Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France

Background. Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk. Methods. A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization. Results. Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months). Conclusions. The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies.

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Real-World Treatment Patterns And Clinical Outcomes In Er+/Her2- Metastatic Breast Cancer: Results From A Multicountry Retrospective Medical Record Review

Value in Health ◽

10.1016/j.jval.2016.03.1644 ◽

2016 ◽

Vol 19 (3) ◽

pp. A137 ◽

Cited By ~ 1

Author(s):

D Mitra ◽

S Kurosky ◽

G Zanotti ◽

JA Kaye

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Medical Record ◽

Clinical Outcomes ◽

Real World ◽

Metastatic Breast ◽

Treatment Patterns ◽

Medical Record Review ◽

Record Review ◽

Retrospective Medical Record Review

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Real-World Clinical Outcomes By Cytogenetic Risk Category in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in France

Blood ◽

10.1182/blood.v128.22.4784.4784 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4784-4784

Author(s):

Huamao Mark Lin ◽

Keith L Davis ◽

James A. Kaye ◽

Katarina Luptakova ◽

Lu Gao ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Partial Response ◽

Research Funding ◽

Complete Response ◽

Line Treatment ◽

Second Line ◽

High Risk Patients ◽

Risk Patients ◽

Standard Risk

Abstract INTRODUCTION: Multiple Myeloma (MM) is an incurable hematologic cancer characterized by multiple recurrences. With each recurrence, patients have a lower probability of response and duration of response is shorter. Therefore, there is an unmet need to improve outcomes in relapsed/refractory multiple myeloma (RRMM). There is a shortage of data describing clinical features and outcomes in these patients in real-world practice, particularly with regard to differences in outcomes by baseline cytogenetic risk. To help address this information gap, this study analyzed data from a cohort of RRMM patients in France. METHODS: A retrospective observational review of medical records was conducted in a cohort of 200 patients with RRMM in France. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 40 hematology/oncology providers across France practicing mainly in academic hospitals. Inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) first-line (induction) regimen of chemotherapy with or without stem cell transplant (SCT) and with or without other post-induction/SCT therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients could be alive or deceased at the time of record abstraction. Baseline cytogenetic risk was defined as follows: high-risk: cytogenetic abnormalities del(17p), t(4:14), or t(14;16); unknown/unassessed risk: patients for whom cytogenetics were unavailable; or standard-risk: all patients with known cytogenetics not classified as high-risk. Patients were assessed for treatment response, overall survival (OS) and progression-free survival (PFS) from date of first relapse (study index date). All analyses were descriptive. Survival was assessed using the Kaplan-Meier (K-M) method. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. A total of 55 high-risk and 113 standard-risk patients were identified; risk category was unknown or unassessed for 32 patients. Among all patients, mean (SD) age at RRMM diagnosis was 66.3 (8.9) years and 62% of the sample was male. Lenalidomide + dexamethasone was the most common second-line systemic regimen initiated (50% of high-risk patients, 59.5% of standard-risk patients receiving second-line treatment). A total of 114 patients (57%) initiated a third-line treatment. Despite clinical response in second-line treatment occurring sooner in high-risk patients (median: 106 days) than in standard-risk patients (median: 237 days), physician-assessed overall response rate (ORR) was lower in high-risk patients (63%: 17% complete response, 46% partial response) than standard-risk patients (91%: 26% complete response, 65% partial response) across all second-line treatments combined (Table 2).. For third-line treatment, ORR was lower in high-risk patients (54%: 12% complete response, 42% partial response) than standard-risk patients (74%: 9% complete response, 65% partial response). Among patients who initiated a second-line treatment (n = 192), 47.4% were deceased at the time of data collection. From second-line initiation, K-M estimates of 1- to 5-year OS and PFS were substantially lower for high-risk patients versus standard-risk. Specifically, the proportions of patients still alive 1, 3, and 5 years after second-line treatment initiation were 73%, 51%, and 36%, respectively, for high-risk patients and 94%, 73%, and 61% for standard-risk patients. The proportions of patients without disease progression at 1, 3, and 5 years after second-line initiation were 48%, 13.5%, and 5% for high-risk patients and 82%, 42%, and 14% for standard-risk patients. CONCLUSIONS: The importance of cytogenetic risk classification as a prognostic factor in RRMM was apparent in this retrospective review, in which patients with high-risk cytogenetics had less favorable outcomes in terms of ORR, OS, and PFS than standard-risk patients. Decreased response rate and lower PFS and OS was documented among patients with high-risk cytogenetics, which is in contrast to shorter time needed to achieve best clinical response in this subgroup. Results from this real-world study provide further confirmation of the unmet medical need presented by RRMM, especially for patients with high-risk cytogenetics. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Gao:Takeda: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

