Treatment Patterns from 2009 to 2015 in Patients with Newly Diagnosed Multiple Myeloma in the United States: A Report from the Connect® MM Registry

Abstract Introduction: Between 2009 and 2015, use of novel therapies (immunomodulating drugs and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time frame may help project near-term future treatment patterns. Connect® MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed MM (NDMM). Pts with NDMM were enrolled in 2 sequential cohorts from Sep 2009 to Apr 2016. This noninterventional registry did not prescribe or limit therapy choices. Study sites represented all census regions, with 89% and 11% split between community and academic sites, respectively. This allowed a reasonable generalizability to patterns for the US. Methods: Connect® MM enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493 NDMM pts from Sep 2009 to Dec 2011, and Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at a baseline visit and quarterly visits thereafter until death or discontinuation. The current analysis was conducted for the population of treated pts (N=2848) as of May 2016. This study examined recorded treatment choice of first-line regimen, maintenance therapy, and second-line regimen in 6-month intervals. Trends in regimens were graphically represented using "Tepee" plots (Srinivasan, Shankar. Resource Tepee. Patent US 7,495,673 B1. 24 Feb 2009). Briefly, all pts who initiated treatment during each 6-month interval are represented horizontally, with each horizontal line indicating 100% of all treatment used in that period. The regimens are represented by gray shading with wider bands signifying the more frequently used regimens at each time interval. Results: Median follow‐up for all pts was 39.3 months (0.03‐78.4) in Cohort 1 and 15.4 months (0.2-40.1) in Cohort 2. For the treated population, the median age was 67 years (range 24‐94), 58% were male, 83% were white, and 38% of those reporting International Staging System stage had stage III MM. By US geographical region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 80.2%) were from community sites, and 397 (13.9%) were from academic sites with the remaining from government sites. A total of 1416 (47.4%) reported an intent to transplant (stem cell transplant [SCT]) at the initiation of therapy. A total of 666 (25.8%) have progressed and entered second line. Tepee plots of treatment patterns for start of induction for those pts with and without SCT intent are provided in Figure 1A and 1B, respectively. The year 2012 does not feature in these induction plots, as this period corresponds to a time when pts were not enrolled-Cohort 1 had been completed and Cohort 2 had not yet opened. The 4 most common induction regimens for SCT intent, from left to right, in order of decreasing frequency of use, were lenalidomide (R), bortezomib (V), dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 5 most common induction regimens for those without SCT intent, from left to right, in order of decreasing frequency of use, were VD, RD, RVD, CyBorD, and V. Triplet therapy in first-line induction pts increased in frequency from 2009 to 2014. The 4 most frequent maintenance regimens for those with SCT intent were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for pts who did not intend to receive SCT were R monotherapy, RD, VD, and V monotherapy. The most prevalent regimens in the second line were VD, RD, V, and RVD. Additional graphs including treatment patterns by age group (≤ 70 vs > 70 years) and maintenance by conduct of first-line SCT will be presented. Conclusions: Our work utilizes Tepee plots to outline induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional registry study in the US. Triplet therapy use increased in the time period studied, with RVD being the most frequently used triplet for pts with or without SCT intent. The most common maintenance regimens included R as monotherapy or in combination. Disclosures Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen/ONYX: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Gasparetto:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria. Jagannath:Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Terebelo:Celgene: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene: Consultancy. Kitali:Celgene: Employment, Equity Ownership. Zafar:Celgene: Employment. Srinivasan:Celgene: Employment; Individual Patent: Patents & Royalties: US7,495,673B1 Used for MM-Connect Treatment Patterns Abstract.. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Real-World Evidence on Treatment Utilization in Lower-Risk Myelodysplastic Syndromes: Findings from a Medical Record Review in the United States

Blood ◽

10.1182/blood-2021-145576 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4666-4666

Author(s):

Ulrich Germing ◽

Ravi K. Goyal ◽

Aylin Yucel ◽

Rohan C. Parikh ◽

Maria Jimenez ◽

...

Keyword(s):

