Shifting Treatment Patterns and Clinical Outcomes in Veterans Diagnosed with Waldenstrom Macroglobulinemia from 2006 to 2018

Background Waldenström's Macroglobulinemia (WM) is a rare indolent lymphoma with an estimated 1,500 new cases diagnosed each year in the United States (US). Over the last decade, several treatments have been introduced into the WM therapeutics landscape including, bendamustine, bortezomib, and most recently oral Bruton's kinase inhibitor (ibrutinib). There is limited information in the adoption of these WM treatments in real-world clinical settings in the US. We describe the practice patterns and clinical outcomes of first-line (1L) treatment of WM in a nationwide cohort of Veterans. Methods Using Veteran Affairs electronic health records (EHR) data, we identified Veterans who were diagnosed and received 1L treatment for WM between January 2006 and December 2018 in the Veterans Health Administration (VHA). Human annotation of EHR clinical records confirmed the diagnosis and 1L treatment regimens. Patients with another cancer diagnosis or patients with documentation that 1L treatment was received outside the VHA were excluded. Eligible patients were followed until loss to follow-up, death, or the end of the study period (June 30, 2019). Patient demographics, disease characteristics, and treatment patterns were identified. Local polynomial regression model curves were generated to demonstrate treatment changes over time. Unadjusted progression-free survival (PFS) and the unadjusted overall survival (OS) are also provided. Results We identified 505 patients diagnosed with WM in VHA between January 2006 thru December 2018. Of these, 318 patients received 1L treatment, with a median time from diagnosis to 1L treatment of 1.2 months (95% confidence interval [CI]: 0.5-5 months). The median age of WM patients was 69.9 years (standard deviation [SD]: 9.4 years), with approximately 73% of WM patients ≥65 years old. Prior to 1L treatment, the median hemoglobin and platelets observed were similar across all treatment groups, regardless of first 1L treatment. However, the median immunoglobulin M (IgM) was substantially lower in patient's treated with ibrutinib (2,570 mg/dL [range: 422-9,001 mg/dL]) and single-agent rituximab (R), 2,855 mg/dL (range: 84-7,880 mg/dL) when compared to those treated with chlorambucil +/- rituximab (4,416 mg/dL [range: (9-8,130 mg/dL]) and bortezomib/dexamethasone +/- rituximab (BDR), 4,086 mg/dL (range: 16-9,944 mg/dL). MYD88 testing occurred in 40 (13%) of patients, with testing most frequently occurring in patients treated with bendamustine +/- rituximab (BR), ibrutinib, and BDR- likely reflecting increased adoption in later periods. Hepatitis C testing occurred in 61 (19%) of patients, with testing most frequently occurring in patients treated with dexamethasone, rituximab, and cyclophosphamide (DRC), BDR, and BR. Over the study observation period, 1L practice patterns shift significantly with increased adoption of BR, BDR and ibrutinib and de-adoption of chemotherapy (Figure 1). The median follow-up time for all patients was 44 months (range: 1-147 months), although a shorter median follow-up time was observed in patients treated with therapeutics in recent years, such as ibrutinib (18 months [range: 2-53 months]) and BR (23 months [range: 4-86 months]). The median unadjusted PFS for all WM patients was 44 months (95% CI: 37-58 months) and the median unadjusted overall survival (OS) was 94 months (95% CI: 82-117 months). Conclusions The introduction of numerous therapeutic options throughout the past decade has profoundly altered the treatment landscape for WM, suggesting a shift in 1L practices from chlorambucil to BDR, BR, and most recently ibrutinib which has been increasingly adopted, since its approval in 2015, especially in older patients, suggesting that it may provide an effective therapeutic option for patients who may not be able to tolerate more aggressive treatment regimens. Limitations of this study include the differences observed in follow-up time as well as the limited number of patients in some 1L treatment groups. Further research is required to establish the long-term benefits and potential treatment-related toxicities of WM treatments in real-world clinical settings. Disclosures Sauer: Roche: Research Funding; Genentech, Inc.: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding. Halwani:AbbVie: Research Funding; Takeda: Research Funding; Roche: Research Funding; Genentech, Inc.: Research Funding; Miragen: Research Funding; Immunedesign: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Amgen: Research Funding; Pharmacyclics: Research Funding; Bristol Myers Squibb: Research Funding.

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Real-World Treatment Patterns Among a Contemporary Cohort of Commercially Insured Mantle Cell Lymphoma Patients in the United States

Blood ◽

10.1182/blood-2018-99-112532 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4845-4845

Author(s):

Lindsey E. Roeker ◽

Shaum Kabadi ◽

Chakkarin Burudpakdee ◽

Aimee Near ◽

Keiko Wada ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Research Funding ◽