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Real-World Treatment Patterns and Outcomes of Patients with Functional High-Risk (Early Relapse) Multiple Myeloma

Blood ◽

10.1182/blood-2020-142629 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 17-18

Author(s):

Andrew J. Belli ◽

Eric Hansen ◽

Ankit Kansagra ◽

Keshava Dilwali ◽

Ching-Kun Wang

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Real World ◽

Treatment Patterns ◽

Practice Setting ◽

Private Company ◽

Early Relapse ◽

High Risk Patients ◽

Risk Patients ◽

Insight Into

Background: There have been significant advancements in the treatment of multiple myeloma (MM) over the last 20 years including an influx of recently approved novel therapies. However, with these advances in treatment, the optimal combination and sequence of agents remain largely unknown especially in relapsed/refractory MM. A major unmet need in MM is patients with high-risk disease. Revised International Staging System is used to identify patients with high-risk MM, however a better definition of high risk includes "functional high risk" (i.e. patients relapsing within 18 months from diagnosis). As it has been previously shown that clinical trial populations are not universally representative of those in the routine practice setting, real-world data (RWD) can provide valuable insight into this rapidly evolving treatment landscape and high-risk population. Here we explore treatment patterns and outcomes of functional high-risk MM, patients who relapse within 18 months of initial diagnosis. Methods: This retrospective study utilized the COTA real-world database, a de-identified database of RWD derived from the electronic health records of partnered healthcare providers in the United States. A total of 958 patients were identified as having been diagnosed with active MM between Jan. 1, 2015 and Jan. 1, 2020 and experienced early relapse (defined as relapse within 18 months of initial active MM diagnosis and treatment). Practice setting distribution of this cohort was 84% academic and 16% community. Line of therapy was assigned programmatically utilizing IMWG definitions and guidelines. Patient characteristics and treatment patterns across the first (1L) and second lines (2L) of treatment were assessed using descriptive statistics. Time to next treatment (TTNT) was calculated overall and within treatment subgroups of interest as a surrogate for progression-free survival. Results: Among this functional high-risk patient population, the mean age was 64 yrs. (SD ±11.3) and the patients were predominantly white (72.6%). The most common cytogenetic abnormalities at diagnosis were del(13) (46.0% positive), 1q (36.4%), and t(11;14) (25.4%). In 1L, the majority of patients received a triplet regimen (75.4%), most commonly proteosome inhibitor (PI) + immunomodulator (IMiD) + steroids (45.0%). A total of 56 patients (5.9%) received stem-cell transplant (SCT) in 1L. Overall, 16.3% of the population did not receive 2L therapy due to death. Among the patients who received 2L therapy after early relapse (N=869), 50.5% received an SCT. TTNT was significantly longer for patients receiving SCT in 2L as compared to those who did not (34.8 vs. 5.8 months, respectively). Among patients who did not receive SCT (N=430), triplet therapy was most common (61.2%) with PI + IMiD + steroids representing the largest regimen group (30.2%). Table 1 shows the distribution of PI drugs within the 2L PI + IMID + steroids group and their associated median TTNT. No significant differences were observed when comparing median TTNT of 2L PI + IMID + steroids to daratumumab-based regimens (5.3 vs. 5.6 months, respectively). Conclusions: In our real-world population, median TTNT for functional high-risk patients was 17.8 months. 50.5% of these functional high-risk patients received SCT in 2L with the most common induction regimen containing cyclophosphamide + etoposide + dexamethasone (CED). For patients not receiving SCT in 2L, the most common regimen type included PI + IMID + Steroids. In comparing antibody-based therapy vs. PI + IMID + dexamethasone-based therapy, daratumumab-based combinations showed no significant difference in unadjusted analysis. Our study highlights some very important observations in functional high-risk patients. First, if patients are SCT eligible and it is not performed as part of first line treatment, SCT still provides the best outcomes in regard to TTNT in the second line setting. For patients not receiving SCT, our RWD demonstrates that 30.2% receive PI + IMID + dexamethasone as 2L treatment with only 13% receiving carfilzomib-based combination. Our study highlights the poor outcome of functional high-risk patients and provides insight into treatment patterns in 2L therapy. Further research is needed to explore patient and disease characteristics of functional high-risk patients and study novel treatment strategies like CAR T cell therapy or T-cell engagers in these patient population. Disclosures Belli: COTA, Inc.: Current Employment, Current equity holder in private company. Hansen:COTA, Inc.: Current Employment, Current equity holder in private company. Kansagra:Alnylam Pharmaceuticals, Bristol Myers Squibb /Celgene, GlaxoSmithKline, Janssen, Pharmacyclics, Takeda Pharmaceuticals, Pfizer, Karyopharm Therpeutics: Other: Advisory Board. Dilwali:COTA, Inc.: Current Employment, Current equity holder in private company. Wang:COTA, Inc.: Current Employment, Current equity holder in private company.