Board Of Directors ◽

Lower Risk ◽

Research Funding ◽

The United States ◽

Full Time ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

The Us

Abstract Introduction: Patients diagnosed with myelodysplastic syndromes (MDS) are at an increased risk for developing infections, bleeding events, cardiopulmonary complications, and progressing to acute myeloid leukemia (AML). Patients with lower-risk MDS experience a mean life-year loss of about 6 years, and the main focus of treatment is on management of cytopenias, in particular anemia. Currently, limited real-world evidence exists on prevailing treatment patterns and outcomes in lower-risk MDS in the United States (US). Methods: In this retrospective, non-interventional review of medical records, eligible patients (≥ 18 years of age) with diagnosis of lower-risk MDS (with or without ring sideroblasts and with single-lineage or multilineage dysplasia) between July 1, 2013 and September 30, 2018, were identified by participating clinicians. Patients with prior history of AML or other malignant neoplasms were excluded. This is an ongoing study in the US and interim data are described. Study measures descriptively summarized patient demographics, clinical characteristics at MDS diagnosis, and utilization of medication treatments for the management of anemia. Results: Data from medical records of 50 patients with lower-risk MDS were abstracted by 26 hematologist-oncologists in the US. Participating clinicians had been managing treatment for hematology/oncology patients for an average (standard deviation [SD]) of 16.3 (6.7) years, 53.9% practiced in an academic hospital or cancer center, and 46.2% practiced in a community setting. The mean (SD) age for patients with lower-risk MDS at diagnosis was 64.2 (9.9) years, 64.0% were male, 70.0% were White, and 60% were insured primarily through Medicare. Most patients (54.0%) had Low-risk MDS (as categorized by Revised International Prognostic Scoring System) followed by Very low-risk (28.0%), and Intermediate-risk (18.0%) at initial diagnosis. The most common gene mutations observed were JAK2 (22.0%) and ASXL1 (8.0%). The most common karyotype abnormalities observed were del(5q) (28.0%), −Y (14.0%), and del(7q) (12.0%). During the 12 months before diagnosis of lower-risk MDS, cardiac complications were observed among 18.0% of patients, and 58.0% of patients were either current or former smokers at the time of diagnosis of lower-risk MDS. At the time of data abstraction, mean (SD) follow-up time was 39.6 (21.6) months, and 46 (92.0%) patients had received ≥ 1 line of treatment for MDS-associated anemia. Of these 46 patients, 93.5% received first-line treatment with an erythropoietin-stimulating agent (ESA). In the first-line, most patients received ESA monotherapy (n = 37; 80.4%) followed by ESA-based combination therapy (n = 6; 13.0%), lenalidomide only (n = 2; 4.4%), and azacitidine (n = 1; 2.2%). All 18 patients who received a second-line treatment had received an ESA-based first-line treatment. Second-line treatments received were ESA-based treatment (n = 5; 27.8%), lenalidomide only (n = 5; 27.8%), luspatercept only (n = 4; 22.2%), azacitidine only (n = 3; 16.7%), and filgrastim only (n = 1; 5.6%). Third-line treatment was only observed in 3 patients. Conclusions: In this ongoing study, current analysis for 50 patients with lower-risk MDS in the US showed ESA-based regimens were the most common first-line therapy. ESA-based treatment was again utilized as second-line therapy among some patients who were previously treated with ESA. Disclosures Germing: Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding. Goyal: RTI Health Solutions: Other: Full-time employee of RTI Health Solutions, which is business unit of RTI International, a non-profit research organization, which received funding from BMS to conduct this study.. Yucel: BMS: Current Employment, Current holder of individual stocks in a privately-held company. Parikh: RTI-Health Solutions: Other: Full-time employee of RTI-HS, which received funding to conduct this study from BMS.. Jimenez: RTI Health Solutions: Current Employment. Sluga-O'Callaghan: RTI Health Solutions: Current Employment. Tang: Bristol-Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Hughes: BMS: Current Employment. Diez-Campelo: Takeda Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Physicians' Behavior, Diagnostics and Treatment Patterns in Multiple Myeloma Management in Belarus: Nation-Wide Survey

Blood ◽

10.1182/blood-2018-99-111127 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5853-5853

Author(s):