Index Date ◽

Treatment Patterns ◽

Treatment Regimens ◽

Oral Medications ◽

Mantle Cell ◽

Insured Patients

Abstract Introduction Mantle cell lymphoma (MCL) is a rare, aggressive non-Hodgkin lymphoma associated with a poor prognosis. The approval of ibrutinib in November 2013 has changed the treatment paradigm for patients with relapsed or refractory MCL. There remains a lack of information on the current treatment patterns used in clinical practice in a contemporary cohort of commercially insured patients. We aimed to identify the treatment patterns for MCL overall and by line of therapy (LOT) and to describe patient demographics and clinical characteristics in a large cohort of commercially insured MCL patients. Methods A retrospective cohort study was conducted with the IQVIA Real-World Data Adjudicated Claims-US database. Adult patients (≥18 years old) with ≥1 claim for a NCCN-recommended MCL treatment between November 1, 2013 and December 31, 2017 were identified. Index date was the first treatment claim. Patients were also required to have ≥1 diagnosis of MCL during the study period (November 1, 2012 to January 31, 2018), ≥12 months of continuous enrollment prior to index date (pre-index period) and ≥30 days after index date (follow-up period). Patients were excluded if they were ≥65 years at index and not enrolled in Medicare Risk or Medicare Cost, enrolled in a clinical trial during the study period, had evidence of MCL treatment in the pre-index period (except for patients indexed on ibrutinib as it is indicated for MCL patients with ≥1 prior treatment), or had evidence of stem cell transplant (SCT) before index date. The most commonly observed MCL treatment regimens were identified, and demographic and clinical characteristics of patients and treatment durations by regimen were described. Treatment regimen was defined as the combination of all agents observed in the 35-day period after the first MCL treatment claim; treatment duration was defined as the start of treatment until a gap of ≥90 days between end date and next date of treatment or treatment modification. Treatment end date occurred 90 days after the end of the supply for oral medications or 30 days after the last administration for non-oral medications. Results There were 1,785 patients treated with the most commonly observed MCL treatment regimens. The most common regimens, irrespective of LOT, were rituximab monotherapy (including maintenance therapy; n=773, 43.3%), R-CHOP (n=723, 40.5%), B-R (n=436, 24.4%), and ibrutinib monotherapy (n=199, 11.1%). Overall, patients had a median (IQR) age of 57 (52-62) years, and 59.4% were male. Most patients were commercially or self- insured (57.5% and 33.6%, respectively). Patients had a median Charlson Comorbidity Index (CCI) of 0 (IQR 0-1; mean [SD] 0.9 [1.4]), with the most common CCI components being diabetes (15.7%), chronic pulmonary disease (12.8%), and congestive heart failure (9.5%). During the follow-up period (median [IQR] 22.5 [10.5-35.3] months), in addition to the MCL regimen(s), patients received radiation therapy (17.4%), SCT (10.0%), and/or immunotherapy (0.2%). The use of targeted therapies (i.e. lenalidomide, bortezomib) other than ibrutinib was infrequent. When considering treatment lines, R-CHOP was the most commonly observed first regimen, followed by rituximab, B-R, and ibrutinib; for the second and third observed regimens, rituximab was the most common, followed by ibrutinib (Figure 1). The median (IQR) duration for the first observed regimen was 8.1 (3.9-18.0) months for ibrutinib, 5.0 (3.3-5.6) months for B-R, 4.0 (2.5-4.4) months for R-CHOP, and 1.9 (1.7-4.4) months for rituximab; ibrutinib also had the longest duration in the second and third line (median [IQR] 5.5 [2.4-13.5] months and 8.3 [3.9-12.4] months, respectively). Conclusion This is the largest study of MCL patients describing treatment patterns in current clinical practice among commercially insured patients. MCL patients were most commonly treated with chemoimmunotherapy for all treatment lines while ibrutinib was the second most common LOT2 and LOT3 regimen. As the treatment landscape and clinical practice continues to change with the use of novel agents, future studies are warranted to further study toxicities and outcomes in the real-world setting. Disclosures Kabadi: AstraZeneca: Employment. Burudpakdee:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Near:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Wada:IQVIA received funds from AstraZeneca to conduct the analysis, interpret data, and coauthor the publication.: Consultancy. Mato:TG Therapeutics: Research Funding; Sunesis: Honoraria, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Prime Oncology: Speakers Bureau; Abbvie: Consultancy.

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Single-Agent Ibrutinib Vs Standard of Care for Patients with Relapsed/Refractory (R/R) and Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): An Adjusted Comparison of RESONATETM and RESONATE-2TM with the French Lyon-Sud Database

Blood ◽

10.1182/blood.v128.22.2039.2039 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2039-2039

Author(s):

Gilles A. Salles ◽

Lucile Baseggio ◽

Emmanuel Bachy ◽

Clementine Sarkozy ◽

Herve Ghesquieres ◽

...