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Real-world treatment patterns for platinum-sensitive recurrent serous ovarian cancer: Findings from a multinational medical record review.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e16548 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e16548-e16548

Author(s):

Jerzy Tyczynski ◽

Sarah Williams ◽

Noolie Gregory ◽

Mandy Garratt ◽

Ilian Tchakov ◽

...

Keyword(s):

Ovarian Cancer ◽

Medical Record ◽

Real World ◽

Treatment Patterns ◽

Medical Record Review ◽

Serous Ovarian Cancer ◽

Platinum Sensitive ◽

Record Review

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Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20557 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20557-e20557

Author(s):

Eric Leon Tam ◽

David Joseph Iberri ◽

Michaela Liedtke ◽

Lori S. Muffly ◽

Parveen Shiraz ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Maintenance Therapy ◽

Proteasome Inhibitor ◽

Post Transplant ◽

Risk Patients ◽

To Receive ◽

Standard Risk

e20557 Background: The ideal choice of maintenance therapy in patients with HRMM high-risk multiple myeloma remains unknown. We analyzed the outcomes of patients with HRMM undergoing transplant receiving different maintenance approaches. Methods: Patients with MM undergoing their first ASCT from 2012-19 within 1 year of diagnosis were identified from the prospectively maintained database of patients undergoing ASCT. HRMM was defined as having t(4;14), t(14;16), t(14;20), del17p13, or gain 1q detected on fluorescent in situ hybridization (FISH). Results: Of the 412 patients undergoing ASCT within 1 year of diagnosis, 333 had FISH data available and of these, 37% (124/333) patients had high-risk cytogenetics. Distribution of HR cytogenetics was as follows: deletion 17p: 37% (n = 46), t(4;14): 27% (n = 34), t(14;16) or t(14;20): 12% (n = 26), gain1q: 31% (n = 41). 9% (n = 12) had more than one HR abnormality. In patients with HRMM, median age at transplant was 59 years (range: 39 to 73), and 61% (n = 103) were males. 64% (n = 107) of high-risk patients received post-transplant maintenance therapy. Maintenance therapy in this group included a proteasome inhibitor (PI) in 34% (n = 29), immunomodulatory drug (IMiD) in 59% (n = 51), or both in 7% (n = 6). There was no difference in baseline characteristics of HRMM patients receiving PI vs. IMiD maintenance, except that patients with del17p were more likely to receive PI maintenance therapy (55% vs 28%, p = 0.01). (Table) After a median follow-up of 3.1 years from diagnosis, patients with HRMM had inferior PFS compared to patients with standard risk disease, with median PFS of 3 vs. 4.8 years, p < 0.001. Amongst the 86 HRMM patients receiving maintenance therapy, median PFS in patients receiving PI vs. IMiD vs. both PI + IMiD maintenance was 3 vs. 3.2 vs. 2.2 years, respectively, log-rank p = 0.7. In the sub-group of patients with 17p deletion, median PFS in the three groups was 3 vs. 2.9 vs. 2.2 years, respectively, log-rank p = 0.7. Conclusions: Patients with HRMM have inferior PFS compared to patients with standard risk disease. We observed similar outcomes in HRMM patients post-transplant regardless of the choice of maintenance therapy. [Table: see text]