Ihar Iskrou ◽

Anatoly Uss ◽

Sergey Golubev ◽

Vitali Papok

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Board Of Directors ◽

Plasma Cells ◽

Treatment Patterns ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

First Line Treatment

Abstract Background: Although multiple myeloma (MM) remains an incurable disease, its management progressed during the last decade owing to novelties in diagnostics and new therapeutic options. There is a general belief in heterogeneity of the novel technologies penetration among countries and regions, such differences should be studied. Information on physicians' knowledge, preferences and satisfaction is limited worldwide and may provide important insights for explanation of differences in clinical decision making in routine practice. Moreover, data on typical diagnostic and treatment patterns in real-world clinical setting are particular scarce in the Eastern European and Eurasian region. Methods: A cross-sectional national survey of physicians treating MM in Belarus was performed from October 2017 till January 2018. Among 51 hematologists registered in the country 43 physicians involved in MM management in real clinical settings were approached. Printed forms of 21-item questionnaire containing multiple choice questions were used. We anonymously collected physicians' opinions on typical diagnostics and treatment patterns as well as their clinical reasoning, preferences and satisfaction. We assessed whether practice place and type, practical experience (length of service and average number of MM patients seen per year) and attitude to participation in clinical trials influence answers. Univariate analysis was conducted with Fisher's exact test. Results: All approached physicians completed the survey. Among respondents 17 (40%) belonged to republican specialized centers, 37 (86%) were hospital-based physicians, 23 (53%) had more than 10 years of service, 28 (65%) seen more than 20 MM patients per year. 10 (23%) declared their experience in clinical trials and 20 (46%) had no experience but expressed readiness to be involved in. The clinical uptake of revised ISS for MM was 33%, among adopters physicians with more than 10 years in practice and who sees more than 20 patients per year dominated. The proportions of ISS users which believed that median survival for low-risk, standard-risk and high-risk MM patients to be > 12 months were 100%, 100% and 36%, respectively. For primary MM diagnosis 40% of respondents used MRI and 49% - CT-imaging. Physicians used the next criteria for treatment response : < 5% plasma cells (PCs) in bone marrow (88%), Ig level normalization (74%), absence of clonal PCs in BM (60%), and absence of new lesions (37%). The possibility to perform autologous stem-cells transplantation (ASCT) was revealed as a key factor for first-line treatment choice. Various bortezomib-based regimens were predominant treatment options for first-line treatment of patients eligible for ASCT. Melphalan-containing regimens were more widely spread as first-line treatment of ASCT-ineligible patients. The majority of respondents (52%) practiced first-line treatment of more than 4 months of duration, while 41% of clinicians used second-line therapy of short duration (less than 6 months). In the relapse setting after ASCT the most common regimens were still bortezomib-based as well as schemes with bendamustine. In the second-line setting in patients who did not receive ASCT monotherapy was more commonly reported. In absence of high dose dexamethasone for oral use Belarusian physicians preferred treatment schemes with combination of drugs for IV and per os routes of administration. The predominant factors of drug choice were efficacy (91%) and cost (97%). The respondents reported satisfaction with current situation in diagnostics and treatment in 74% and 65% of cases, respectively. The factors influencing readiness for disease management change were clinical experience, hospital-based practice position and positive attitude to/participation in clinical trials. Conclusions: The study covers the gaps of information about real-world MM management in Belarus. The Belarusian physicians are aware about the modern place of ASCT in MM. Targeted education in specific aspects of MM management (disease biology understanding, clinical guidelines updates, risk evaluation and stratification) may result in wider adoption of innovative diagnostic approaches and treatment technologies. MM management should be further concentrated in large specialized clinical centers for plasma cells disorders. The survey results make possible and warranted further intercountry comparisons. Disclosures Iskrou: Takeda Belarus: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer Belarus: Consultancy, Honoraria, Speakers Bureau; Novartis Belarus: Consultancy, Honoraria, Speakers Bureau; Nativita Belarus: Consultancy, Honoraria, Speakers Bureau; Octapharma Belarus: Consultancy, Honoraria, Speakers Bureau. Uss:Roche Belarus: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda Belarus: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Golubev:Medical department of Takeda Belarus: Employment. Papok:Medical department of Takeda Belarus: Employment.

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A Phase III Study to Determine the Efficacy and Safety of Lenalidomide in Combination with Melphalan and Prednisone (MPR) in Elderly Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.613.613 ◽

2009 ◽

Vol 114 (22) ◽

pp. 613-613 ◽

Cited By ~ 17

Author(s):

Antonio Palumbo ◽

Meletios A. Dimopoulos ◽

Michel Delforge ◽

Martin Kropff ◽

Robin Foa ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Board Of Directors ◽

Primary Endpoint ◽

Interim Analysis ◽

Newly Diagnosed ◽

Efficacy And Safety ◽

Time To Progression ◽

First Line ◽

Advisory Committees

Abstract Abstract 613 Background: Lenalidomide (Revlimid®) is an oral immunomodulatory agent with clinical efficacy in patients with multiple myeloma (MM). In patients with relapsed/refractory MM, lenalidomide plus dexamethasone improved time to progression (TTP) and overall survival (OS) in comparison with dexamethasone alone. In newly diagnosed MM patients, the current study compares the efficacy and safety of melphalan, prednisone and lenalidomide (MPR) with that of MP alone. Methods: Key inclusion criteria were: ≥65 years of age, newly diagnosed and symptomatic MM. 459 patients were randomly assigned to receive MPR followed by lenalidomide maintenance therapy or MPR followed by placebo maintenance therapy or MP followed by placebo maintenance therapy (Figure 1). The study induction and maintenance phases were followed by an open label lenalidomide extension and a follow-up phase. All patients received aspirin 100 mg/day as thrombo-prophylaxis. The primary endpoint of the study is progression free survival (PFS). The secondary endpoints are OS, time-to-progression, response rate, time to response, response duration, time-to-next anti-myeloma therapy, safety, quality of life and exploratory assessment of cytogenetic abnormalities. Primary comparison is based on the intent-to-treat population comparing PFS between MPR followed by lenalidomide with MP followed by placebo; secondary comparisons are between MPR followed by lenalidomide and MPR followed by placebo, and between MPR followed by placebo and MP followed by placebo. Results: The first patient was enrolled in February 2007. A pre-planned interim analysis to evaluate the efficacy and safety was performed at 50% information. An independent central adjudication committee determined the assessment and timing of progressive disease prior to the interim analysis. At the interim analysis, it was determined by the Data Monitoring Committee (DMC) that the study had crossed the O'Brien Fleming superiority boundary for the primary endpoint, demonstrating a highly statistically significant improvement in PFS for patients treated with MPR compared with MP as first-line treatment for MM patients. The topline results will be availabel at the time of the meeting. Conclusions: MPR is an effective and safe regimen for front-line use in MM. PFS was significantly improved in patients who received MPR followed by lenalidomide maintenance compared with those who received MP followed by placebo maintenance. MPR followed by lenalidomide maintenance is a new therapeutic option and can be considered a new standard for patients older than 65 years old. Disclosures: Palumbo: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide is not approved for first line use in multiple myeloma. Dimopoulos:Celgene: Honoraria. Delforge:Janssen-Cilag: Consultancy, Honoraria; Celgene: Honoraria, Speakers Bureau. Kropff:Ortho Biotech: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Foa:Celgene: Membership on an entity's Board of Directors or advisory committees. Yu:Celgene: Employment. Herbein:Celgene: Employment. Mei:Celgene: Employment. Jacques:Celgene: Employment. Catalano:Celgene: Research Funding.

