to source older adults (age ≥60y) with incident MM diagnosed between 1/1/2011 and 2/1/2020. We limited our study cohort with known first line therapy and absolute neutrophil and lymphocyte count (cells//µL) up to 90 days before the start of treatment. We constructed a modified frailty index (Facon et al Leukemia 2020) at MM diagnosis combining age, comorbidity and ECOG performance status, captured within 90 days from the start of first line therapy categorizing patients into frail vs nonfrail. We examined the association between NLR (stratified into quartiles, Q1-Q4) and frailty using logistic regression model adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for age, sex, race/ethnicity, international staging system (ISS) stage, high-risk cytogenetics (HRCA; del17p, t4;14 or t14;16), and first-line therapy. Results: Of 2792 eligible patients, the median age at MM diagnosis was 73y (IQR: 67-78y), with 53% males and 61% non-Hispanic whites. Of these, 56% had IgG isotype, 22% ISS stage-III and 13% had HRCA. The median NLR was 2.29 (IQR: 1.5 to 3.59). Of the 1,743 evaluable for frailty, 1042 patients (59.8%) were frail. Overall, 45% received proteasome inhibitor (PI) + Immunomodulatory agent (Imid) based first line therapy and 19% received autologous stem cell transplantation. Patients in the highest NLR quartile were at a 2.1-fold higher odds of being frail (95% CI 1.52-2.86; p &amp;lt;0.001) when compared with those in the lowest NLR quartile (after adjusting for age, sex and race/ethnicity). NLR was poorly correlated with age (Pearson's r= 0.02). Patients in the highest NLR quartile had an inferior overall survival vs those in the lowest quartile (median OS/3y-OS in Q4 3.3y/53% vs 4.7y/69% in Q1; log-rank p &amp;lt;0.01). Similar results were seen when limiting to patients receiving first line PI &amp; Imid triplet and PI or Imid based doublet regimens (Fig 1). In a multivariable analysis, patients in the highest NLR quartile had a 1.5 times increased hazards of death (95% CI 1.28-1.85, p &amp;lt;0.001) when compared with those in the lowest NLR quartile, after adjusting for potential confounders (Table 1). Conclusion: NLR is an easily available laboratory biomarker associated with frailty as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM and guide appropriate treatment selection and targeted interventions to prevent excess toxicities and improve outcomes. Table 1 Disclosures Giri: Pack Health: Research Funding; Carevive Systems: Research Funding; Carevive Systems: Honoraria. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Costa:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy.

Multiple Myeloma (MM) in the Very Old: Disease Characteristics, Treatment Patterns and Outcomes in the Real World

Introduction: Older adults with MM continue to remain under-represented in clinical trials, leading to paucity of information regarding the clinical characteristics and treatment outcomes, particularly among those 80y or older at the time of diagnosis. The International Myeloma Working Group (IMWG) classifies any patient &amp;gt;80y as frail, irrespective of their fitness status. The value of geriatric assessment and frailty evaluation in this subgroup remain unclear. Methods: We used the Flatiron Health electronic record-derived de-identified database to source patients with incident MM diagnosed between January 1, 2011 and February 1, 2020. We compared clinical and demographic characteristics of patients ≥80y at the time of diagnosis with patients who were &amp;lt;80y of age. We abstracted baseline labs and cytogenetic data documented within 90 days from the start of first-line therapy. For those ≥80y, we captured the receipt of first line anti-myeloma therapy and examined early mortality (death within 6 months of diagnosis), derived progression-free survival (dPFS) and overall survival (OS) using Kaplan-Meier methods and Cox multivariate regression, with date of diagnosis as the index date. Finally, we compared dPFS and OS among potentially fit ≥80yo MM vs those between 75-79y, using ECOG performance status (PS) of zero as a surrogate marker of fitness status. Results: Of 8298 MM patients in this cohort, 1144 (13.5%) patients were ≥80y at diagnosis (median 81y, range 80-85y). Compared with the younger cohort, those ≥80y were more likely to be white, and have anemia, renal insufficiency, higher β2-microglobulin and higher stage at diagnosis. However, there was a lower prevalence of documented high-risk cytogenetic abnormalities, particularly high risk translocations (t4;14 and t14;16) even after adjusting for race/ethnicity (Mantel Haenszel OR=0.67; p 0.001). Common first line therapies included proteasome inhibitor (PI) + Immunomodulatory agent (Imid) based triplet (23%), Imid doublet (21%) and PI doublet (27%) (Table). Patients ≥80y received a median of 1 (IQR 1-2) lines of therapy, as opposed to those &amp;lt;80 (median 2, IQR 1-3). Overall, the outcome was significantly inferior among the ≥80y patients be those &amp;lt;80y (median dPFS 16 vs. 39 months, p&amp;lt;0.01; median OS: 26 vs 37 months, p&amp;lt;0.01; and 6-month mortality rate: 20.1% vs 6.2%, p&amp;lt;0.01). However, patients ≥80y and ECOG PS of 0 had similar 3y-dPFS (36.8 vs 33.1%; p=0.66) and 3y-OS (61.8 vs 65.2%; p=0.50) when compared to those between 75-79y with similar PS (ECOG PS of 0) (Figure). Conclusion: Patients 80y or above with newly diagnosed MM have distinct clinical and treatment characteristics as compared to their younger counterparts. Similar survival outcomes between older adults with good performance status vs their younger fit counterparts suggest the need for conducting a comprehensive frailty evaluation and individualized decision-making even in this cohort. Disclosures Giri: Carevive Systems: Honoraria; Pack Health: Research Funding; Carevive Systems: Research Funding. Costa:Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; Sanofi: Consultancy, Honoraria.

