Insurance Is No Longer a Determinant to Improve Overall Survival for Patients Diagnosed with HL, DLBCL or PCNS in an Enriched Hispanic Community

Abstract Background Variables that determine overall survival (OS) in patients diagnosed with Hodgkin (HL) and Non-Hodgkin lymphomas (NHL) have been widely studied in the United States. Inequalities in survival has been noted when patients lack insurance (Cancer PMID: 26058564). However, healthcare disparities exist within the different cancer subtypes and ethnic minorities. In the case of Follicular lymphoma, uninsurance has been linked with worse outcomes (Blood PMC6137560). For Burkitt and plasmablastic lymphomas, insurance does not seem to have a repercussion in survival (Blood 136 Supplement 1:45-46) (Leuk Lymphoma PMC6923579). In subgroup analysis, Hispanics (HI) have been noted to have higher rate of uninsurance with no significant distinction in OS in patients with DLBCL (Blood136 Supplement 1: 9). There is a need to understand determinants in ethnic disparities in outcomes for HL and NHL. This is the first large statewide population-based study differentiating ethnicity, insurance status and survival for HL, diffuse large B cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNS) in Texas. Material and Methods A retrospective analysis of patients diagnosed with HL, DLBCL, PCNS recorded in the Texas Cancer Registry from 2006-2017 was carried out. Inclusion criteria was histopathologic proven HL, DLBCL, and PCNS. Patients were divided into HI and non-Hispanics (NH), and subsequently in insured (i) and uninsured (un), for a total of four cohorts for comparison: iHI, unHI, iNH and unNH. Survival time was measured using the day of diagnosis to last date of follow up or death. For each cohort, median survival (MS) and analysis at 2,5 and 10 years (y) was calculated. Survival distribution were determined based on Kaplan-Meier curves. Results From 2006-2017, 21,229 patients with HL, DLBCL, PCNS were diagnosed in Texas. Of these, 6,004 patients (iHI n=1,369, unHI n=376, iNH n=3,781, unNH n=478) were diagnosed with HL (Graph 1), 14,366 patients (iHI n=2,810, unHI n=635, iNH n=10,273, unNH n=648) were diagnosed with DLBCL (Graph 2) and 859 patients (iHI n=195, unHI n=54, iNH n=559, unNH n=51) were diagnosed with PCNS (Graph 3). MS was outstanding for uninsured compared to insured patients with HL, DLBCL and PCSN. In HL, MS for iHI was 9.8 y, unHI was not reached, iNH was 10.3 y, and unNH was 10.8 y. In DLBC, MS was 3.7 y, 9.3 y, 4.2 y and 5.3 y, respectively. In PCNS, MS for these groups corresponded to 0.9 y, 0.8 y, 0.7 y and 3.2 y. Survival probability at 2-,5- and 10y among i vs un was noteworthy in HL, DLBCL and PCNS (Table 1). In HL, iHI was 0.762, 0.686 and 0.448; unHI was 0.873, 0.784 and N/A; iNH was 0.843, 0.765 and 0.584, and unNH was 0.846, 0.782 and 0.703, respectively. In DLBCL, for iHI it was 0.573, 0.456 and 0.222; unHI was 0.685, 0.631 and 0.350; iNH was 0.602, 0.469 and 0.174; unNH was 0.583, 0.510 and 0.239, accordingly. In PCNS, for iHI it was 0.374, 0.219 and N/A; unHI was 0.314, 0.174 and N/A; iNH was 0.354, 0.229 and 0.061; unNH was 0.516, 0.473 and 0.473, correspondingly. Overall Survival (OS) was statistically significant for iHI vs unHI vs iNH vs unNH when comparing HL, DLBCL and PCNS, with p values of <0.0001, <0.0001 and 0.037, respectively (Graph1-3). In HL the group with the best OS was unHI. This was also evidenced for DLBCL. However, for PCNS this trend was noted in unNH. In both three malignancies, the highest OS rate was reported in uninsured population. Conclusions For HL, DLBCL and PCNS the uninsured population has statistically significant better OS at 10 y. Interestingly for HL and DLBCL this corresponded to unHI while for PCNS was unNH. This paroxysmal finding may be due to standardized treatment, immediate healthcare enrolling after diagnosis and/or different community healthcare practices. Additionally, this population may have unique behaviors such as higher rate of compliance/adherence, environmental exposures or genetic predisposition to improved survival. Nonetheless, lack of insurance may delay diagnosis, need for multiple lines of chemotherapies, increase the rate of metastatic disease or recurrences. Accordingly, as more expensive and personalized therapies evolve, insurance status can limit access to these treatment regimens. Therefore, although insurance is no longer a determinant for improving OS for patients diagnosed with HL, DLBCL or PCNS, it can have implications for other oncological outcomes. Figure 1 Figure 1. Disclosures Diaz Duque: Incyte: Consultancy; Morphosys: Speakers Bureau; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Consultancy; ADCT: Consultancy.