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The Ki67/CD138 Ratio Independently Predicts Overall Survival in the Upfront Treatment of Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.2016.2016 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2016-2016

Author(s):

Tomer M Mark ◽

Peter Forsberg ◽

Ihsane Ouansafi ◽

Adriana C Rossi ◽

Roger N Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Board Of Directors ◽

Research Funding ◽

Complete Response ◽

Newly Diagnosed ◽

First Line ◽

Advisory Committees ◽

Line Therapy

Abstract Background: Assessment of malignant plasma cell cycling via plasma cell labeling index (PCLI) has been a validated prognostic tool in multiple myeloma (MM) but the test requires specialized technical expertise and is not widely available. Ki67 is a well-known protein marker of cellular proliferation on immunohistochemical (IHC) staining with prognostic utility in other malignancies. In an effort to develop a simpler system to provide analogous information to PCLI, we used a novel IHC co-staining technique for CD138 and Ki67 to quantify plasma cells in active cycling. We then performed a retrospective analysis of the ratio of Ki67/CD138 (Ki67%) in newly diagnosed patients with multiple myeloma receiving 1st-line therapy to correlate with clinical outcomes. Methods: A retrospective cohort study of patients (pts) with treated symptomatic MM was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital. For inclusion in the analysis, subjects must have started first-line treatment in the period of 2005-2010, and had available bone marrow biopsies. Double-staining with Ki67 and CD138 was performed by IHC. The Ki67% was calculated as the percent of plasma cells expressing CD138 that were also found to express Ki67. Treatment outcomes were stratified and compared based on %Ki67. Response was determined by monthly serum protein electrophoresis / immunofixation (IFX) with free light chain analysis according to International Multiple Myeloma Working Group (IMWG) guidelines. Pts who were IFX negative but had no subsequent bone marrow biopsy were classified as being in unconfirmed complete remission. Results: We identified 151 patients with newly diagnosed MM and available %Ki67 expression who received first-line therapy over the period of 2005-2010. Patient were subdivided into two groups based on %Ki67: Low: %ki67 <= 5%, n = 87; and High: %Ki67 >5, n=64, to allow for comparison of treatment response and survival analysis. Specific therapeutic agent exposure history did not differ significantly between patients. Both groups had similar depth of response rates (ORR) to front-line therapy, Table 1. Median progression-free survival for the high versus low %Ki67 groups approached statistical significance at 54 months (95% CI 30.8,67.4) versus 26.9 months (95% CI 21.6,40.2), respectively (P = 0.083). At data cut-off, there were 30 deaths in the low %Ki67 group (1-yr OS 93%, 5-yr OS 71%) and 36 deaths in the high %Ki67 group (1-yr OS 94%, 5-yr OS 62%). Median overall survival (OS) was not reached for Ki67% <= 5% (95% CI 97.3,NR) vs. 78.9 months (95% CI 55.9,93.1) for Ki67% > 5%, (P = 0.0434), Figure 1. Multivariate cox regression for factors with influence on OS showed that only high-risk cytogenetics (HR 2.05, 95% CI 1.17, 2.92, P = 0.027), ISS (HR 1.835, 95% CI 1.33, 3.60, P = 0.000), and %Ki67 group status had an independent effect on survival outcome. Low (<=5%) versus high (>5%) %Ki67 influenced overall survival with a hazard ratio of 1.76 (CI 1.07,2.92, P = 0.027). Survival after ASCT was significantly longer in the low %Ki67 group with median OS not reached (95%CI, 97.3, NR) versus 86.9 months (95% CI 43.9, NR) for high %Ki67 group (P = 0.04). Discussion: The ratio of IHC double positive Ki67 and CD138 of > 5% is an independent prognostic marker for overall survival in newly diagnosed MM undergoing 1st line therapy. The %Ki67 serves as a simpler and widely available analog to PCLI that can be presently performed in most hematopathology laboratories. Table 1: First Line Treatment and Best Response (modified IMWG Criteria) Ki67% <= 5(N = 87)n (%) Ki67% > 5(N = 64)n (%) P Treatment Exposure* Lenalidomide 59 (67.8) 48 (75) 0.34 Thalidomide 30 (34.5) 14 (21.9) 0.09 Bortezomib 25 (28.7) 14 (21.9) 0.34 Alkylating agent 11 (12.6) 4 (6.3) 0.19 ASCT 27 (31) 22 (34.4) 0.66 Best Response Overall Response (>= Partial response) 77 (88.4) 57 (89.1) 0.41 Complete response 15 (17.2) 22 (34.4) Unconfirmed complete response** 14 (16.1) 8 (12.5) Very good partial response 23 (26.4) 15 (23.4) Partial response 25 (28.7) 12 (18.8) Stable disease 9 (10.3) 5 (7.8) Progressive disease 1 (1.2) 2 (3.1) * Percentages do not add to 100% due to instances of concurrent therapy use ** Unconfirmed complete response: immunofixation negative, but no confirmatory bone marrow biopsy available Figure 1 Overall Survival by %Ki67 Figure 1. Overall Survival by %Ki67 Disclosures Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Perry:Celgene: Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Early Prediction of Treatment Response in Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-111624 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3159-3159