Keyword(s):

Real World ◽

Research Funding ◽

Disease Stage ◽

Treatment Regimens ◽

Real World Setting ◽

Level Data ◽

Advanced Disease Stage ◽

Independent Risk Factors ◽

Male Sex

Abstract INTRODUCTION: The benefits of ibrutinib (ibr) have been demonstrated by the phase 3 RESONATE and RESONATE-2 trials for patients (pts) with R/R and TN (≥ 65 years) CLL, respectively. In these studies, ibr showed significantly improved progression-free survival (PFS) and overall survival (OS) vs approved comparators (ofatumumab [ofa] in RESONATE and chlorambucil [clb] in RESONATE-2). However, a number of other treatment regimens are widely used in clinical practice for CLL based on individual patient and disease characteristics; it is currently unknown if ibr results in better survival outcomes when compared directly with each of these other treatments. AIM: In the absence of a head-to-head comparison, we investigated the relative efficacy of ibr vs physician's choice (PC) in pts with R/R or TN CLL by comparing pt-level data from RESONATE and RESONATE-2 with data from pts in a real-world setting (the Lyon-Sud database). This database holds electronic medical records for 390 pts with CLL from the academic Lyon-Sud Hospital in France; nearly all patients were diagnosed between 1990 and 2014. This is the first analysis of ibr vs PC in a real-world setting for pts with TN CLL. METHODS: Pt-level data from RESONATE (ibr, n = 195; ofa, n = 196) were compared with data on pts with CLL from Lyon-Sud who received 2nd(n = 107) or later-line treatment (3rd [n = 62], 4th [n = 43], and subsequent [n = 51] lines). Similarly, RESONATE-2 (ibr, n = 136; clb, n = 133) pt-level data were compared with those of pts aged ≥ 65 years who received 1st-line treatment (n = 131). In order to account for non-comparability due to lack of randomization, a multivariate Cox proportional hazards model was used to compare PFS and OS between treatments, including line of therapy, age, sex, disease stage (based on Binet/Rai), and deletion 17p or 11q mutations as covariates. For the definition of PFS, missing data for date of disease progression for pts in Lyon-Sud who initiated subsequent therapy were replaced by the conservative proxy of date of initiation of next treatment. Predicted PFS and OS curves for the Lyon-Sud cohort were derived from the multivariate model. RESULTS: For R/R pts in Lyon-Sud, across all treatment lines the most frequent regimens used were rituximab (R) + chemotherapy (n = 46), bendamustine + R (BR; n = 28), fludarabine + cyclophosphamide + R (FCR) (n = 27), clb + R (n = 19), R monotherapy (n = 21), and R-CHOP-based (n = 19); the remaining percentages comprised various other therapies, each used in < 5% of pts. Median age at treatment initiation for Lyon-Sud and RESONATE was 69 and 67 years, respectively; median number of prior therapies was 2 and 3, and median follow-up was 30.0 and 21.9 months. More lines of prior therapy, older age, male sex, advanced disease stage (Binet C/Rai III/IV), and presence of deletion 17p/11q were independent risk factors for worse PFS and OS outcome. After adjustment for differences in baseline characteristics, PFS and OS hazard ratios (HRs) for ibr vs PC were 0.18 (95% confidence interval [CI], 0.13-0.26) and 0.28 (0.17-0.46), respectively. Adjusted HRs for ibr vs the most frequent treatments ranged from 0.09 (R monotherapy) to 0.38 (FCR) for PFS and 0.21 (R monotherapy) to 0.33 (FCR) for OS; all were statistically significant. For TN pts in Lyon-Sud, the most frequent treatment regimens used were FCR (n = 40), clb + R (n = 21), clb monotherapy (n = 17), R-(mini)CHOP (n = 11), and BR (n = 11). Median age at treatment initiation was 73 years for both Lyon-Sud and RESONATE-2; median follow-up was 36.9 and 28.1 months, respectively. Older age, male sex, and advanced disease stage were independent risk factors for worse PFS and OS outcome. After adjustment for baseline differences, the PFS and OS HRs for ibr vs PC were 0.25 (0.14-0.47) and 0.41 (0.17-0.99). Predicted PFS and OS curves for both R/R and TN patients are presented in Figure 1. CONCLUSIONS: Investigation of survival outcomes suggests that ibr administered to pts in RESONATE and RESONATE-2 was more effective than PC used in a real-world cohort of French pts with R/R or TN CLL, suggesting a 4.8-fold improvement in PFS and a 3.4-fold improvement in OS in R/R pts and 4-fold and 2.4-fold improvements in TN pts, respectively. These results further support the growing evidence that ibr significantly improves both PFS and OS vs commonly used regimens in the R/R and TN settings, and could have important implications for improving treatment of CLL in clinical practice. Disclosures Salles: Janssen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding. Sarkozy:Sandoz: Research Funding; Janssen Research & Development: Honoraria; Gilead: Honoraria; Takeda: Research Funding. Ghesquieres:Mundipharma: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche France: Research Funding. Diels:Johnson & Johnson: Employment, Equity Ownership. Besson:Janssen: Employment. MacDougall:Janssen Research & Development: Research Funding; IMS Health: Employment. Hermans:Janssen Research & Development: Research Funding; IMS Health: Employment. Healy:Janssen Research & Development: Employment. Garside:Janssen Research & Development: Employment. Iraqi:Janssen Research & Development: Employment.