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The impact of ethnicity and insurance status on stage of cancer at diagnosis and overall survival of breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.154 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 154-154

Author(s):

M. Omaira ◽

M. Mozayen ◽

R. Mushtaq ◽

K. Katato

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

African Americans ◽

Private Insurance ◽

Ethnic Disparities ◽

The United States ◽

Insurance Status ◽

Advanced Stage ◽

Stage At Diagnosis ◽

The Impact

154 Background: Major advances in early diagnosis and treatment of breast cancer (BC) have been achieved with significant declines in mortality. However, not all segments of the United States population have experienced equal benefits from this progress. Though ethnic disparities in BC outcome have been attributed to lack of adequate health insurance, the differences in outcome when insurance and socioeconomic status are similar still exist. We elected to examine the effect of insurance status at diagnosis, and whether race is an independent risk of poor outcome in a population from a community-based cancer database. Methods: A retrospective study on BC among patients aged 18 to 64 years were identified, between 1993 and 2005, using data from the Tumor Registry at Hurley Medical Center in Flint, Michigan. Patient’s characteristics included age, race, stage at diagnosis, and primary payer. Insurance status was classified as uninsured/Medicaid, private insurance, and Medicare disability (Medicare under age 65). The 5-year overall survival (OS) was calculated, in respect to patient ethnicity, and compared between the three insurance groups using Fisher’s exact test. Results: A total of 779 patients have been identified with diagnosis of BC. 147 patients were excluded due to incomplete data. 632 patients were analyzed. African Americans were 228 (36%), Caucasians 391 (62%), and other ethnicities 13 (2%). Mean age at diagnosis was (49.21) for African Americans versus (51.35) for Caucasians (p = 0.002). African Americans were more likely to present at advanced stage (III, IV) than Caucasians (17% versus 10%, p = 0.017). However, this difference was not statistically significant when adjusting for insurance status. Although both ethnicities had similar OS in respect of their insurance group, patients with Medicaid/uninsured had significantly lower OS compared to patients with Medicare disability (p = 0.006) and private insurance (p < 0.0001) respectively. Conclusions: Uninsured/Medicaid patients with breast cancer have worse outcome when compared to patients with Medicare or private insurance. Ethnicity is not an independent risk factor of advanced stage at diagnosis and poorer outcome.

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Predictors of Central Nervous System (CNS) Involvement in North American Adult T-Cell Leukemia Lymphoma (ATLL) and Their Survival Pattern

Blood ◽

10.1182/blood-2021-151447 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1400-1400

Author(s):

Riya Patel ◽

Shafia Rahman ◽

Nishi Shah ◽

Astha Thakkar ◽

Ana Acuna-Villaorduna ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

North American ◽

Research Funding ◽

Bone Marrow Involvement ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

The United States ◽

Publicly Traded ◽

Cns Involvement

Abstract Introduction: North American-ATLL (NA-ATLL) is a distinct genomic and clinical entity when compared with Japanese ATLL. Despite the frequent CNS involvement by this entity there are no prognostication tools to identify variables associated with higher risk. We studied one of the largest NA-ATLL cohorts in the United States at a minority rich ethnically diverse New York City based tertiary care center to identify discrete variables that may be associated with CNS involvement. Additionally, we examined the predictive power of the previously validated International Prognostic Index (IPI) developed for Diffuse Large B-cell Lymphoma (DLBCL) in terms of CNS involvement as well as overall survival in our cohort. In our previous work, we assigned CNS involvement of ATLL if: 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive; 2) CNS imaging was positive for disease involvement or 3) physical exam was compatible with neurologic involvement. Methods and results: Of 65 NA-ATLL patients (pts), 20 (30.77%) had CNS involvement by ATLL meeting above mentioned criteria. The median age of all pts in our dataset was 59 years. Pts were divided into non- CNS involved NA-ATLL (non-CNS NA-ATLL) and CNS involved NA-ATLL (CNS NA-ATLL) groups. Parameters to predict CNS involvement were outlined as leukocytosis (>11000 per microliter [μL]), elevated acute lymphocytic count (>4000/ μL), elevated lactate dehydrogenase (LDH) (>190 units/liter [u/l]), generalized lymphadenopathy (LAD) defined as involvement of 2 or more non-contiguous nodal sites, elevated corrected serum calcium levels (>10.5 mg/deciliter), bone marrow (bm) involvement and serosal involvement defined as pleural or peritoneal involvement. These variables were chosen given our prior work identifying them as critical to predict OS in our general NA-ATLL population. We then performed the Fisher test of proportions to determine if the variables above mentioned were different between the CNS NA-ATLL and the non-CNS NA-ATLL. We did not find significant associations when analyzing gender (p=0.0535), leukocytosis (p= 0.4001), lymphocytosis (p =0.57), hypercalcemia (p= 0.7661), elevated LDH (p= 0.4898), generalized LAD (p=0.271), serosal involvement (p= 0.05088) or bone marrow involvement (p=1). We only found a strong association when examining ATLL subtypes, being the acute/lymphomatous variant strongly associated with CNS involvement (p=2.226e10 -5). To identify variables that can have an impact in OS in CNS NA-ATLL vs non-CNS NA-ATLL we calculated Kaplan Meier survival curves. We did not find any difference based on age (p=0.23), gender (p=0.95), leukocytosis (p= 0.074), lymphocytosis (p =0.21), hypercalcemia (p= 0.094), elevated LDH (p= 0.37), generalized LAD (p=0.28), and serosal involvement (p= 0.1) in the overall survival. The only significant association we found was bone marrow involvement in predicting poor OS in CNS NA-ATLL group (p= 0.038). Next, we determined IPI scores (age>60, ECOG performance status>2, Ann Arbor stage III/IV, serum LDH score >190 u/L and more than 1 extra-nodal site) in our CNS NA ATLL and non-CNS NA ATLL cohorts. We sought to determine if: 1) this prognostication tool is predictive in NA-ATLL and 2) if these variables can be used to identify CNS involvement in our cohort. CNS pts with a higher IPI score (>3) showed tendency towards a lower survival rate (p=0.089) than non-CNS pts (p=0.3). IPI score of 3 or more was not predictive of CNS involvement in our sample (p=1). Conclusions: NA-ATLL is a rare and protean disease with poor prognosis and CNS involvement is prevalent. With the variables used we did not find clear predictors of CNS associated disease other than patients presented with the lymphomatous and acute subtypes. We also observed than bone marrow involvement portends a dismal prognosis for individuals with CNS involvement. Future studies with a larger cohort could provider further insight on discovering predictors for CNS involvement in NA ATLL. Figure 1 Figure 1. Disclosures Shah: Celgene/BMS: Research Funding; Janssen: Research Funding. Gritsman: iOnctura: Research Funding. Shastri: GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy; Onclive: Honoraria. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company. Janakiram: Amgen: Honoraria.