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The real-world outcomes of multiple myeloma patients treated with daratumumab

PLoS ONE ◽

10.1371/journal.pone.0258487 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258487

Author(s):

Agoston Gyula Szabo ◽

Tobias Wirenfeldt Klausen ◽

Mette Bøegh Levring ◽

Birgitte Preiss ◽

Carsten Helleberg ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Real World ◽

Randomized Clinical Trials ◽

Proteasome Inhibitors ◽

Median Number ◽

The Real ◽

Treatment Timing ◽

Risk Patients ◽

Standard Risk

Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001). Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.

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Evaluation of Functional and Cytogenetic High-Risk Multiple Myeloma Using Real-World Data

Blood ◽

10.1182/blood-2021-149724 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4093-4093

Author(s):

Ankit Kansagra ◽

Eric Hansen ◽

Andrew J. Belli ◽

Stefanie Goran ◽

Ching-Kun Wang

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Disease Progression ◽

Real World ◽

Multivariate Analyses ◽

Rapid Disease Progression ◽

High Risk Patients ◽

Risk Patients ◽

High Risk Populations ◽

Equity Ownership

Abstract Introduction: Multiple myeloma (MM) is a heterogeneous disease with wide variability in outcomes. The presence of cytogenetic abnormalities in MM is of critical importance for prognosis and risk stratification. However, patients who may or may not have sufficient cytogenetic abnormalities to classify as high-risk can still experience rapid disease progression despite therapy, or functional high risk (FHR) disease. These two high risk cohorts comprise vulnerable subpopulations who have a significant burden of disease, and it is critical that we understand the underlying patient characteristics and optimal treatment sequence. We sought to investigate these two high risk patient populations treated in the contemporary real-world practice setting. Methods: A total of 1719 patients were identified in the COTA real-world database as having been diagnosed with active MM on or after January 1, 2015 and classified as either FHR, cytogenetic high risk (CHR), or both. The COTA real-world database is a USA-based real-world evidence database comprised of longitudinal, Health Insurance Portability and Accountability Act (HIPAA)-compliant, data on the diagnosis, clinical management, and outcomes of patients with cancer. Of the 1719 patients, 1260 were identified to be FHR, defined as relapse <18 months from initial active MM diagnosis. A total of 459 patients were identified as CHR, among which 347 were both FHR and CHR. CHR was defined as a patient having at least one of the following abnormalities: t(4;14), t(14;16), t(14;20), del(17p), 1q gain, or hypoploid. Line of therapy was applied programmatically using an algorithm based on International Myeloma Working Group criteria and clinical guidance. The primary outcome was time to next treatment (TTNT) calculated using the Kaplain