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Real-World Outcomes for Standard-of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2021-146250 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4075-4075

Author(s):

Michel Delforge ◽

Marie-Christiane Vekemans ◽

Sébastien Anguille ◽

Julien Depaus ◽

Nathalie Meuleman ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Retrospective Chart Review ◽

Standard Of Care ◽

Real World Data ◽

Advisory Committees ◽

Treatment Regimens

Abstract Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p<0.001), being male (p=0.001), older age (p<0.001), shorter duration of prior lines (p<0.001), shorter time to progression in prior line (p=0.025), and higher LDH levels (p<0.002) were prognostic for worse outcomes for both OS (Figure 1) and PFS. Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of <10 months. A wide variety of treatment regimens used in clinical practice confirm the absence of a clear standard-of-care in this patient population. The literature also confirms that these poor outcomes observed in Belgium, for this subset of MM patients, are similar in other countries. These real-world data highlight the high unmet medical need in this patient population and critical need for new and effective treatment options. MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

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Treatment patterns and overall survival in HER2+ metastatic breast cancer at US community oncology practices

Future Oncology ◽

10.2217/fon-2021-0405 ◽

2021 ◽

Author(s):

Gregory A Vidal ◽

Santosh Gautam ◽

Anna Vlahiotis ◽

Maxine D Fisher ◽

Sonia Pulgar ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Real World ◽

Metastatic Breast ◽

Standard Of Care ◽

Treatment Patterns ◽

Adult Women ◽

Community Oncology

Aim: To describe real-world treatment patterns/outcomes among patients with HER2+ metastatic breast cancer (MBC). Materials & methods: Real-world treatments and overall survival (OS) were evaluated among adult women diagnosed with HER2+ MBC, with and without brain metastases (BMs), between June 1, 2012 and May 31, 2018 using electronic medical records from the Definitive Oncology Dataset. Results: Among 372 patients, 69% initiated first-line trastuzumab plus pertuzumab-based therapy; many therapy combinations were utilized in the second- to fourth-line. During follow-up (median 24.8 months), 18% of patients died (22% with and 16% without BMs). Mean OS was shortest among patients with BMs at MBC diagnosis in the third- and fourth-line. Conclusion: OS was poor, and no clear standard of care was observed among patients with HER2+ MBC progressing on trastuzumab-based therapies.

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Real-world treatment patterns and overall survival in previously treated advanced renal cell carcinoma patients receiving nivolumab in the UK.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16561 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16561-e16561

Author(s):

Tom Waddell ◽

Kate Fife ◽

Richard Griffiths ◽

Anand Sharma ◽

Poonam Dhokia ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Real World ◽

Renal Cell ◽

Treatment Patterns ◽

Case Report Form ◽

Real World Evidence ◽

Previously Treated

e16561 Background: CheckMate 025 demonstrated favorable efficacy and safety results for nivolumab monotherapy in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, real-world evidence on treatment patterns and clinical outcomes is limited. Methods: This multi-centre, retrospective cohort study examined treatment patterns and overall survival (OS) in aRCC patients treated with nivolumab monotherapy. Eligible patients who initiated nivolumab at second-line (2L) or beyond (index) between 01 March 2016 and 30 June 2018 were sampled from four UK centers. Data were extracted using an electronic case report form from index to earliest of: most recent visit; death; end of follow up (31 May 2019). Results: Overall , 151 patients were included in analyses (mean age at index 66.9 years, 72.2% male, median follow-up from index 15.2 months), with 109 (72.2%) and 42 (27.8%) receiving nivolumab at 2L and ≥ third-line (3L+), respectively. Key clinical characteristics are outlined in Table 1. All 2L nivolumab patients had received first-line (1L) tyrosine kinase inhibitors (TKI), pazopanib (57.8%), sunitinib (30.3%), or both in sequence (10.1%). After 2L nivolumab, 3L cabozantinib (36/52, 69.2%) was most common. Most 3L nivolumab patients received 2L TKI (31/36, 86.1%) - commonly axitinib (70.9%). After 3L nivolumab, most patients received fourth-line cabozantinib (8/12, 66.7%). Median time on line of therapy (LOT) decreased with LOT progression: from 7.8 months at 1L to 4.6 months at fifth-line (5L). The proportion of patients who discontinued treatment due to adverse events decreased by LOT, (28.6%, 22.7%, 16.0% and 0%, and 34.7%, 28.1%, 0% and 0% from 2L to 5L, overall and for nivolumab treatment, respectively). Overall, median OS from nivolumab initiation was 19.2 months [95% CI, 16.9-27.0]. Patients who received 2L nivolumab had longest median OS (23.0 months [95% CI, 17.2, not reached]), comparable to CheckMate 025 (25.8 months [95% CI, 22.2-29.8]). Median OS for 3L+ nivolumab patients was 12.4 months [95% CI, 8.8, 23.2]. Among 2L nivolumab patients, 73.9%, 46.2%, and 33.6% survived 12, 24, and 36 months, respectively. For the same respective timeframes, 52.4%, 24.7%, and 18.6% of 3L+ nivolumab patients survived. Conclusions: This study provides real-world evidence on the characteristics, treatment patterns and effectiveness of 2L or ≥ 3L nivolumab monotherapy in previously treated aRCC patients. OS results from UK routine clinical care were comparable to those found in CheckMate 025.[Table: see text]

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220 Real-world outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0220 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A239-A239

Author(s):

Wolfram Samlowski ◽

Robert Nicholas ◽

Tayla Poretta ◽

Andriy Moshyk ◽

Jonathan Rajkumar ◽

...