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Efficacy of a Brief, Cyclophosphamide-Intensive Regimen for Older Patients with Newly Diagnosed Burkitt's or Atypical Burkitt's Lymphoma/Leukemia.

Blood ◽

10.1182/blood.v114.22.2685.2685 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2685-2685

Author(s):

Yvette L. Kasamon ◽

Robert A. Brodsky ◽

Michael J. Borowitz ◽

Pamela A. Crilley ◽

Richard F. Ambinder ◽

...

Keyword(s):

Overall Survival ◽

Median Time ◽

Older Patients ◽

Research Funding ◽

Tumor Lysis Syndrome ◽

B Cell Lymphoma ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma ◽

High Dose ◽

Newly Diagnosed

Abstract Abstract 2685 Poster Board II-661 Background: Although standard therapies cure most adolescents and young adults with Burkitt's lymphoma/leukemia (BL), older patients (pts) have an inferior prognosis with an estimated 1-year survival of 50%. The inferior outcome is attributable to both insufficient efficacy and excess toxicity. Cyclophosphamide (Cy) has long been recognized to be arguably the most active agent in BL. Prior work at our institution showed that high-dose Cy, equivalent to transplantation doses, could be given without stem cell rescue with minimal toxicity even in older pts. Patients and Methods: A phase II trial for pts age ≥ 30, based on intensive Cy and incorporating rituximab but no anthracycline, was developed with a primary endpoint of 1-year overall survival. Entry requirements included newly diagnosed BL or atypical BL; any performance status (PS); HIV negative; and no significant cardiac dysfunction. Renal failure, even if necessitating dialysis, was permitted if it was acute. Treatment consisted of 3 cycles, with successive cycles beginning on day 15 or when ANC was ≥ 500/μL. Cycles 1 and 2 consisted of Cy 1500 mg/m2 IV day 1; vincristine 1.4 mg/m2 (2 mg cap) day 1; prednisone 100 mg days 1-5; rituximab 375 mg/m2 IV days 1 and 8; methotrexate 3 g/m2 IV day 8 with leucovorin rescue; cytarabine 100 mg intrathecally days 1, 4, and 11; and filgrastim. Cycle 3 consisted of rituximab 375 mg/m2 IV day 1; high-dose Cy (50 mg/kg IV days 2, 3, 4, and 5) with uroprotection; filgrastim; and rituximab 375 mg/m2 IV weekly for 4 weeks once ANC was ≥ 1000/μL. Eligibility for cycle 3 included ECOG PS < 4; no disease progression or uncontrolled meningeal disease; not on dialysis; and transaminases ' 5X upper limit of normal. Results: A prespecified interim analysis of the first 12 of a planned 20 evaluable pts is presented. Diagnosis was BL in 8 and atypical BL/unclassifiable high-grade lymphoma with features intermediate between BL and diffuse large B-cell lymphoma in 4. Median age was 56 (range 34 – 75), 8/12 (67%) had Ann Arbor stage III/IV disease, and all were high-risk by Magrath's criteria. PS ranged from 0 to 4. Two pts received hemodialysis on presentation. For all pts, actuarial event-free survival and overall survival (Figure) are 66% and 75%, respectively, at both 1 year and 2 years after treatment initiation. Three pts died during cycle 1: tumor lysis syndrome on day 1, neutropenic sepsis on day 8, multiorgan failure on day 46 after respiratory arrest on day 20. All of the other 9 pts completed protocol therapy: 8 (89%) achieved anatomic CR/CRu as well as a complete metabolic response by PET, and are event-free at a median of 29 months (range < 1 – 44 months) after therapy completion. The remaining pt had residual marrow disease followed by progression and is in remission 1 year after myeloablative allogeneic BMT. Adverse events in these 9 pts included 7 neutropenic fevers; 1 non-neutropenic bacteremia; and 1 self-limited episode of pericarditis with rapid atrial fibrillation. Grade 3 peripheral neuropathy was limited to 2 pts. The planned dose intensity was achievable: median time to cycle 2 was 15 days (14 – 21), and median time from start of cycle 1 to start of cycle 3 was 31 days (28 – 35). Median time to neutrophil recovery after the last dose of Cy was 16 days (10 – 21); median time to platelets ≥ 20,000/μL, without transfusion in the preceding week, was 22 days (0 – 30). Early stopping criteria for response or all-cause mortality have not been met. Conclusion: A very short regimen based on intensive Cy without anthracycline produces a high rate of durable CR's in older, poorer-risk pts with BL or atypical BL. Disclosures: Kasamon: Genentech: Research Funding. Swinnen:Genentech: Consultancy, Research Funding; Enzon: Consultancy; Abbot: Consultancy, Research Funding.