A Single Center Retrospective Analysis of Daratumumab, Pomalidomide, and Dexamethasone As a Second Line Therapy for Multiple Myeloma

A Single Center Retrospective Analysis of Daratumumab, Pomalidomide, and Dexamethasone As a Second Line Therapy for Multiple Myeloma

A Preliminary Assessment of HeterozygousCFHR3-CFHR1Deletion As a Permissive Mutation in Carfilzomib-Induced Atypical Hemolytic Uremic Syndrome

Carfilzomib is a critical chemotherapy medication used to treat patients with relapsed or refractory multiple myeloma. Unfortunately, drug-induced atypical hemolytic uremic syndrome (aHUS) has been established as a devastating and unpredictable side-effect of carfilzomib. Loss-of-function mutations in alternative complement pathway regulatory genes, such as complement factor H (CFH) and its related proteins (CFHRs), are the most frequently identified genetic abnormalities seen with aHUS. In our recently published work, two of three patients treated at the University of Rochester Medical Center for carfilzomib-induced aHUS were found to harbor the heterozygousCFHR3-CFHR1deletion, a genetic variant that is generally considered benign, implicating it in development of disease. We sought to further characterize the relationship between the heterozygousCFHR3-CFHR1deletion and development of carfilzomib-induced aHUS by conducting a case-control study. We screened banked frozen peripheral blood mononuclear cell (PBMC) samples from subjects treated with carfilzomib-based regimens at Washington University. Criteria for aHUS case selection were defined as all of the following: elevated LDH, decreased haptoglobin or elevated total bilirubin, evidence of schistocytes on peripheral blood smear, de novo anemia and thrombocytopenia, acute kidney injury, no evidence of infectious diarrhea (if tested), and active carfilzomib treatment at the time of disease. To ensure that controls had adequate exposure to carfilzomib, controls were selected from subjects who received ≥20 treatment cycles. Additional control selection criteria included: age &amp;gt;40 years, no evidence of hemolysis (LDH &amp;lt;250 U/L, total bilirubin &amp;lt;1.2 mg/dL), no de novo anemia or thrombocytopenia (hemoglobin &amp;gt;9 g/dL and platelets &amp;gt;100 x 109/L), and no chronic or acute kidney disease (creatinine &amp;lt;1.5 mg/dL). Ultimately, three cases of aHUS and four controls were identified. Corresponding PBMC samples were submitted to the Molecular Otolaryngology and Renal Research Laboratories for multiplex ligation-dependent probe amplificationCFH-CFHR5genomic region testing. We found that two of three case samples (4 of 6 total [67%], including the previously published cases), and two of four control samples (50%) harbored the heterozygousCFHR3-CFHR1mutation. No otherCFH-CFHR5genomic region mutations were detected. The frequency of heterozygousCFHR3-CFHR1deletion was not found to be significantly different between case and control groups. Given the large amount of carfilzomib exposure among the control group, this result suggests that the heterozygousCFHR3-CFHR1deletion is likely not a predisposing mutation in the development carfilzomib-induced aHUS. However, an adequately powered case-control study would be required to statistically rule-out the association. Disclosures Wildes: Seattle Genetics:Consultancy;Janssen:Research Funding;Carevive Systems:Consultancy.Lipe:Janssen:Membership on an entity's Board of Directors or advisory committees;GlaxoSmithKline:Membership on an entity's Board of Directors or advisory committees;Celgene:Membership on an entity's Board of Directors or advisory committees;Amgen:Membership on an entity's Board of Directors or advisory committees.