Keyword(s):

Overall Survival ◽

Real World ◽

Treatment Patterns ◽

Stage Iii ◽

List Type ◽

Stage Iiia ◽

American Joint Committee ◽

The Us ◽

Resected Stage

BackgroundNivolumab is approved in the US and EU for the adjuvant treatment of resected stage III-IV melanoma based on results from the CheckMate-238 clinical trial.1,2 However, the trial did not enroll any patients with Stage IIIA disease per the American Joint Committee on Cancer (AJCC) 7th edition criteria and included a limited number of patients with stage IIIA disease per the AJCC 8th edition.3,4,5Recognizing the need for real-world data to assess outcomes of patients with resected stage IIIA melanoma treated with adjuvant nivolumab, a non-interventional study was conducted to investigate treatment patterns and outcomes among patients receiving adjuvant nivolumab within the US community practice setting.MethodsA retrospective analysis of the US Oncology Network’s iKnowMed medical data was conducted to examine patients with resected stage IIIA melanoma treated with adjuvant nivolumab between 01-Jan-2018 and 31-Dec-2019 with a follow-up period through 31-Mar-2020. Patients were followed for up to 27 months after their sentinel lymph node biopsy. Baseline demographic/clinical characteristics and treatment patterns were examined descriptively. Duration of treatment (DOT) and overall survival were analyzed using the Kaplan-Meier method.ResultsA total of 58 patients with stage IIIA melanoma treated with adjuvant nivolumab were identified. Median age was 57.8 years (range 21.5–93.5), 62.1% were male, and 75.9% were Caucasian. Among patients with a documented Eastern Cooperative Oncology Group (ECOG) performance status (51.7%), all had an ECOG score of 0 or 1. Median follow-up time was 12.6 months (range 0.3–25.1). Median DOT was 10.6 months (range 6.8–12.0). Overall survival rates at 12 and 24 months were 97.7% (95% CI 84.6–99.7) and 92.2% (95% CI 69.6–98.2), respectively.ConclusionsThis real-world analysis of patients with stage IIIA melanoma treated with adjuvant nivolumab showed that a large proportion of patients were alive at the end of the study period, suggesting these patients have a favorable prognosis. Further investigation and follow-up is warranted to assess clinically relevant outcomes among patients with resected stage IIIA melanoma.Ethics ApprovalThe study was approved by US Oncology Inc’s Institutional Review Board, approval number 20-020E-2020-0224-01.ReferencesWeber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. NEJM 2017;377:1824–35.Weber J, Mandala M, Del Vecchio M, et al. Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: A randomized, double-blind, phase 3 trial (CheckMate 238). Ann Oncol 2017;28(5):632–33.Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27(36):6199–6206.Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017;67(6):472–492.National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Cutaneous Melanoma Version 3.2020 - May 18, 2020. 2020.

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Time to Development of Treatment-Emergent Extramedullary and Osseous Plasmacytomas in the Era of Novel Agents: An Analysis of Upfront Regimens in Newly Diagnosed MM Incorporating Lenalidomide and Bortezomib

Blood ◽

10.1182/blood.v124.21.3468.3468 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3468-3468

Author(s):

Cindy Varga ◽

Jacob P. Laubach ◽

Irene M. Ghobrial ◽

Matthew Weinstock ◽

Claudia E. Paba-Prada ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Research Funding ◽