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How Many Life Years Have Been Saved In The United States From Using Rituximab Plus Chemotherapy Compared To Chemotherapy Alone From 1998-2013

Blood ◽

10.1182/blood.v122.21.2937.2937 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2937-2937

Author(s):

Mark Danese ◽

Michelle Gleeson ◽

Marc Halperin ◽

Sandra Skettino ◽

Carolina Reyes

Keyword(s):

United States ◽

Research Funding ◽

B Cell Lymphoma ◽

The United States ◽

Incidence Rates ◽

Lymphocytic Leukemia ◽

Age Group ◽

First Line ◽

Medicare Data ◽

Life Years

Abstract Introduction Rituximab was approved in December 1997 and has since become the standard of care in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). Clinical trials have shown statistically significant improvements in progression-free and overall survival. The objective of this study was to estimate the real-world effectiveness of first-line rituximab plus chemotherapy (R+Chemo) relative to chemotherapy alone (Chemo Alone) in the United States (US) from 1998 to 2013. Methods For each cancer, we constructed a population effectiveness model from 1998-2013 comprised of 3 modules: epidemiology, utilization and survival. The epidemiology module included age group, gender, and year-specific incidence rates for each cancer from the Surveillance, Epidemiology, and End Results (SEER) program from 2000-2010. Published SEER-based join-point estimates were used to extrapolate to other years. Census population data using the same age group, gender, and year strata were combined with incidence rates to project total diagnosed patient counts. The utilization module was based on SEER-Medicare linked data from 1999-2009. Drug utilization (defined as first infusion within 180 days of diagnosis for each cancer) for R+Chemo and for Chemo Alone was estimated as a proportion of all diagnosed patients, and stratified by age group, gender, and calendar year of diagnosis in the SEER-Medicare data. Utilization proportions were then multiplied by the diagnosed population counts to estimate treated patient counts for each cancer, by age group, gender, and calendar year. The survival module was calculated using SEER-Medicare data, starting from 30-days after first infusion, with follow up through 12/31/2010. For each cancer, flexible parametric (Royston-Parmar) survival models were applied to estimate restricted (10-year) mean survival times for each person, adjusted for individual patient covariates. These estimates were averaged across patients within strata defined by age group, gender and treatment. Life years lived were estimated for patients receiving R+Chemo, first by using mean survival for treatment with R+Chemo, and then by using mean survival estimates for Chemo Alone. The incremental life years saved were calculated as the difference between the projected survival from using R+Chemo and from using Chemo Alone. These differences were summed over age group, gender, and calendar year for each cancer. Monte Carlo sampling was used to estimate the 95% uncertainty intervals (UI). Results Across all three cancers, there were 289,793 cumulative life years saved (95% UI, 248,300-330,618; see Figure) from 1998 to 2013. For DLBCL, an estimated 177,952 patients were treated with R+Chemo. In these patients, an estimated 199,323 (95% UI 169,534-231,214) additional life years were lived compared to what might have occurred if Chemo Alone had been used instead. For FL, an estimated 84,303 patients were treated with R+Chemo, and an additional 80,338 (95% UI 53,876-106,709) life years were lived compared to Chemo Alone. For CLL, an estimated 14,398 patients were treated with R+Chemo, and an additional 10,132 (95% UI 4,469-15,998) life years were lived compared to Chemo Alone. Conclusions For DLBCL, FL and CLL patients treated with first-line therapy within 180 days of diagnosis in the US, approximately 290,000 cumulative life years were saved by adding rituximab to chemotherapy between 1998 and 2013. Next generation therapies may be able to extend these survival gains for patients with CLL, FL and DLBCL. Disclosures: Danese: Amgen: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding. Gleeson:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Halperin:Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Skettino:Genentech: Employment, stock Other. Reyes:Genentech, inc: Employment, Equity Ownership.

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ΝFΚΒΙΕ Deletions: A Novel Marker of Clinical Aggressiveness in Primary Mediastinal B-Cell Lymphoma

Blood ◽

10.1182/blood.v128.22.609.609 ◽

2016 ◽

Vol 128 (22) ◽

pp. 609-609

Author(s):