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy

Decision Making Factors That Influence Treatment Options for an Autologous Stem Cell Transplant for Older Adults (aged 65-75) with Newly Diagnosed Multiple Myeloma: A Mixed Methods Study

Background Multiple myeloma (MM) is an incurable hematological malignancy of older adults. Autologous stem cell transplant (ASCT) remains a standard of care with multiple retrospective and registry cohort studies demonstrating its efficacy in MM patients including older adults with the disease. Despite this favourable data, there remains wide heterogeneity in the utilization of ASCT, particularly among older adults with MM. We conducted a mixed methods study from the perspective of both oncologists and older adults with MM to: 1) identify decision making factors that influence ASCT eligibility and 2) to explore any barriers to ASCT utilization. Methods We conducted a mixed methods study at two academic centres and two community centres in Ontario, Canada. Older adults with MM (aged 65-75) who were within one year of treatment decision making regarding ASCT were invited to complete a survey from outpatient clinics. Oncologists (both community &amp; academic) were recruited via email. Semi-structured interviews were conducted with all participants who agreed to an interview. Thematic analysis was conducted to identify themes from the transcripts using NVivo (qualitative analytical software). The initial 3 transcripts were independently coded by two investigators, to develop a codebook. Any discrepancies were resolved using consensual validation. Once consensus was reached, the codes were then applied to the rest of the transcripts by one coder. A convergent parallel approach was used in combining the results of the qualitative and quantitative sections of the study. Results A total of 15 oncologists and 18 patients with MM completed the surveys. Baseline patient and oncologist characteristics are listed in Table 1. The majority of patients were offered an ASCT (78%) and among those offered, 79% went ahead with ASCT. Most patients were happy with the decision to either go ahead or refuse the transplant as indicated by a low decisional regret score (median of 5 and IQR of 0-19 out of 100, with a lower score indicating less regret with the decision). With regards to oncologists, 80% stated they were aware of geriatric tools to help with treatment risk stratification; however, the majority (75%) used none of these tools and relied on the 'eye-ball' test for decision making. Nine oncologists and 9 patients completed the semi-structured interview. Summarized themes identified are shown in Figure 1. From the perspective of patients, factors that most affected ASCT decision making were: strong trusting relationship with their oncologist (n=9), family support (n=9) and wanting the best treatment available (n=6). Top reasons to refuse ASCT were: fear of not recovering to baseline (n=2) and prolonged hospital stay (n=2). Oncologists identified using their clinical judgement (n=7), the belief that transplant was the best option (n=7) and lack of medical comorbidities (n=8), as the most important factors when recommending treatment. The lack of high quality randomized controlled trial data (n=9), local guidelines (n=5) and targeted assessment tools (n=7) were identified as barriers to ASCT. Notably, both patients (n=7) and oncologists (n=7) felt that ASCT decision making should not rely on chronological age alone. The findings of the qualitative and quantitative parts of the study concurred with each other and showed similar patterns. Conclusion To our knowledge, our study is the first to analyze contextual factors from the perspective of oncologists and older adults with MM that influence ASCT decision making and utilization. Despite guidelines supporting ASCT efficacy and safety among older adults with MM, our results demonstrate that the decision to undergo ASCT in older adults with MM is complex and variable both from the perspective of the patient and oncologist. Future incorporation of patient decision aids in parallel with enrollment of older adults in ASCT clinical studies and targeted geriatric assessments tools may provide an opportunity to enhance shared decision making and local guideline developments. Disclosures McCurdy: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Sanofi: Honoraria. Wildes:Carevive Systems: Consultancy; Janssen: Research Funding; Seattle Genetics: Consultancy. Mian:Sanofi: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy; Takeda: Consultancy, Honoraria.