Author(s):

Moritz Binder ◽

S. Vincent Rajkumar ◽

Martha Q. Lacy ◽

Morie A. Gertz ◽

Francis K. Buadi ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Treatment Cycle ◽

Validation Cohort ◽

Newly Diagnosed ◽

First Line ◽

Advisory Committees ◽

Training Cohort ◽

M Spike

Abstract Background: The introduction of several novel agents has led to an improvement in response rates and survival outcomes in patients with newly diagnosed multiple myeloma. Despite significant therapeutic advances a subset of patients with multiple myeloma do not achieve a deep response to first-line treatment and biomarkers are needed to identify those at risk. Methods: We studied 472 patients with newly diagnosed multiple myeloma who were treated in clinical practice (n = 280, training cohort) or on prospective clinical trials (n = 192, validation cohort) at Mayo Clinic between 12/2003 and 12/2015. All patients had measurable disease (M-spike ≥ 1.0 g/dL) and received treatment with novel agents. Serum M-spike and free light chains (FLC) were measured before and after the first treatment cycle. The outcome of interest was the best response to first-line treatment (evaluated using the International Myeloma Working Group Uniform Response Criteria). Failure to achieve a deep response was defined as not achieving a very good partial response or better. The serum parameters of interest were the relative decrease in M-spike and absolute free light chain difference (ΔFLC). The Wilcoxon signed-rank test was used to compare the serum parameters before and after the first treatment cycle. Logistic regression models were used to assess the associations between the change in serum parameters after the first treatment cycle and best response to first-line treatment. P-values below 0.05 were considered statistically significant. Results: The median age at diagnosis in the training and the validation cohort were 67 (32 - 94) and 66 years (41 - 86), respectively. One hundred eighty one (65%) and 103 patients (54%) were male, respectively. The three most common regimens in the training cohort were lenalidomide + dexamethasone, lenalidomide + cyclophosphamide + dexamethasone, and bortezomib + lenalidomide + dexamethasone. In the validation cohort, the three most common regimens were carfilzomib + thalidomide + cyclophosphamide, lenalidomide + cyclophosphamide + dexamethasone, and ixazomib + cyclophosphamide + dexamethasone. In the two cohorts, the median baseline M-spike decreased from 3.1 g/dL (1.0 - 10.0) to 1.7 g/dL (0.0 - 6.6) and 3.2 g/dL (1.0 - 8.5) to 1.4 g/dL (0.0 - 4.5) after the first treatment cycle, respectively (p < 0.001 for both comparisons). The median baseline ΔFLC decreased from 31.1 mg/dL (0.0 - 2269.7) to 5.4 mg/dL (0.0 - 785.8) and from 23.3 mg/dL (0.1 - 3579.6) to 4.3 mg/dL (0.0 - 1139.3) after the first treatment cycle, respectively (p < 0.001 for both comparisons). M-spike reduction < 50% during the first treatment cycle was associated with failure to achieve a deep response: OR 4.54 (95% CI 2.72 - 7.58, p < 0.001) in the training cohort and OR 6.68 (95% CI 3.42 - 13.03, p < 0.001) in the validation cohort. Patients with reduction in M-spike < 10% during the first treatment cycle experienced failure to achieve a deep response in 86% (25/29) and 100% (10/10), respectively. ΔFLC reduction < 50% during the first treatment cycle was associated with treatment failure to achieve a deep response: OR 4.83 (95% CI 2.83 - 8.25, p < 0.001) in the training cohort and OR 5.09 (95% CI 2.37 - 10.92, p < 0.001) in the validation cohort. Patients with reduction in ΔFLC < 10% during the first treatment cycle experienced failure to achieve a deep response in 83% (34/41) and 91% (19/21), respectively. Conclusions: Early changes in M-spike and ΔFLC are strong predictors of response to treatment. We established and prospectively validated two readily available biomarkers that can identify patients at risk for treatment failure and may inform treatment decisions in newly diagnosed multiple myeloma. Disclosures Lacy: Celgene: Research Funding. Gertz:Physicians Education Resource: Consultancy; janssen: Consultancy; Teva: Consultancy; Alnylam: Honoraria; Research to Practice: Consultancy; Apellis: Consultancy; Medscape: Consultancy; annexon: Consultancy; Abbvie: Consultancy; celgene: Consultancy; Prothena: Honoraria; Ionis: Honoraria; Amgen: Consultancy; spectrum: Consultancy, Honoraria. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Russell:Vyriad: Equity Ownership. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Kumar:Celgene: 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; KITE: 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.