Daniel Noerenberg* ◽

Larry Mansouri* ◽

Emma Young ◽

Frick Mareike ◽

Maysaa Abdulla ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

High Frequency ◽

Research Funding ◽

Cell Lymphoma ◽

Gene Mutations ◽

B Cell Lymphoma ◽

Mutation Status ◽

Lymphoid Malignancies ◽

Ann Arbor

Abstract Deregulated NF-κB signaling is a hallmark of most, if not all, lymphoid malignancies, and recurrent gene mutations in both the canonical and non-canonical NF-κB pathway are known to lead to NF-κB activation. However, the full compendium of NF-κB gene mutations in lymphoid malignancies remains to be elucidated. Recently, we reported a 4-bp truncating mutation in the NFKBIE gene, which encodes IκBε, a negative regulator of NF-κB, in patients with chronic lymphocytic leukemia (CLL). The NFKBIE deletion was enriched in clinically aggressive CLL patients (7-8%) and associated with a worse clinical outcome. At the functional level, NFKBIE-deleted CLL showed reduced IκBε levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65, compared to wildtype patients. Preliminary data has indicated an increased frequency of NFKBIE aberrations in other lymphoid malignancies as well. To explore this further, we screened for NFKBIE deletions in a large cohort of patients diagnosed with a range of different lymphoid neoplasms. Overall, NFKBIE deletions were identified in 76 of 1414 patients (5.4%). While NFKBIE deletions were relatively infrequent in patients diagnosed with follicular lymphoma (3/225, 1.3%), splenic marginal zone lymphoma (3/175, 1.7%), and T-cell acute lymphoblastic leukemia (1/94, 1.1%), moderate frequencies were observed among diffuse large B-cell lymphoma (18/521, 3.5%), mantle cell lymphoma (8/189, 4.2%), and primary CNS lymphoma (1/34, 2.9%) patients. In contrast, a remarkably high frequency of NFKBIE deletions (41/176 cases, 23%) was observed among primary mediastinal B-cell lymphoma (PMBL) patients. Noteworthy, the prevalence of NFKBIE-deleted PMBL cases was similar in the different contributing centers. All PMBL patients in the present series received a CHOP based treatment regime; in ~75% of cases rituximab was added and ~25% were treated with dose intensified schemes. For the latter, the vast majority of patients received CHOEP, while individual cases were treated with MegaCHOEP, DA-EPOCH or ACVBP. Regarding clinicobiological associations, there were no significant differences between NFKBIE-deleted and wildtype PMBL patients with respect to age, sex, Ann Arbor stage, IPI risk-groups, extranodal or bone marrow involvement, bulky disease, and LDH elevation. However, NFKBIE-deleted patients were more likely to be refractory to primary chemotherapy (31% vs. 3%, P=.001) and had a shorter overall survival compared to wildtype patients (5-year overall survival: 63% vs 84%, P=.013). In multivariate analysis (including age, gender, Ann Arbor stage, IPI, and NFKBIE mutation status), NFKBIE mutation status (95% CI: 1.23-10.61; HR: 3.61; P=0.020) remained an independent factor for poor prognosis. In summary, we document NFKBIE deletions as a common genetic event across B-cell malignancies, albeit at varying frequencies. The high frequency of NFKBIE deletions in PMBL alludes to the critical role of this aberration in the pathophysiology of the disease. NFKBIE deletions were associated witha worse clinical outcome, hence potentially representing a novel poor-prognostic marker in PMBL. *Contributed equally as first authors. **Contributed equally as senior authors. Disclosures Stamatopoulos: Gilead: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria, Other: Travel expenses; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Other: Travel expenses, Research Funding.

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Insurance Status Impacts Survival in Burkitt Lymphoma

Blood ◽

10.1182/blood.v130.suppl_1.916.916 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 916-916

Author(s):

Jordan S. Goldstein ◽

Jeffrey M. Switchenko ◽

Madhusmita Behera ◽

Christopher Flowers ◽

Jean L. Koff

Keyword(s):

United States ◽

Research Funding ◽

Private Insurance ◽

The United States ◽

Insurance Status ◽

Proportional Hazard ◽

Comorbidity Score ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Models ◽

Insured Patients

Abstract Introduction: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma with an estimated 1480 new cases diagnosed in the United States in 2016. BL is simultaneously one of the most aggressive lymphomas, with a tumor volume doubling time of just 24 hours, and one of the most curable, with several clinical trials showing 3-year survival rates over 80%. However, recent studies have identified a significant discrepancy between clinical trial and "real-world" survival, implying access to care may play an important role in BL outcomes. A patient's insurance status represents a major factor in the utilization of cancer therapies and outcomes in the United States. Underinsured patients are more likely to be diagnosed at an advanced stage, receive substandard therapy, and have worse outcomes. We examined the effect of insurance status on survival in adults with BL and compared the impact of insurance status on BL outcomes to that seen in plasmablastic lymphoma (PBL), an aggressive lymphoma that has poor outcomes regardless of treatment. Methods: We used data from the National Cancer Database (NCDB), a nationwide, hospital-based cancer registry jointly sponsored by the American Cancer Society and American College of Surgeons that contains 34 million historical records and captures 75% of newly diagnosed cancer cases in the United States. Commission on Cancer (CoC)-accredited facilities report patients' vital status and date of death to the NCDB annually. We included patients > 18 years old diagnosed 2004-2014 with BL or PBL as the primary tumor who received all or part of initial course of treatment at the reporting facility. Patients missing information on insurance status or survival were excluded, as were those who had non-Medicare/Medicaid government insurance (VA, Indian Health Services). Chi-square tests were used to compare sociodemographic and clinical characteristics by insurance status. All analyses were performed for both BL and PBL and stratified on age 65, due to changes in eligibility for Medicare at that age. Kaplan-Meier survival curves were stratified by insurance status, and log-rank tests were performed. Univariate Cox proportional hazard models were generated to describe the unadjusted associations for the covariables, and multivariable Cox proportional hazard models were generated to estimate the hazard ratio (HR) associated with insurance status when adjusted for prognostic factors. Results: We identified 7,073 BL patients and 475 PBL patients in the NCDB who met inclusion criteria. Of the 5235 BL patients < 65 years, 65.0% had private insurance, 17.2% had Medicaid, 7.6% had Medicare, and 10.2% had no insurance. Of the 1838 BL patients ≥ 65 years, 12.9% had private insurance, 1.5% had Medicaid, 85% had Medicare, and 0.65% had no insurance. Uninsured and Medicaid-insured patients were more likely to be Hispanic or black, have lower socioeconomic status (SES), have B symptoms, be HIV-positive, and have a Charlson-Deyo comorbidity score ≥ 2 when compared with privately insured patients. Medicare patients were more likely to be female, have ≥1 comorbidity, and not receive chemotherapy treatment when compared to privately insured patients. BL patients without private insurance had significantly worse overall survival compared to those with private insurance, regardless of age group (adjusted HR age <65: uninsured 1.41 [95% confidence interval 1.2,1.7], Medicaid 1.17 [1,1.4], Medicare 1.5 [1.2,1.8]; adjusted HR age ≥ 65: uninsured 6 [2.1,17.3], Medicare 1.33 [1,1.8]; see Figure). Conversely, Cox regression models demonstrated that PBL patients without private insurance experienced no significant differences in overall survival in either age group. For BL patients age <65, low SES, presence of B symptoms, advanced stage, HIV-positive status, comorbidity score ≥ 2, and lack of treatment were significant, independent predictors of worse outcomes and contributed to the disparities in survival by insurance status. For BL age > 65, B symptoms, comorbidity score ≥ 2, and lack of treatment were significant, independent predictors of worse outcomes. Conclusion: We identified insurance status as an important predictor of clinical outcomes for BL. Our findings suggest that expanding access to care may improve survival disparities in BL, for which curative therapy exists, but not PBL, where more effective therapies are needed to improve outcomes. Disclosures Flowers: Celgene: Consultancy, Research Funding; Bayer: Consultancy; V Foundation: Research Funding; Research to Practice: Research Funding; Infinity: Research Funding; Acerta: Research Funding; National Institutes Of Health: Research Funding; Clinical Care Options: Research Funding; Educational Concepts: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; OptumRx: Consultancy; Spectrum: Consultancy; Genentech/Roche: Consultancy, Research Funding; National Cancer Institute: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Onyx: Research Funding; Burroughs Welcome Fund: Research Funding; TG Therapeutics: Research Funding; Prime Oncology: Research Funding; Millennium/Takeda: Research Funding; Janssen Pharmaceutical: Research Funding; Seattle Genetics: Consultancy; Gilead: Consultancy.