Patient and Disease Factors Predict Risk of 1-Year Mortality Among Older Adults Who Receive Intensive Chemotherapy for Hodgkin Lymphoma (HL)

Background: Older patients with HL are often treated heterogeneously, with treatments ranging from palliative single-agent treatment to intensive dose-dense chemotherapy (Rodday, Br J Haematol, 2020). However, a proportion of patients are offered and administered potentially curative aggressive chemotherapy. There are scant data to guide the decision about which patients would benefit from this treatment approach. We developed and validated a model to predict 1-year mortality (overall survival) among older adults with HL who received intensive chemotherapy. WMethods: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked dataset. We included adults ≥65 years old who were diagnosed with classical HL between 2000-2012 and initiated full-regimen chemotherapy within 4 months of diagnosis. Full-regimen (i.e., aggressive) chemotherapy was defined by intent-to-treat as receiving a minimum of 2 cycles of a full regimen, with the option for 1 drug of a regimen to be omitted. Patients were followed for 1 year after diagnosis, or until death. WPrior to model development, we did a non-random 2:1 split by geographic region to create development and validation cohorts. Predictor variables of interest included patient demographics (age, sex, race/ethnicity, marital status); Charlson comorbidity index (CCI); disability status, a performance status proxy, as measured by previously established methods using claims (Davidoff, Med Care, 2014); disease characteristics (advanced vs. early stage; B symptoms; histology); and metropolitan geography. The primary outcome of our model was death within 1 yr of diagnosis, defined as a binary variable. We performed multiple imputation for variables with missing data to create 10 imputed datasets for each cohort. Using all candidate variables, we performed automated stepwise regression with p-value selection of 0.2 in each imputed dataset. Variables selected in at least 5/10 models were included in the final model, from which the c-statistic was derived. The development model was then applied to the validation cohort, and discrimination and calibration were performed to evaluate our model's performance. A final model was then fit using both cohorts with our selected variables from development. Analysis was done in Stata 16.1. WResults: Our cohort included 1,315 older HL patients (n=813 development, n=502 validation). Death occurred in 20% of patients in the development cohort and 17% in the validation cohort. Within the development cohort, a minority (&amp;lt;15%) of patients were Black or Hispanic. Two-thirds (64%) were married or partnered. Overall, 28% had a CCI of 0, and 13% of patients had disability. Among those within the development cohort, those with higher CCI, disability, advanced stage, B symptoms at diagnosis, and older age were more likely to die within 1 year of diagnosis. WWe identified missing data within the variables of B-symptoms (77/1315) and stage at diagnosis (310/1315), which we addressed using multiple imputation. Stepwise regression on the 10 imputed development datasets yielded the following variables for model inclusion: 1) age, 2) CCI, 3) B symptoms at diagnosis,4) advanced stage, and 5) lymphocyte depleted (LD) histology. We elected not to include LD histology in the final model due to high risk of misclassification and small number of patients with this HL subtype. The c-statistic for the development cohort was 0.70 (95% CI 0.66-0.75) (Figure 1). When applied to the validation dataset, this model yielded a c- statistic of 0.65 (95% CI 0.59-0.71). Calibration curve (Figure 2) revealed that predicted outcomes slightly exceeding observed outcomes. The final model was then fit on the two cohorts combined, shown in Table 1. Conclusions: We present a novel prediction model for 1-year mortality among older patients with HL who receive intensive chemotherapy. We found that older age, B-symptoms, advanced stage, and increased comorbidity predict death within 1 year of diagnosis. Our model is an initial step to help inform decision making for older patients and oncology providers who are weighing risks and benefits of aggressive chemotherapy among HL patients. In addition, we demonstrate that robust prediction modeling can be used to evaluate outcomes among older adults with hematologic malignancies prior to the initiation of treatment. Disclosures Evens: Seattle Genetics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Research To Practice: Honoraria, Speakers Bureau; MorphoSys: Consultancy, Honoraria. Friedberg:Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Portola Pharmaceuticals: Consultancy; Kite Pharmaceuticals: Research Funding; Roche: Other: Travel expenses; Seattle Genetics: Research Funding. Wildes:Carevive Systems: Consultancy; Janssen: Research Funding; Seattle Genetics: Consultancy. Parsons:Seattle Genetics: Consultancy.