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Effect of Autologous Transplantation on PFS2 in Myeloma Patients Receiving Front-Line Bird (clarithromycin, lenalidomide, dexamethasone)

Blood ◽

10.1182/blood.v124.21.5778.5778 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5778-5778

Author(s):

Ekta Aneja ◽

Adriana C Rossi ◽

Tomer M Mark ◽

David Jayabalan ◽

Roger Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Board Of Directors ◽

Research Funding ◽

Second Line ◽

Newly Diagnosed ◽

Advisory Committees ◽

Line Therapy ◽

Progression Of Disease

Abstract Background: BiRd (clarithromycin, lenalidomide, dexamethasone) combination therapy yields >90% overall response rates in newly diagnosed patients with symptomatic multiple myeloma (MM). Long term follow up of the phase II BiRd study revealed 49% of patients went on to receive autologous hematopoietic stem cell transplants (ASCT), either as consolidation or salvage. Here we evaluate progression free survival 2 (PFS2) and overall survival (OS) in our cohort of patients, and assess the impact of ASCT. Methods: Seventy-two patients with newly diagnosed MM were enrolled on the BiRd trial between Dec 2004 and Nov 2006. BiRd is lenalidomide 25mg PO daily (d1-21), clarithromycin 500mg PO BID, dexamethasone 40mg PO weekly, for 28 day cycle. Patients remained on BiRd until progression of disease, consolidation with autologous stem cell transplant (ASCT), or unacceptable toxicity, and all continued to be monitored through subsequent lines of therapy. We performed a retrospective chart review of all patients enrolled in the BiRd trial. PFS2 was defined as the time elapsed from start of BiRd until progression of disease on 2nd line therapy. Results: With over 8 years of follow up, 6 patients remain on continuous BiRd, 28 received ASCT consolidation, and another 6 received ASCT as salvage. Nine patients died on induction therapy and the remaining patients received second line chemotherapy. Patients were stratified by no ASCT, consolidation ASCT and salvage ASCT. Median PFS2 was 98 months, 94 months, and 53 months, respectively (p<0.22). Twenty-three patients died during second line therapy. Median OS was not reached, 102 months, and 55 months respectively (p<0.92). Discussion: Advances in the treatment of patients with multiple myeloma over the past decade have introduced increasing numbers of therapeutic options, improving survival considerably. While multiple myeloma is still considered an incurable disease, patients today will likely receive several lines of therapy. The contribution and timing of each option must be considered. In our cohort of patients, receiving ASCT in the salvage setting trended toward shorter PFS, however failed to reach statistical significance. Consolidation with ASCT in our patient cohort did not translate into survival advantage. The optimal timing and utility of ASCT in the era of novel agents and increasing treatment options warrants further review, and is an area of active investigation. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Rossi: celgene: Speakers Bureau; millenium: Speakers Bureau. Mark:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Speakers Bureau. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Real-World Treatment Patterns and Adverse Events in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib in the UK: A Preliminary Analysis

Blood ◽

10.1182/blood-2019-123025 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5885-5885

Author(s):

Jing Xie ◽

Alan Yong ◽

Catherine Waweru ◽

Thuy Anh Sorof ◽

Ravi K Goyal ◽

...

Keyword(s):