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The Neutrophil-to-Lymphocyte Ratio Is Prognostic in Patients with Diffuse Large B-Cell Lymphoma: A Study from the Latin American Group of Lymphomas (GELL)

Blood ◽

10.1182/blood-2018-99-113246 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2987-2987

Author(s):

Brady E. Beltrán ◽

Victoria Otero ◽

Marialejandra Torres Viera ◽

Camila Peña ◽

Myriam Lucía Rodriguez ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

B Cell ◽

Latin American ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Entire Group ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Introduction: Diffuse large B-Cell Lymphoma (DLBCL) is the most frequent subtype of lymphoma in the world. The IPI score is a powerful risk-stratification tool in patients with DLBCL. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with DLBCL in Asia, Europe and USA. The GELL is a recently formed group for the study of lymphomas in Latin America composed by large institutions from eleven countries. The aim of this study was to evaluate whether the NLR is a prognostic factor in Latin American patients with DLBCL. Methods: We included patients with a pathological diagnosis of DLBCL who were diagnosed and treated at our institution between 2012-2013. IRB approval was obtained prior to research, and pathological samples were reviewed by hematopathologists at each of the participating institutions to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the absolute lymphocyte count and dichotomized in NLR≥4 and NLR<4. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for overall survival (OS). Results: A total of 329 patients with a diagnosis of DLBCL were included in this analysis. The median age at diagnosis was 64 years (range 18-83 years) with a slight female predominance (54%). Clinically, 59% of patients were 60 or older, 34% had ECOG >1, 29% had elevated LDH, and 70% had extranodal disease; 49% had early stage and 51% had stage III and IV. The IPI score was low risk in 36%, low-intermediate in 25%, high intermediate in 22% and high risk in 17%. 41% of patients had NLR ≥4. 89% of patients received standard R-CHOP, 2% received R-miniCHOP and 9% received other regimens. The overall response rate as 83%; 69% had complete response and 14% had partial response. The median follow-up for the entire group was 5 years (95% CI 4.9-5.4 years). The 5-year overall survival (OS) rate for the entire group was 65%. The 5-year OS rates for patients with NLR ≥4 and <4 were 59% and 71%, respectively (p=0.008). Patients with low, low-intermediate, high-intermediate and high IPI scores had 5-year OS rates of 80%, 65%, 56% and 45%, respectively (p<0.001). In the multivariate analysis, advanced stage (HR 3.1, 95% CI 1.9-5.0; p<0.001), LDH level (HR 2.2, 95% CI 1.2-4.2; p=0.016) and NLR ≥4 (HR 1.7, 95% CI 1.1-2.6; p=0.03) were statistically independent factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for IPI score (HR 1.7, 95% CI 1.1-2.6; p=0.01). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS, independent of the IPI score, in previously untreated Latin American patients with DLBCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with DLBCL. Figure. Figure. Disclosures Chiattone: Janssen: Honoraria, Research Funding. Castillo:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Genentech: Consultancy.