Trajectory of Symptoms after Autologous Stem Cell Transplant Among Patients with Multiple Myeloma: A Population-Based Study

Introduction Autologous stem cell transplant (ASCT) remains the standard of care for eligible patients with multiple myeloma (MM). There is a paucity of data with regards to the symptom burden experienced by patients undergoing ASCT. In 2007, routine prospective collection of patient-reported outcome (PROs), Edmonton Symptoms Assessment System (ESAS), was initiated in all outpatient cancer clinics in Ontario, Canada. The ESAS is a validated and reliable tool which assess the severity across nine common symptoms: well-being, pain, tiredness, anxiety, depression, drowsiness, lack of appetite, nausea and shortness of breath. This administrative data provides a unique opportunity to the understand the symptom burden experienced by MM patients undergoing ASCT in the real world at a population level. Methods We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly diagnosed MM using the ICD-O-3 code 9732 (Multiple Myeloma), who received an ASCT within one year of diagnosis, between Jan 2007-Dec 2018, were identified. The main outcome of interest was an ESAS score of ≥4 each month, which has been shown to represent clinically significant moderate to severe symptom burden. Results A total of 2925 patients with myeloma were identified between 2007-2018. 158 patients who underwent a tandem ASCT and 956 patients who did not have an ESAS score recorded within a year following ASCT were excluded. Among 1969 (67.3%) evaluable patients, there were 12,820 unique ESAS assessments recorded during the first year which were used to form the cohort. The median number of ESAS surveys filled out by each patient was 5 (IQR 2-10) and the median time from transplant to first ESAS score recorded was 34 days (IQR 18-84). Baseline characteristics for the patients are shown in Table 1. The trajectory of symptoms following ASCT is shown in Figure 1. Tiredness, impaired well-being and lack of appetite were the three most common symptoms after ASCT and improved over the year. Psychosocial symptoms including anxiety and depression were present in approximately 20% of the cohort and only marginally improved during the year following ASCT. Additional analyses to assess the impact of baseline variables on high symptom burden is currently in progress. Conclusion This study represents the largest population-based cohort study done to date evaluating symptoms burden in patients with MM undergoing ASCT. Our results demonstrate that there is considerable symptoms burden during the first year following ASCT among MM patients. While physical symptoms improved over time, psychosocial symptoms remained persistent with only marginal improvement. Future studies aimed with tailored interventions are needed in order to address symptoms burden for patient groups at highest risk. Disclosures Mian: Amgen: Consultancy, Honoraria; Sanofi: Consultancy; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Pond:Takeda: Honoraria; Astra Zeneca: Consultancy; Roche Canada: Other. Wildes:Seattle Genetics: Consultancy; Janssen: Research Funding; Carevive Systems: Consultancy.

Symptom Burden in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: A Population-Based Study of Patient-Reported Outcomes