Board Of Directors ◽

Preliminary Analysis ◽

Research Funding ◽

Treatment Patterns ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

The Uk

Introduction: Bruton tyrosine kinase (BTK) is a critical component of the B-cell receptor pathway, and is a validated target for the treatment of chronic lymphocytic leukemia (CLL). Ibrutinib is a first-generation, covalent, small molecule BTK inhibitor approved for the treatment of CLL. We present a preliminary analysis of treatment patterns and adverse events (AEs) in patients with CLL treated with ibrutinib in a real-world setting. Methods: A retrospective chart review is being conducted among patients diagnosed with CLL and treated with ibrutinib in oncology centers throughout the UK; the target sample size for the study is 250 patients. Patients are eligible if they initiated ibrutinib after diagnosis of CLL, between January 2017 and June 2018, with at least 12 months of follow-up data available, with the exception that patients who died less than 12 months after ibrutinib initiation remained eligible. Hematology/oncology physicians reviewed medical records and completed web-based data collection forms. Baseline medical history information and data on treatment characteristics and AEs were collected. By June 2019, a total of 151 medical records (60% of the target sample size) had been abstracted. All analyses were descriptive in nature and were performed in SAS v9.4 or later (Cary, NC, USA). Results: Twenty-two physicians from specialist cancer centers or tertiary referral treatment centers (45.5%), teaching hospitals (31.8%) and non-teaching hospitals (22.7%) submitted data on ibrutinib-treated patients. The median follow-up for this interim sample of 151 patients was 16.1 months (range: 2.8-27.5 months) from ibrutinib initiation (index date) and 61.7 months (range: 11.6-264.1 months) from initial CLL diagnosis (Table 1). Median age was 71 years, 56% were male, 22.5% of patients had del(17p) mutation and 24.5% had TP53 mutations/aberrations. Of the 151 patients, 24.5% (n=37) initiated ibrutinib as first-line therapy while 75.5% (n=114) initiated ibrutinib as second- or later-line treatment. Median time to initiation of ibrutinib was 3.8 months (range: 0.3-123.7 months) for first-line therapy after initial CLL diagnosis and 22.3 months (range: 0.2-242.2 months) for second-line therapy after end of first-line therapy. Other therapies that patients received besides ibrutinib included the combination of fludarabine, cyclophosphamide, and rituximab (first-line, 22.5%; second-line, 1.7%), bendamustine plus rituximab (first-line, 19.9%; second-line, 15.5%), and chlorambucil plus rituximab (first-line, 10.6%; second-line, 1.7%). The most common AEs observed during ibrutinib therapy were bruising (19.9%), cytopenias (18.5%), diarrhea (15.2%), and arthralgia (11.3%) (Table 2). Conclusion: This preliminary analysis describes patient characteristics and treatment patterns in ibrutinib-treated patients in the UK. We found that the majority of ibrutinib use was in the second-line or later, reflecting the current UK public reimbursement situation. AEs such as bruising and cytopenias were commonly reported in patients treated with ibrutinib, and future analyses from this study will determine how these AEs and others affect dosing, treatment discontinuation and healthcare resource utilization. Disclosures Xie: AstraZeneca: Employment. Yong:AstraZeneca: Employment, Equity Ownership. Waweru:AstraZeneca: Employment, Equity Ownership. Sorof:Acerta Pharma: Employment. Goyal:RTI Health Solutions: Employment. Davis:RTI Health Solutions: Employment. Follows:Roche: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau. Hillmen:Apellis: Research Funding; Gilead: Research Funding; Roche: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees.

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Real-world treatment patterns and outcomes of triple-exposed multiple myeloma patients treated in community oncology practices in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18727 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18727-e18727

Author(s):

Robert Smith ◽

Mei Xue ◽

Natalie Dorrow ◽

Prateesh Varughese ◽

Cosima Hogea ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Real World ◽

Proteasome Inhibitors ◽

Office Visit ◽

The United States ◽

Subsequent Treatment ◽

Treatment Patterns ◽

Duration Of Therapy ◽

The Us

e18727 Background: Treatment for multiple myeloma (MM) over the past decade has significantly improved survival. In particular, 3 drug classes have altered the treatment paradigm for MM patients: proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies (anti-CD38s). Despite these advances, the majority of patients with MM will become refractory to PIs, IMiDs, and anti-CD38s, and limited evidence indicates these patients have poor outcomes. A retrospective study in the US showed that 275 patients treated at 14 academic institutions with prior exposure to a PI, IMiD, and anti-CD38 had median overall survival of 9.2 months. The aim of this study was to evaluate real-world treatment patterns and outcomes (duration of therapy and overall survival) of patients who had been treated with a PI, IMiD, and anti-CD38 in community practices in the US. Methods: This retrospective observational study was conducted using the Integra Connect (IC) database. The IC database includes electronic health data from structured and unstructured fields from 12 community practices on the East and West Coast of the US. Adult patients with ≥2 ICD-9/ICD-10 codes for MM on at least 2 separate dates, who received MM treatment between Jan 1, 2016, and Dec 31, 2019, with treatment history that included at least one PI, one IMiD, and one anti-CD38 (triple exposed), and initiated a subsequent line of therapy (s-LOT) after becoming triple exposed, were included. Duration of length of s-LOT was defined as number of days from start of s-LOT to last-day supply of s-LOT. Overall survival was defined as the length of time from start of s-LOT through death or the date of the last office visit. Results: A total of 501 patients were included in this analysis. The median age of patients was 64.9 years; 50% were male; 50% had commercial insurance. 82.8% of patients had ECOG 0 or 1 at diagnosis and had received a median of 3 prior lines of therapy (LOTs) before initiating s-LOT. Prior to initiating s-LOT, 91% had been exposed to bortezomib, 81% to carfilzomib, 94% to lenalidomide, 82% to pomalidomide, and 100% to daratumumab. In s-LOT, 95% received treatment that included same drug or same drug class (30% received bortezomib, 48% carfilzomib, 31% lenalidomide, 47% pomalidomide, and 31% daratumumab). The median duration of s-LOT was 78 days and median survival was 10.3 months (308 days) from initiation of s-LOT. Conclusions: For triple-class exposed patients, there is a lack of consensus on the most efficacious approach to subsequent treatment. The present study shows a significant amount of retreatment with previously used agents or classes among these patients with short duration of therapy and poor survival. As has been previously noted, new strategies and agents targeting novel aspects of MM are needed to improve outcomes for these patients. Disclosures: This study (213286) was sponsored by GlaxoSmithKline.