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Extended Use of Rituximab in Older Adults with Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v124.21.1279.1279 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1279-1279

Author(s):

Matthew J. Matasar ◽

Coral L. Atoria ◽

Elena B. Elkin ◽

Chadi Nabhan

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Rural Areas ◽

Research Funding ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

The United States ◽

Non Hodgkin Lymphoma ◽

To Receive

Abstract Background: The introduction of rituximab has improved outcomes in B-cell non-Hodgkin lymphoma (BCL) across all histologies. Extended use of rituximab, or maintenance rituximab, improves progression-free survival in follicular lymphoma (FL) patients who achieve a response to induction rituximab with or without chemotherapy, but there is no evidence of an overall survival benefit. There is currently little evidence to support extended use of rituximab in other histologic subgroups, and older patients in particular may be at risk of adverse events. Our objective was to characterize patterns and predictors of extended rituximab therapy in a population-based cohort of older BCL patients in the United States. Methods: In the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset,we identified patients 66 years and older diagnosed with BCL in 2000-2010. Histology was classified as diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), FL, mantle cell lymphoma (MCL), other indolent BCL, and BCL not otherwise specified (NOS). We identified Medicare claims for rituximab starting at any point following diagnosis. Extended rituximab therapy was defined as a duration of greater than 7 months with no gap in rituximab claims greater than 6 months. Demographic and clinical characteristics associated with extended rituximab were evaluated in multivariable logistic regression. Results: There were 24,232 BCL patients who received rituximab during the study period. The cohort was predominantly white (91%), half were men, 15% had a Charlson comorbidity score ≥2, and 12% were 85 years or older. DLBCL was the most common histology (44%), followed by FL (21%), other indolent BCL (17%), BCL-NOS (13%), MCL (6%), and BL (1%). Overall, most patients (85%) received rituximab for ≤7 months, but duration varied by histology (Table 1). More than a quarter of FL patients had extended therapy, including 7% who had rituximab for more than 24 months. Among patients with other histologies, receipt of extended therapy varied from 20% (other indolent BCL) to 8% (BL). Compared with FL patients and controlling for demographic and disease characteristics, patients with other histologies were less likely to receive extended rituximab therapy (p<0.0001). Adjusted odds ratios were 0.91 (95% CI 0.78-1.05) for MCL, 0.83 (0.75-0.91) for other indolent BCL, 0.67 (0.60-0.75) for BCL-NOS, 0.32 (0.29-0.36) for DLBCL, and 0.28 (0.15-0.53) for BL. However, 75% of patients who had extended rituximab, and 63% of those who had rituximab >24 months, were of non-FL histology. Controlling for histology and other characteristics, extended rituximab therapy was more likely among women (adjusted OR 1.09, 95% CI 1.01-1.18), and less likely among unmarried patients (0.92, 0.85-0.99) and those in rural areas (0.84, 0.75-0.94). There was significant regional variation (p<0.0001), with patients in the West (adjusted OR 0.86, 95% CI 0.79-0.95), and Midwest (0.75, 0.66-0.86) less likely to receive extended rituximab than those in the Northeast. There was no significant relationship between extended therapy and age, race, or comorbidity. Conclusions: While FL patients were more likely than others to receive extended rituximab, the majority of patients receiving extended rituximab had other diagnoses across the entire spectrum of B-cell lymphoma, for which extended rituximab is neither indicated nor supported by guidelines or prospective data. After controlling for histology, several demographic characteristics significantly influenced the duration of therapy. Extended use of rituximab – particularly in patients for whom it is not clearly indicated – may have important implications for clinical outcomes, toxicity, and costs. Table 1 Duration of rituximab use across B-cell lymphoma histologic subgroups Histology Duration of Rituximab N ≤7 mos >7-24 mos >24 mos DLBCL 10,567 91% 7% 2% FL 5,001 76% 17% 7% BL 127 92% 6% 2% MCL 1,339 79% 16% 5% Other indolent 4,095 80% 15% 5% BCL NOS 3,103 83% 13% 4% Total 24,232 80% 15% 5% Disclosures Matasar: Merck: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Honoraria; Spectrum: Honoraria. Nabhan:Celgene: Honoraria, Research Funding.

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Short Time between Progression after Immunochemotherapy and Initiation of Salvage Therapy (PTI) Is Associated with Inferior Long-Term Outcomes in Patients with Relapsed/Refractory DLBCL

Blood ◽

10.1182/blood-2018-99-114331 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4204-4204 ◽

Cited By ~ 1

Author(s):

Matthew J. Maurer ◽

Umar Farooq ◽

Madison M Wahlen ◽

Thomas M. Habermann ◽

Gita Thanarajasingam ◽

...