Introduction Multiple myeloma (MM) is an incurable malignant plasma cell disease with a median age at diagnosis of 70 years, making it a disease of older patients. Although there has been much progress made in the therapeutics of MM, there is a paucity of data with regards to the symptoms experienced by these patients. Patient reported outcomes (PROS) represent an opportunity to both understand the magnitude as well as the temporal trend of this symptom burden. In 2007, routine prospective collection of patient-reported Edmonton Symptoms Assessment System (ESAS) scores during all outpatient cancer clinic visits was initiated in Ontario, Canada. The ESAS is a validated and reliable tool that assesses the severity of nine common symptoms: well-being, pain, tiredness, anxiety, depression, drowsiness, lack of appetite, nausea and shortness of breath. The study of longitudinal data from an administrative data base provides a unique opportunity to understand the symptom burden experienced by MM patients in the 'real-world' at a population level. Methods We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly diagnosed multiple identified using the ICD-O-3 code 9732 (Multiple Myeloma), who received treatment, but no transplant in the first year, between the years Jan 2007-Dec 2018, were identified. The main outcome of interest was an ESAS score of ≥4 which has been shown to represent clinically significant moderate to severe symptom burden, within the first 12 months following MM diagnosis. Logistic regression was used to assess the association between baseline factors identified a priori and moderate to severe symptoms for each domain. Results A total of 4611 transplant ineligible patients with newly diagnosed myeloma were identified between the years 2007-2018. Of these, 2876 (62.3%) with at least one ESAS score following diagnosis were included in this analysis. This represented 27,701 unique ESAS assessments recorded during the first year, which were used to form the cohort. Baseline characteristics for transplant ineligible patients with one or more ESAS are shown in Table I. Trajectory for moderate to severe symptoms in each month following diagnosis is shown in Figure 1. A high proportion of the cohort reported moderate to severe symptoms at diagnosis, with tiredness (64%) and impaired well-being (60%) being among the most prevalent and nausea being the least prevalent (13%). Most symptoms decreased over the first year, with the largest decline happening in the first 3 months. One year following diagnosis, there continued to be a substantial burden of symptoms, with over 25% of the cohort reporting at least one or more of the following moderate-severe symptoms: tiredness, pain, impaired well-being, drowsiness or loss of appetite. Self-reported depression rates marginally decreased over time; however, at the end of one year, 18% of cohort still reported moderate to severe depression. On multivariable analysis, younger age, female sex, urban geographic location, poor socioeconomic status, an earlier diagnosis year, myeloma defining end-organ damage and non-teaching hospital were associated with a higher odds of reporting moderate to severe symptoms. Conclusion Our results demonstrate that there is considerable symptom burden during the first year following MM diagnosis, with tiredness, impaired well-being and pain being the most common. Although symptoms improve over time, a significant proportion of patients continue to experience moderate to severe symptoms one-year post diagnosis. This study represents the largest population-based cohort study done to date in symptom burden among patients with MM. Future studies aimed at targeted intervention are needed early in the disease course in order to alleviate symptoms burden for at-risk patient groups. Disclosures Mian: Takeda: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Pond:Roche Canada: Other; Astra Zeneca: Consultancy; Takeda: Honoraria. Wildes:Janssen: Research Funding; Seattle Genetics: Consultancy; Carevive Systems: Consultancy.

Improving patient-reported measures in oncology: a payer call to action.

Despite rising interest in integrating the patient voice in value-based payment (VBP) models for oncology, barriers persist to implementing patient-reported measures (PRMs), including patient-reported performance measures (PR-PMs). This article describes the landscape of oncology PRMs and PR-PMs, identifies implementation barriers, and recommends solutions for public and private payers to accelerate the appropriate use of PRMs in oncology VBP programs. Our research used a multimethod approach that included a literature review, landscape scan, stakeholder interviews and survey, and a multistakeholder roundtable. The literature review and landscape scan found that limited oncology-specific PR-PMs are available and some are already used in VBP programs. Diverse stakeholder perspectives provided insight into filling current gaps in measurement and removing implementation barriers, such as limited relevance of existing PRMs and PR-PMs for oncology; methodological challenges; patient burden and survey fatigue; and provider burden from resource constraints, competing priorities, and insufficient incentives. Key recommendations include: (a) identify or develop meaningful measures that fill gaps, engaging patients throughout measure and program development and evaluation; (b) design programs that include scientifically sound measures standardized to reduce patient and provider burden while supporting care; and (c) engage providers using a stepwise approach that offers resources and incentives to support implementation. DISCLOSURES: Funding for this project was provided by the National Pharmaceutical Council. Schmidt, Perkins, Riposo, and Patel are employees of Discern Health, a consulting firm with many clients, including government, life sciences, nonprofit, and provider organizations. Valuck is a partner at Discern Health. Westrich is an employee of the National Pharmaceutical Council, an industry-funded health policy research group that is not involved in lobbying or advocacy. Basch reports grants from National Cancer Institute and Patient-Centered Outcomes Research Institute; fees from serving as a consultant on research projects at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, and Research Triangle Institute/CMS; and fees from serving as a scientific advisor to CareVive Systems, Sivan Healthcare, Navigating Cancer, and AstraZeneca, outside the submitted work. McClellan reports fees from serving on the boards of Johnson & Johnson and Seer Bio and as an advisor to Cota outside the submitted work; and McClellan is an independent board member on the boards of Cigna and Alignment Healthcare, co-chair of the Guiding Committee for the Health Care Payment Learning and Action Network, and receives fees for serving as an advisor for MITRE, outside the submitted work.