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Evolving Unmet Need in Patients Refractory to Lenalidomide: Overview of the Clinical Trials in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2020-142642 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Maria-Victoria Mateos ◽

Rohan Medhekar ◽

Istvan Majer ◽

Mehmet Turgut

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Literature Review ◽

Board Of Directors ◽

Unmet Need ◽

Publicly Traded ◽

First Line ◽

Advisory Committees ◽

Line Of Therapy

Introduction: The majority of newly diagnosed multiple myeloma (NDMM) patients are currently treated with lenalidomide-based regimens as their first line of therapy. This trend is likely to continue in the coming years. Typically, lenalidomide is administered until disease progression and has significantly contributed to better outcomes in these patients. However, most patients relapse, and prognosis worsens with each relapse. The choice of optimal treatment for patients who relapse while receiving lenalidomide as first line of therapy is unclear. Moreau et al (Blood Cancer J. 9, 38 [2019]) concluded that there is limited data on approved combinations for treating these patients and are restricted by the low number of lenalidomide-refractory patients enrolled in the pivotal trials. Results from the ongoing clinical trials of the combination of carfilzomib and anti-CD38 antibodies were not available at the time of the Moreau et al publication. The aim of this targeted literature review was to include this new data and to summarize currently available evidence on progression-free survival (PFS) for the treatment of RRMM patients who progressed on lenalidomide-based regimens. Methods: A targeted literature review was conducted to identify registrational clinical trials in patients with RRMM reporting PFS outcomes. PubMed, congress proceedings, and product labels were searched between Jan 2014 to July 2020. In addition to PFS, demographic, disease characteristics and treatment history were extracted for the trial populations to contextualize potential variations in study outcomes. The regimens studied in these trials were classified as lenalidomide-based, proteasome inhibitor (PI)-based and pomalidomide-based. Number of prior lines of therapy, prior exposure and refractoriness to lenalidomide and bortezomib were reported. Results: Twelve registrational trials were identified based on the search criteria (Table 1). Most pivotal trials assessing lenalidomide-based regimens (POLLUX, ELOQUENT-II, TOURMALINE-MM1) except the ASPIRE trial excluded patients who were refractory to lenalidomide. Trials evaluating PI-based regimens (e.g., CANDOR) or pomalidomide-based regimens (e.g., OPTIMISMM) included these patients, with more recent studies enrolling a larger proportion. Percentage of lenalidomide-exposed (and lenalidomide refractory) ranged from 40% (32%) in CANDOR to 98% (90%) in ELOQUENT III. These studies also enrolled a larger proportion of patients who were bortezomib-exposed, although most of these patients were at first relapse, with the exception of ELOQUENT III and ICARIA where most patients were at third relapse. Among lenalidomide-refractory patients, the median-PFS (mPFS) observed for the pomalidomide-based regimens ranged from 9.5 to 10.1 months and that observed for PI-based regimens ranged from 4.9 to 25.7 months. PFS in the lenalidomide-refractory subgroup was considerably shorter than in the ITT population. The mPFS for patients receiving carfilzomib/daratumumab/dexamethasone (KDd; CANDOR) and isatuximab/carfilzomib/dexamethasone (IsaKd; IKEMA) was not reached at median follow-up of 16.9 and 20.7 months respectively. While the mPFS for (KDd) for lenalidomide-refractory patients in CANDOR trial was not yet reached at median follow up of 16.9 months; the mPFS of 25.7 months for KDd in the MMY-1001 trial appears to be the longest among the assessed regimens. Conclusion: Patients refractory to lenalidomide have shorter PFS and represent a population with high unmet need. This targeted literature review suggests that the PI-based KDd regimen provides longer PFS compared to other lenalidomide-sparing regimens in lenalidomide-refractory populations. Heterogeneity across trial populations may limit the comparability of these treatments. Disclosures Mateos: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; GlaxoSmithKline: Consultancy. Medhekar:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Majer:Amgen (Europe) GmbH: Current Employment, Current equity holder in publicly-traded company.

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Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽

10.1182/blood-2019-126205 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3129-3129

Author(s):

Hans C. Lee ◽

Sikander Ailawadhi ◽

Cristina Gasparetto ◽

Sundar Jagannath ◽

Robert M. Rifkin ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Causes Of Death ◽

Age Groups ◽

Treatment Patterns ◽

Age Group ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

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