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Selection Bias ◽

Salvage Therapy ◽

Research Funding ◽

B Cell Lymphoma ◽

Salvage Chemotherapy ◽

Aggressive Disease ◽

Treatment Interval ◽

Biopsy Confirmation

Abstract Background An association has been identified between the diagnosis-to-treatment interval (DTI) and prognostic clinical factors and outcomes in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Maurer et al, JCO 2018). This association can result in inadvertent selection bias in clinical trials to exclude patients with aggressive disease due to the inability to delay treatment long enough to fulfill enrollment criteria, compromising the validity of clinical trial study results to the general population. A similar concern exists in the relapsed/refractory (r/r) DLBCL setting regarding patient selection bias against patients with aggressive disease requiring immediate treatment following relapse or progression. Here we examine the time from progression after immunochemotherapy (IC) to the initiation of first salvage chemotherapy and its association with outcome. Patients and Methods: Newly diagnosed patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER), now a subcohort of the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study, and followed for progression/relapse, retreatment, and death. This analysis includes patients with their first r/r DLBCL following frontline IC who initiated aggressive salvage chemotherapy as identified and included in a previous publication (Farooq et al, BJH 2017). The progression-to-treatment interval (PTI) was defined as the time in days from date of progression from IC to initiation of salvage therapy. The date of progression was defined as either a) the date biopsy was obtained for patients who had a biopsy to confirm progressive disease or b) the date of the scan or clinical examination indicating progression in patients who did not have a biopsy performed. Event-free survival (EFS) was defined as time from initiation of first salvage therapy to progression or relapse, initiation of new anti-lymphoma therapy, or death due to any cause; overall survival (OS) was defined as time from initiation of salvage therapy until death due to any cause. Results: 162 patients with r/r DLBCL enrolled in the MER from 2002-2012 who initiated aggressive salvage chemotherapy with intent to transplant and had confirmed dates for both progression after IC and start of salvage therapy were evaluated. Median age at first progression for these patients was 64 years (range 36-76) and 104 (64%) were male. Median time from diagnosis to first progression on IC was 6.7 months (IQR: 4.6-12.7). Initial salvage therapy was R-ICE (80%), R-DHAP (8%), rituximab, oxaliplatin, cytosine arabinoside, and dexamethasone (ROAD) (6%), and other (7%). At a median follow-up of 49 months from initiation of salvage therapy (IQR: 33-74), 116 patients had died (72%). Median PTI was 6 days (IQR: 2-13). 110 patients (68%) had biopsy confirmation of disease prior to initiating salvage therapy; median PTI was 2 days (IQR: 1-7) for patients who had biopsy confirmation vs. 7 days (IQR: 3-16) in patients without biopsy confirmation, Wilcoxon p=<0.0001. There was no difference in OS from initial salvage therapy between patients who did not have biopsy confirmation (HR=1.09, 95% CI: 0.74-1.60, p=0.68) compared to patients with biopsy confirmation. Patients with short PTI (0-6 days) had significantly worse overall survival from initiation of salvage therapy (median OS = 7.6 months, HR=2.10 (95% CI: 1.43-3.08) compared to patients who initiated therapy 7 or more days from progression (median OS = 29.7 months), logrank p<0.0001. This association remained consistent (HR=2.20, 95% CI: 1.48-3.26, p<0.0001) after adjusting for age and biopsy confirmation of progression. Short PTI was also associated with inferior response rate to initial salvage therapy (51% vs. 65%, p=0.058), lower rate of proceeding to transplant after initial salvage therapy (33% vs. 55%, p=0.0063), lower rate of being event-free 24 months from initial salvage therapy (16% vs 33%, p=0.011) and lower rate of ever proceeding to transplant (44% vs. 59%, p=0.057). Conclusions: A short progression-to-treatment interval is strongly associated with inability to proceed to transplant and inferior overall survival in r/r DLBCL. These results have implications for the design and interpretation of clinical trials in the relapsed/refractory setting. Figure. Figure. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Ansell:Trillium: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Pfizer: Research Funding; Celldex: Research Funding; Takeda: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Nanostring: Research Funding; Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board.

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Clinical Features and Outcomes of Isolated Myeloid Sarcoma in the United States: Analysis Using a National Dataset

Blood ◽

10.1182/blood.v128.22.1618.1618 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1618-1618

Author(s):

Gaurav Goyal ◽

Adam C Bartley ◽

Aref Al-Kali ◽

William J Hogan ◽

Mark Litzow ◽

...

Keyword(s):

United States ◽

Overall Survival ◽

Research Funding ◽

Median Overall Survival ◽

Case Series ◽

The United States ◽

Myeloid Sarcoma ◽

Anatomical Distribution ◽

Mediastinal Disease ◽

Significant Difference

Abstract Introduction Isolated myeloid sarcoma is a rare form (<1%) of acute myeloid leukemia presenting as extramedullary tumor. Contemporary clinical data are mostly limited to institutional case series. Using the National Cancer Database, the largest public cancer registry covering >70% of all newly diagnosed cancers in the United States, we determined the patterns of anatomical presentation and clinical outcome of myeloid sarcoma. Methods We identified patients with a histologically confirmed diagnosis of isolated myeloid sarcoma from 2004-2013 using International Classification of Diseases for Oncology version 3 (ICD-O-3) code: 9930. To allow at least 1 year of follow-up, only patients diagnosed from 2004-2012 were included in the survival analysis using Kaplan-Meier estimates. Results A total of 746 patients were included in the study. The median age of patients was 59 years (range, 41 to 73) and 56% were males. The anatomical distribution and median overall survival of patients are depicted in the Table. The top 3 most common sites of presentation were connective/soft tissues (31.3%), skin/breast (12.3%), and digestive system (10.3%). Compared to other races, Blacks were more likely to have presentation in bones/joints (11.8% vs 6.3% in others), lymph nodes/spleen (22.1% vs. 9%), and less likely in skin/breast (4.4% vs. 13.8%). Asians were more likely to present with cardiopulmonary/mediastinal disease as compared to other races (13.6% vs. 4.2%). According to outcomes, we can categorize the patients into 3 groups: good (median overall survival >30 months: reproductive and digestive systems), intermediate (median overall survival 15-30 months: head/neck and kidney/bladder/retroperitoneum/adrenal), and poor (median overall survival <15 months: nervous system, connective/soft tissue, and bones/joints). There was no significant difference in overall survival between males and females (P =0.06). Among the races, Blacks had the worst overall survival (P =0.02; Figure). Conclusions This is the largest registry-based study on isolated myeloid sarcoma in the United States. Isolated myeloid sarcoma has a diverse anatomic clinical presentation and the overall survival varied significantly according to sites of presentation and racial subgroups. The results of our study may aid the prognostication of patients for treatment decision making and in the understanding of the biological differences by anatomic sites of presentation. Table Anatomical distribution and median overall survival of isolated myeloid sarcoma Table. Anatomical distribution and median overall survival of isolated myeloid sarcoma Figure Overall survival by sex and race in isolated myeloid sarcoma Figure. Overall survival by sex and race in isolated myeloid sarcoma Disclosures Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

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