1497P - JNJ-61186372 (JNJ-372), an EGFR-cMET bispecific antibody, in advanced non-small cell lung cancer (NSCLC): An update on phase I results

Background: JNJ-372 has demonstrated activity in EGFR and cMET-driven tumor models. In an ongoing phase 1 study of JNJ-372 in patients (pts) with advanced NSCLC, 1050 mg was identified as a recommended phase 2 dose in dose escalation (Part 1) and is being explored in the dose expansion of pts with EGFR-mutated (mut) NSCLC (Part 2). Methods: Pts were treated with JNJ-372 IV weekly x 4W for cycle 1, then biweekly thereafter. Pharmacokinetic (PK) sampling was taken at multiple time points for all pts in Part 1 and for the first 6 pts in Part 2. Disease evaluations were performed every 8 weeks. Tumors were characterized at baseline through next-generation sequencing of ctDNA and/or tumor tissue. Results: As of April 13th, 2018, 55 pts received JNJ-372 in Part 1 (n = 30) or Part 2 (n = 25), with 21 pts (38%) continuing therapy. Median age was 63y, 40% were male, 96% were Asian, and median prior systemic therapies was 2. The most frequent (≥15%) adverse events (AEs) were infusion-related reaction (56%), rash/acneiform dermatitis (53%), dyspnea (20%), paronychia (24%), nausea (22%), constipation (18%), stomatitis (18%), decreased appetite (18%), pruritus (16%), fatigue (16%), and peripheral edema (16%). AEs were mostly grade 1-2, with 3 ≥grade 3 treatment-related AEs (myalgia, neutropenia, and peripheral edema, all grade 3). PK was linear and dose proportional at doses ≥350 mg, with faster clearance PK at the 140-mg dose. Of the 30 response-evaluable pts with EGFRmut disease, treated at doses ≥700 mg, there are 8 partial responses (PRs; 4 confirmed PRs). This includes 6 pts with L858R or Exon19del primary mutations, and acquired resistance to first and/or third-generation EGFR tyrosine kinase inhibitors (TKIs), and 2 pts with primary Exon20ins disease. Activity was also observed in 2 pts with EGFRwt disease (squamous cell carcinoma and pleomorphic adenocarcinoma), each with -20% change in sum of largest diameter. The longest duration of treatment was 13.6 months. Conclusions: JNJ-372 is a novel EGFR-cMET bispecific antibody with a manageable safety profile consistent with EGFR and cMET inhibition. Preliminary evidence suggests JNJ-372 can have activity in EGFR-driven NSCLC, including pts resistant to EGFR TKIs. Clinical trial identification: NCT02609776 First posted: November 20, 2015. Editorial acknowledgement: Writing support was provided by Tracy T. Cao, PhD of Janssen Global Services, LLC. and funded by Janssen Global Services, LLC. Legal entity responsible for the study: Janssen Research & Development. Funding: Janssen Research & Development. Disclosure: B.C. Cho: Research funding: Janssen, Novartis, AstraZeneca, Yuhan, Champions Oncology, Abbvie, Dong-A ST, Ono, MOGAM; Honoraria: AstraZeneca, Novartis, MSD, Ono, Roche; Consulting or Advisory role: Janssen, AstraZeneca, Novartis, MSD, Roche, Yuhan; Speakers’ bureau: Novartis J-Y. Han: Research funding: Roche. E. Haura: Research funding: Lilly, Novartis, Boehringer Ingelheim, Janssen, Ignyta, Forma Therapeutics; Consulting or Advisory role: Janssen; Patent: Patent pending on PLA technology related to kinase inhibitor sensitivity biomarkers; Travel/Accommodations: Bristol-Myers Squibb, Roche. J. Bauml: Research funding: Merck, Novartis, Carevive Systems, Janssen, Bayer; Consulting or Advisory Role: Clovis, Bristol-Myers Squibb, Celgene, Boehringer-Ingelheim, AstraZeneca, Genentech, Guardant Health. R.E. Sanborn: Research funding: Merck (investigator-initiated study), Bristol-Myers Squibb (institutional research support), MedImmune (institutional research support); Honoraria: AstraZeneca; Consulting or Advisory Role: AstraZeneca, Seattle Genetics, Takeda, Genentech, Abbvie, Celldex; Travel/Accommodations: Janssen. M. Curtis, E. Attiyeh, N. Haddish-Berhane, K. Bae, R. Knoblauch, L. Sherman, M.V. Lorenzi: Employment: Janssen Stock: Johnson & Johnson. All other authors have declared no conflicts of interest.