Rapid Development ◽

Sensitivity Analyses ◽

Front Line ◽

Rank Tests ◽

Advisory Committees ◽

Treatment Groups

Abstract Introduction: The introduction of proteasome inhibitors (PI) and immunomodulatory derivatives (IMIDs) has been associated with substantial improvement in overall survival of patients with multiple myeloma (MM). In the era of novel agents, there have also been concerns of an increased incidence of extramedullary disease (EMD), and of a hypothetical risk that combined use of PIs and IMIDs for frontline treatment might select more rapidly for aggressive clones that could precipitate EMD. It is difficult to determine the true frequency of treatment-emergent EMD, as incidence rates may be influenced by the impact of specific therapies, as well as confounded by changes in overall survival, and the increased use of sensitive imaging modalities. Objective: The primary objective of our study was to evaluate whether the addition of lenalidomide (Len) to bortezomib (Bort)-based front-line regimens precipitated the more rapid development of treatment-emergent EMD, either in the form of extraosseous or osseous extramedullary plasmacytomas. Potential risk factors for and the prognostic impact of EMD development were also examined. Patients-Methods: We performed an IRB-approved retrospective comprehensive medical chart review of 117 MM patients enrolled in 8 clinical trials of first-line treatment with Bort-based regimens with Len (Bort-Len-Dexamethasone [known as RVD], its combination with cyclophosphamide [Cy], vorinostat or liposomal doxorubicin) or without Len (specifically, Bort monotherapy; MPV; CyBorDex; MPV-CNT0328). In these 2 treatment groups, the development of EMD was assessed in the form of extraosseous (soft-tissue mass distant from bone) or osseous (mass originating from cortical bone) plasmacytomas. The primary endpoint was time from diagnosis until development of plasmacytoma (osseous; extraosseous; or any of the 2), based on radiologic imaging, biopsy and/or physical examination, with censoring at last disease follow-up date for patients who did not develop EMD. We compared the rates of EMD in these 2 patient cohorts through sensitivity analyses at truncated follow-up times of 5- and 7-years, to control for any potential confounding effects of shorter follow-up in patients receiving combined Bort-based therapy with vs. without Len. Results: The median follow-up time from diagnosis was 6.1 years (range 0.1-10.2 years) for the entire cohort; and 5.6 years (range 1.5-7.4) vs. 8.9 (range 0.1-10.2), respectively, for Bort-based treatment with vs. without Len. Treatment-emergent EMD was observed in the form of osseous (n=32, 27.4%), extraosseous (n=19, 16.2%) or any osseous or extraosseous plasmacytoma (n=40, 34.2%). Stage III ISS or low Hb (<12 g/dL) at diagnosis was associated with shorter time to development of extraosseous plasmacytomas (univariate analyses, p=0.02, for both parameters). After development of extraosseous plasmacytomas, the median OS was 0.9 years (range 0.1-4.8 years). In sensitivity analyses with follow-up times truncated at 5 years (rates of EMD and 95% CI summarized in Table 1) or 7 years (data not shown), the rates of any form of EMD showed no statistically significant difference between the 2 treatment groups (log-rank tests p>0.1 for all comparisons). Conclusion: Based on these results, there is no evidence to suggest that combination Bort- Len-based front-line therapy precipitates more rapid development of EMD. Conversely, the development of extra osseous plasmacytoma was associated with poor OS regardless of prior treatment. Further confirmation with extended follow-up, as well as studies of treatment effect, correlatives (incorporating both genotypic and phenotypic features), and the incidence as well as outcome of EMD are warranted. Table 1: Sensitivity analyses (follow-up times truncated at 5 years) Bort-Len based treatment (N=69 patients) Bort-based treatment without Len (N=48 patients) P-value (Log-rank tests) Hazard ratio Osseous Plasmacytoma (%, 95% CI) 0.5428 0.78(0.36,1.73) At 2 years 7 (3-7) 11 (5,25) At 4 years 17 (10,29) 25 (14,41) At 5 years 24 (15,38) 27 (16,44) Total cases 14 11 Extraosseous Plasmacytoma (%, 95% CI) 0.1691 0.51(0.19,1.36) At 2 years 4(1,13) 5(1,17) At 4 years 8(3,18) 15(7,30) At 6 years 12(6,25) 23(13,40) Total cases 7 9 Any Osseous or Extraosseous Plasmacytoma (%, 95% CI) 0.4236 0.76(0.38,1.50) At 2 years 10(5,20) 16(8,30) At 4 years 24(15,36) 29(17,45) At 6 years 30(20,44) 37(24,53) Total cases 18 15 Disclosures Laubach: Novartis: Research Funding; Onyx Pharmaceuticals: Research Funding. Ghobrial:Millennium/Takeda: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Mitsiades:Millennium Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen : Research Funding; Johnson & Johnson: Research Funding.

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Real-World Differences in Characteristics and Survival of Relapsed AML Patients with and without Transplant

Blood ◽

10.1182/blood-2018-99-118621 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2297-2297

Author(s):

Abdalla Aly ◽

Saurabh Ray ◽

Anuj Shah ◽

Marc Botteman

Keyword(s):

Overall Survival ◽

Real World ◽

Research Funding ◽

Cell Transplant ◽

Employment Equity ◽

Risk Of Death ◽

Hazard Ratios ◽

Equity Ownership ◽

To Receive

Abstract Background: Some AML patients, particularly those relapsing rapidly, may not get a chance to receive a potentially curative stem cell transplant (SCT) due to early death, among other reasons. This study compares the differences in characteristics and survival of relapsed AML patients with and without SCT, as observed in a real-world setting. Methods: Relapsed AML patients aged 66-75 years were identified from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database by medical claims associated with ICD-9 code 205.02 (2009-2014). Patients were followed from relapse to the earliest of death, SCT, or end of follow-up. Baseline characteristics were compared between relapsed AML patients with and without SCT. The SCT rates were estimated after adjusting for the competing risk of death. The Fine and Gray method was used to identify predictors of receiving SCT and were reported in terms of sub-distribution hazard ratios (SHR) and 95% confidence intervals (CI). Kaplan-Meier estimates (reported in terms of median and 6-, 12-, and 24-months survival rates, tested with a log Rank test statistic) and a Cox proportional hazards model adjusting for age, sex, race, Census region, marital status, urban location, Charlson comorbidity index (CCI), and diagnosis year (reported in terms of hazard ratios (HR) and 95% CI) was used to assess the difference in survival between patients with and without SCT. Results: Of the 474 relapsed AML patients (median age, 70 years, median follow up, 4.4 months, male, 55%) included in the study, 8% received SCT, 80% died without having SCT and 12% were administratively censored. Patients were less likely to receive SCT if they were 71-75 years old (SHR 0.28, 95% CI (0.19 to 0.41; P <.001) and had higher comorbidity with CCI >3 (SHR 0.16, 95% CI (0.06 to 0.44; P <.001). The median overall survival was 16.1 months for patients with SCT vs. 4.1 months for those without SCT (log rank P <.001; adjusted HR 0.52, 95% CI (047 - 0.57; P <.001)). The 6-, 12-, and 24-month overall survival for all relapsed AML patients was 42%, 26%, and 12%, respectively. For patients with SCT, the 6-, 12-, and 24-month overall survival was 84%, 59%, and 43%, respectively. For patients without SCT, the 6-, 12-, and 24-month overall survival was 39%, 23%, and 12%, respectively. Conclusions: Relapsed AML patients who received SCT experienced significantly longer survival compared to those who did not receive SCT in this elderly study population. However, only 8% of all relapsed AML patients received SCT. Therapies that bridge more patients to SCT are expected to improve overall survival in this high unmet need population. Disclosures Aly: AstraZeneca: Research Funding; Celgene: Research Funding; BMS: Research Funding; Pharmerit International: Employment, Research Funding; Daiichi Sankyo Incorporated: Research Funding. Ray:Daiichi Sankyo Incorporated: Employment, Equity Ownership. Shah:Celgene: Research Funding; Pharmerit International: Employment, Research Funding; Daiichi Sankyo Incorporated: Research Funding; BMS: Research Funding. Botteman:Daiichi Sankyo Incorporated: Research Funding; BMS: Research Funding; Celgene: Research Funding; Pharmerit International: Employment, Equity Ownership, Research Funding; Bioverativ: Consultancy, Other: Provided consulting to Bioverativ, Research Funding.

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Health Economic Burden and Treatment-Based Survival for Current Follicular Lymphoma Treatment Practice in Japan Using a Nationwide Retrospective Claims Database

Blood ◽

10.1182/blood-2019-122639 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2129-2129

Author(s):

Saaya Tsutsue ◽

Kensei Tobinai ◽

Jingbo Yi ◽

Bruce Crawford

Keyword(s):

Treatment Group ◽

Research Funding ◽

Index Date ◽

Survival Rates ◽

Treatment Patterns ◽

High Survival ◽

Inclusion Criteria ◽

Treatment Regimens ◽

Index Treatment

ABSTRACT Introduction: Follicular lymphoma (FL) is an indolent form of non-Hodgkin lymphoma (NHL), which accounts for 20-30% of all NHL cases. In most patients, FL is diagnosed in advance stages, mild disease progression and long treatment period that may incur a great burden to patients and healthcare system. However, to our knowledge there is no comprehensive analysis which have been done in the real world setting in Japan. Therefore, we conducted a retrospective claim database study to elucidate the lines of treatment patterns as well as the associated healthcare resource utilization (HCRU), and 3- and 5-year overall survival (OS) among 3,593 Japanese patients with a median age of 65.0 years. Methods: This retrospective study analyzed data from the Medical Data Vision (MDV) database for patients diagnosed with FL (ICD-10: C82). The MDV database is an electronic health records-based database comprised of anonymized inpatient and outpatient data covering over 25 million patients and over 374 Japanese hospitals, approximately 22% of acute phase hospitals, including 187 cancer therapeutic facilities. Patients who received treatment during the identification period from 1 October 2008 to 31 December 2017 were selected. Patients were required to have data for at least 6 months before the first treatment date (ie, patient index date) and at least 12 months after the index date (unless they died). Costs were converted from Japanese yen to US dollars using the exchange rate based on January of each year of service. For 3- and 5-year OS, patients who had a record of death in their hospital discharge were counted as an event, otherwise they were censored at the latest of: end of patient record, end of data availability, or end of the 3- or 5- year period. Results: A total of 3,593 patients with FL met the inclusion criteria of which 51.2% was female patients. Of these 3,593 patients who met the inclusion criteria, 3,004 patients (83.6%) received rituximab-based (R) therapy as index treatment, of which 1309 (36.4%) of patients received R-CHOP. During the subsequent lines of therapies, patients received heterogeneous treatment regimens (fig 1). Overall, the average healthcare cost during follow-up period was $67,557.40 for all FL patients, ranging from $39,340 (immunotherapy, targeted therapy, or hormone therapy without R) to $ 95,095 (other R-based chemotherapy). The average number of outpatient visits during follow-up for all FL patients was 51, ranging from 44.6 to 55.1 for each treatment group. There were 3,394 (94.5%) patients who had at least one hospitalization during follow up period. Among those who had at least one hospitalization, the average number of hospitalizations was 3.8 for all FL patients, ranging from 2.5 to 4.6 for each treatment group. The average number of days of hospitalization during follow-up was 74.5 for all FL patients, ranging from 31 to 110.4 for each treatment group. 85 (2.4%) FL patients received a stem cell transplant (SCT) during follow-up at the age under 79 years, with other R-based therapies having the highest percentage (7.6%). There were 346 (9.7%) FL patients receiving radiation therapy, ranging from 8.1% (other treatment groups) to 24.1% (immunotherapy, targeted therapy, or hormone therapy without R). There were 337 deaths (9.4%) recorded within 3 years and 400 (11.1%) within 5 years of index treatment. The median Kaplan-Meier OS was not reached for most analysis groups due to the overall high survival rates. When comparing overall survival by index regimen group, chemotherapy without R consistently had worse survival, especially compared to R-based regimens (fig. 2). Conclusions: Patients with FL in Japan received diverse treatment regimens and multiple lines of therapy with relatively high survival rates. Majority of patients have received R-based therapies and have shown longer survival rates compared to those who have received chemotherapy without R. This is the first study to clarify lines of treatment patterns using retrospective claims database and treatment group-based OS in FL patients in Japan, which will give clinical insights of the landscape of daily practices and the associated real world health economic burden for patients, clinicians and healthcare providers to support their better decision makings. Disclosures Tsutsue: Celgene: Employment. Tobinai:Solasia: Honoraria; Mundi Pharma: Consultancy, Honoraria, Research Funding; Takeda Pharmaceutical: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Ono Pharmaceutical: Consultancy, Honoraria, Research Funding; Yakult: Honoraria; AbbVie: Research Funding; Meiji Seika: Honoraria; Janssen Pharmaceutical: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; HUYA Bioscience: Consultancy, Honoraria; Zenyaku Kogyo: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Eisai: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Verastem: Honoraria; Kyowa Kirin: Honoraria, Research Funding. Yi:Celgene: Consultancy. Crawford:Celgene: Consultancy.

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The Relationship between Age and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in a Cohort of Older Patients with Acute Myeloid Leukemia (AML)

Blood ◽

10.1182/blood-2018-99-111274 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3588-3588

Author(s):

Bruno C. Medeiros ◽

Sacha Satram-Hoang ◽

Faiyaz Momin ◽

Monika Parisi

Keyword(s):

Overall Survival ◽

Mortality Risk ◽

Real World ◽

Survival Benefit ◽

Older Patients ◽

Research Funding ◽

Comorbidity Score ◽

Comorbidity Burden ◽

Medicare Database

Abstract Introduction: The use of allogeneic HSCT is considered a potential cure for AML but its use is limited in older patients because of significant comorbidities and increased transplant-related morbidity and mortality. However, there is evidence to suggest that older patients up to 80 years old may tolerate and benefit from intensive treatment, despite deteriorating organ function. This real-world analysis compared outcomes of Medicare-aged, chemotherapy-treated AML patients with or without HSCT. Methods: We performed a retrospective cohort analysis of 4,772 patients with a first primary AML in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 and December 31, 2013, were aged > 66 years, continuously enrolled in Medicare Part A and B with no health maintenance organization (HMO) coverage in the year prior to diagnosis, and had received chemotherapy treatment within 3 months of diagnosis. Demographic and clinical characteristics were compared between patients who received HSCT and those who did not, using chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables. Unadjusted Kaplan-Meier survival plots were used to assess overall survival. Cox proportional hazards regression modeling evaluated the independent effects of covariates on overall survival, including receipt of HSCT, age, sex, race, prior myelodysplastic syndromes (MDS), poor performance indicators (PPIs), comorbidity burden, income, education, marital status, year of diagnosis, and geographic region. Date of last follow-up was December 31, 2015, permitting a minimum 2-year follow-up. Results: Of 4,772 patients with a first primary AML in the linked SEER-Medicare database, 403 (8%) underwent HSCT therapy after chemotherapy and 4,369 (92%) did not. Rates of HSCT increased over the study time period from 7% in 2000 to 12% in 2012 (P = 0.0033). Of the 403 patients who underwent HSCT, the majority (82%) were aged ≤ 75 years. Overall, patients in the HSCT group were younger at diagnosis (71 vs 75 years), more likely to be male (63% vs 54%), be married (66% vs 60%), less likely to have high-risk disease (11% vs 15% with prior MDS) or PPIs (4% vs 8%), and had lower comorbidity burden (59% vs 53% with a comorbidity score of 0) versus patients treated with chemotherapy only. In a subset analysis stratified by age, the relationships observed between patient characteristics and HSCT receipt persisted in the younger cohort of patients (≤ 75 years) but not in the older cohort (> 75 years). The unadjusted median overall survival was higher for the HSCT group (14.2 months) versus the non-HSCT group (4.8 months; log-rank P < 0.0001). In multivariate survival analysis, patients who underwent HSCT had a 40% lower risk of death versus those who did not undergo HSCT (hazard ratio [HR] 0.60; 95% CI 0.53-0.67). Advanced age, male sex, higher comorbidity score, prior MDS, and PPIs were significantly associated with higher risk of mortality. Stratifying by age, the survival benefit with HSCT was only demonstrated in the younger cohort aged ≤ 75 years (HR 0.53; 95% CI 0.46-0.60); no difference in mortality risk was noted in the older cohort aged > 75 years (HR 0.85; 95% CI 0.67-1.08). Conclusions: Overall, only 8% of patients receiving antileukemic therapy underwent subsequent HSCT therapy, and 82% of patients who did undergo HSCT were aged ≤ 75 years. HSCT was associated with a 40% reduction in mortality risk versus patients receiving chemotherapy only, and the survival benefit was more pronounced among the younger cohort aged ≤ 75 years, with a 47% reduction in mortality risk. Chronologic age appears to be the driving factor in HSCT receipt and prognosis, and these findings provide important new information on real-world outcomes on the benefit of HSCT in an elderly population. Disclosures Satram-Hoang: Celgene Corp.: Research Funding; Genentech: Research Funding. Parisi:Celgene Corp.: Employment, Equity Ownership.

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