Meier method. Univariate and multivariate analyses were conducted to understand predictors of rapid disease progression among high-risk patients. Results: In our real-world population, FHR patients tended to be slightly younger, African American, and treated predominantly in the academic setting (Table 1). First-line (1L) and second-line (2L) treatment patterns by category are shown in Table 2. A lower proportion of FHR patients received 1L immunomodulators as compared to the other high-risk groups, while almost half of the CHR patients received 1L stem cell transplant (SCT). In 2L, among patients not receiving 2L SCT, a higher proportion of CHR patients received a daratumamab-based treatment as compared to FHR (23.2% vs. 12.0%, respectively). We observed a longer median (95% CI) TTNT for high-risk patients receiving 2L daratumamab-based treatment as compared to patients who did not: 8.5 months (6.4-13.0) vs. 6.0 months (5.3-6.9), p=0.07 (Figure 1). Univariate and multivariate analyses showed age at diagnosis (HR: 0.98, CI: 0.97, 0.99), normal cytogenetics (HR: 0.78, CI: 0.63, 0.97), 1L immunomodulator (HR: 0.39, CI: 0.22, 0.69), 1L proteasome inhibitor (HR: 1.4, CI: 1.1, 1.8), and 1L SCT (HR: 0.22, CI: 0.15, 0.32) as significant predictors of rapid disease progression. Conclusions: Our study provides important insights comparing high risk populations with MM treated in the real-world setting. A higher proportion of CHR patients received 1L SCT and this provided the longest 1L TTNT as compared to other treatments. In 2L, among patients not receiving 2L SCT, we observed a trend towards significantly longer TTNT provided by dara-based treatment as compared to non-dara based treatment; however, our TTNT is lower than progression-free survival results observed in pivotal trials. We identified potential underlying differences in our patient populations that may be driving the predictors of rapid disease progression, including 1L SCT eligibility and renal disease, and these will be further investigated in propensity score matched populations. Future research will continue to explore optimal treatment sequences in high-risk populations with multiple myeloma to improve patient outcomes. These data highlight an urgent need to better predict FHR patients at diagnosis and develop clinical trials incorporating novel compounds in high risk patients. Figure 1 Figure 1. Disclosures Hansen: COTA, Inc.: Current Employment. Belli: COTA, Inc.: Current Employment, Other: Equity ownership. Goran: COTA, Inc.: Current Employment. Wang: COTA, Inc.: Current Employment, Other: Equity ownership.

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Real World Assessment of Treatment Patterns and Outcomes Among Multiple Myeloma Patients across Different Risk Stratification Criteria in the United States: A Retrospective Cohort Study

Blood ◽

10.1182/blood-2021-147439 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1640-1640

Author(s):

Motiur Rahman ◽

Christopher Kim ◽

Jazmine Mateus ◽

Alissa Keegan

Keyword(s):

High Risk ◽

Risk Stratification ◽

Real World ◽

Treatment Initiation ◽

Treatment Patterns ◽

Community Practice ◽

Newly Diagnosed ◽

The Us ◽

Standard Risk

Abstract Background: Despite the development of highly active novel agents, high risk (HR) multiple myeloma (MM) patients continue to demonstrate relatively poor prognosis. Limited data is published on how treatment patterns with risk stratification systems have changed over time. Moreover, real world studies using electronic health records (EHRs) have not evaluated the performance of risk stratification systems with real world outcomes. This study aims to evaluate the ability to implement three different risk stratification systems - international staging system (ISS), revised ISS (R-ISS), and high-risk chromosomal abnormalities (HRCA, defined as presence of del(17)p, t(4;14) and/or t(4;16)) [Palumbo et al. 2015] - to characterize treatment patterns and associated outcomes [real world overall survival (rwOS) and real world progression free survival (rwPFS)] among newly diagnosed MM (NDMM) patients in the US community practice. Methods: This study used Flatiron Enhanced MM EHR de-identified database (New York, NY). Newly diagnosed MM patients (≥ 18 years) were diagnosed from January 2015 through June 2020 (cohort 1 - for studying treatment distribution) with follow-up through December 2020, and from January 2015 through December 2018 (cohort 2 - for rwOS and rwPFS), with follow-up through December 2020. Patients with malignancies other than MM were excluded. Proportion of rwOS was measured from treatment initiation until death, and median rwPFS was measured from treatment initiation until death, progression, or start of new line of therapy using Kaplan-Meier method. Results: A total of 1,979 and 1,382 patients were eligible in cohorts 1 and 2, respectively. In both the cohorts, approximately 18% (cohort 1: N=367, cohort 2: N=248), 41% (cohort 1: N=805, cohort 2: N=566), and 37% (cohort 1: N=738, cohort 2: N=508) were HR patients according to the R-ISS, ISS, and HRCA criteria, respectively. Approximately half of the HR patients were ≥70 years old (52% for R-ISS III and ISS III, and 47% for HRCA), with chronic kidney disease stage ≥3 by eGFR for 54% R-ISS III and ISS III, and 34% high risk CA, and ECOG score ≥2 for 18% R-ISS III, 19% ISS III, and 14% HRCA patients. Triplets were the most frequent treatment regimens (62% for R-ISS III and II, and 66% for R-ISS I; 59% for ISS III, and 65% for ISS II and I; 65% for HRCA and 61% for standard risk CA(SRCA) with proteasome inhibitors (PIs) / immunomodulatory agents (IMiDs) / dexamethasone being most common regimen across all the risk stratification criteria. Quadruplet agent use was higher in R-ISS III and ISS III categories (6.8% vs. 3.3% for R-ISS III vs. I; 6.3% vs. 2.8% for ISS III vs. I). The median rwPFS in HR patients were shorter than the lower risk subgroups (R-ISS III: 8.8 months [95% CI 7.1 - 11.0], R-ISS II: 12.1 months [95% CI 10.7 - 13.6], R-ISS I: 23.5 months [95% CI 13.8 - .]; ISS III: 10.4 months [95% CI 8.5 - 11.5], ISS II: 12.7 months [95% CI 10.7 - 14.3], ISS I: 16 months [95% CI 12.2 - 19.5]; HRCA: 10.1 months [95% CI 8.8 - 12.1], SRCA: 13.1 months [95% CI 11.3 - 14.8]). The 2-year rwOS was lower in the HR subgroups (R-ISS III: 0.65 [95% CI 0.59 - 0.70], R-ISS II: 0.79 [95% CI 0.76 - 0.81], R-ISS I: 0.91 [95% CI 0.85 - 0.95]; ISS III: 0.68 [95% CI 0.64 - 0.72], ISS II: 0.81 [95% CI 0.77 - 0.84], ISS I: 0.89 [95% CI 0.85 - 0.92]; HRCA: 0.75 [95% CI 0.71 - 0.79], SRCA: 0.79 [95% CI 0.76 - 0.81]). Discussion: This study found that median rwPFS and 2-year rwOS proportions were consistently lower among HR patients compared to the standard risk individuals. The majority of the HR patients were older, with decreased levels of physical functioning and worse indicators of end-organ damage including renal function, anemia, and hypercalcemia. Most patients received triplets with frequent use of PIs likely for aggressive disease control among HR patients. Some HR patients received more quads than lower risk patients suggesting treatment intensification, but HR patients also received stem cell transplants at a lower rate. Although a smaller proportion of patients have all the data collected needed for R-ISS classification, the consistent findings across treatment outcomes suggest that R-ISS is implementable in real world studies and has a greater discriminatory ability than ISS or HRCA alone. Overall, this study suggests that HR patients have relatively poor outcomes which calls for the study of risk-adapted implementation of novel therapies among this patient population in the US community practice settings. Figure 1 Figure 1. Disclosures Rahman: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company. Kim: Amgen: Current Employment, Current equity holder in publicly-traded company. Mateus: Amgen Inc.: Current Employment, Other: Work at Amgen as a contract employee through DOCS. Keegan: Amgen Inc.: Current Employment, Current holder of stock options in a privately-held company.

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