Race Is Associated with Bortezomib but Not Lenalidomide Utilization during First-Line Treatment of Multiple Myeloma

Background: It was once believed that African-American (AA) patients (pts) with multiple myeloma (MM) had more aggressive disease; however, recent studies suggest that undertreatment rather than biology is responsible for the poorer outcomes observed among AA pts. We recently reported that the utilization of stem cell transplants and bortezomib (BTZ) was 37% and 21% lower, respectively, among AA Medicare beneficiaries from 2000-2010 (Fiala & Wildes, Cancer, 2017). The data suggested that, had AA pts received these treatments at similar rates as their white counterparts there would have been no disparity in outcomes. As they did not, AA pts had a 10% increased risk for death. Lenalidomide (LEN), like BTZ, has become one of the primary treatments for MM since its approval in 2007. However, pts often incur significantly higher out of pocket costs on oral chemotherapies such as LEN compared to injectables like BTZ. Thus, we hypothesized that disparities in utilization of LEN would be greater than in BTZ.Methods: To test our hypothesis, all MM cases from 2007-2013 in the SEER-Medicare were reviewed along with corresponding claims through 2014. We excluded cases with incomplete records including those not enrolled in Medicare Part A, B, and D, and HMO enrollees. We also excluded cases where MM was diagnosed prior to age 65 and suspected cases of smoldering MM, pts who did not receive MM treatment and did not have diagnostic codes for CRAB criteria as previously described (Fiala, et al, under review). The presence or absence of claims for LEN and BTZ within 6 months following MM diagnosis was used to determine utilization. Multivariate logistic regression was performed to analyze the impact of race on LEN and BTZ utilization controlling for age at diagnosis, sex, year of diagnosis, Medicaid enrollment, and previously established algorithms of poor performance status [PS] indicators and Charlson Comorbidity Index [CCI] score.Results: 6,285 cases were included in the analysis. The median age at MM diagnosis was 76 years and 50% were female; 77% of cases were white, 16% were black, and 6% were another race. Overall, the utilization of LEN and BTZ during first-line treatment was 28% and 38%, respectively. In the multivariate model, race was not associated with LEN utilization, but BTZ utilization was reduced by 24% (aHR 0.76; 95% CI 0.65-0.90; p 0.0009) among AA pts. Overall, the models of LEN and BTZ were similar (Table 1). Advancing age, Medicaid enrollment and poor PS were associated with decreased utilization; more recent diagnosis increased utilization. CCI was associated with LEN but not BTZ utilization, sex with BTZ but not LEN.Discussion: We originally hypothesized that LEN utilization would be reduced among AA pts based on increased out-of-pocket costs. However, we and other researchers have shown that traditional access barriers such as insurance and income only account for about 25% of health disparities (Fiala & Wildes, Cancer, 2017). We now hypothesize LEN's oral administration may mitigate some other factors that have been shown to increase disparities such as the preferences and biases of pts and providers. For example, AA pts may prefer oral therapies to a greater extent than white pts. Or AA pts who may decline injectable chemotherapy due to distrust in the medical system may be more willing to accept an oral formulation, or providers who hold an unconscious bias may be more willing to offer one.An alternative explanation could be that AA pts, who tend to have more comorbidities and poorer overall health at MM presentation (Fiala, et al, 2015 ASH abstract 5618), were more likely to be candidates for LEN rather than other treatments. However, we do not believe this is the case as poor PS and increasing CCI were associated with decreased LEN utilization.Conclusions: AA race was associated with reduced utilization of BTZ but not LEN for first-line treatment of MM. These findings do not support our original hypothesis that LEN is associated with a greater disparity in utilization than BTZ due to the higher cost sharing involved with oral chemotherapies. Whether oral formulations mitigate other barriers to treatment such as the preferences and biases among pts and providers requires future study. [Display omitted] DisclosuresAilawadhi:Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Vij:Jazz: Honoraria; Konypharma: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Abbvie: Honoraria; Janssen: Honoraria; Bristol-Meyers-Squibb: Honoraria. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy.