Exploring Disease Biology in Hispanic Versus Non-Hispanic Patients with Diffuse Large B-Cell Lymphoma (DLBCL) to Explain Survival Disparities

Abstract Background: DLBCL is the most common adult NHL and despite significant advancements, outcomes in ethnic minorities remain suboptimal. Factors responsible for these disparities in ethnic minorities, especially variability in clinical and pathological features with evaluation of patient-level data have not been studied. Methods: A multi-institutional database of DLBCL patients seen at Mayo Clinic in Florida, University of Miami and University of Southern California between 1996-2016 was developed. Patient demographics, clinical disease characteristics and details of DLBCL immunophenotype [CD10, MUM1, BCL6 (Han's classification), Ki 67, MYC, BCL2) were reviewed. Comparisons between Hispanic and Non-Hispanic patients were made by Chi-square, Fischer's exact and Signed rank tests, where applicable. Patients with missing data on a certain feature were not included in the statistical analysis of that specific characteristic. Results: A total of 966 DLBCL patients with 69 Hispanics and 752 non-Hispanics were identified. These included 52% males (N=36) and 48% females (N=33) in Hispanics versus 58% males (N=436) and 42% females (N=316) in Non-Hispanics (p=0.35). Median age at diagnosis was significantly lower at 61 years (range 27-89) in Hispanics versus 66 in non-Hispanics (p=0.014). Extranodal disease was seen significantly more commonly in Hispanics (74%) than in non-Hispanics (60%) (p=0.037). There was no significant difference in disease stage at presentation between the two cohorts (p=0.189) although the proportion of patients with stage III and IV disease was higher among Hispanics (80.4%) as compared to non-Hispanics (68.5%). Similarly there was no significant difference in presence of primary CNS DLBCL at diagnosis between the two groups (p=0.74). GCB phenotype per the Hans' classification was seen in 59% (N=29) in both, Hispanics and Non-Hispanics (N=241) (p=0.99). Similarly, the median ki67 index of 80% was seen in both cohorts (p=0.48). MYC was positive in 59% in Hispanics versus only 37.5% in non-Hispanics (p=0.024). BCL2 expression by itself and also combined BCL2 and MYC double expression were not significantly different between the two groups (p=0.58 and p=0.11, respectively). Median overall survival (OS) was 22.5 months in Hispanics compared 54.9 months in Non-Hispanics (p<0.0001) (Figure 1). Conclusion: Survival outcome disparities in racial and ethnic minorities have been previously reported from population-based analyses. Lack of patient-level clinical data makes these analyses hypothesis generating, but not conclusive. We confirmed some prior findings including younger age at diagnosis for Hispanics with DLBCL. We also reported greater incidence of extranodal as well as stage III or IV disease at the time of presentation among Hispanics which may contribute to poor outcomes in this population. From DLBCL pathology standpoint, we found increased expression of MYC among Hispanics but no other significant immunohistochemical differences including double expression or non-GCB phenotype. The inferior OS despite uniform treatment practices at large Cancer Centers suggest multifactorial influences on patient outcomes which may at least in part include some of the differences we report here. Disclosures Ailawadhi: Pharmacyclics: Research Funding; Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy.

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Racial disparity in KRAS mutation frequency and outcomes in colorectal cancer (CRC): A U.S. population based study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.18 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 18-18

Author(s):

Jeffrey Bien ◽

Mayada Aljehani ◽

Jerry S.H. Lee ◽

Albert Y. Lin

Keyword(s):

Racial Disparity ◽

Kras Mutation ◽

Mutation Frequency ◽

Population Based ◽

Mutation Status ◽

Risk Increase ◽

Kras Status ◽

Significant Difference ◽

Hispanic Patients ◽

Race Ethnicity

18 Background: Racial disparity in CRC survival outcome is well documented. Although the reasons for disparity are unclear, a combination of differences in access to care, quality of care, differential treatment response, and underlying cancer biology are implicated. Further, recent studies have observed differences in KRAS mutation frequency between race/ethnic groups. KRAS mutation in metastatic CRC portends a worse response to EGFR-directed therapy, and predicts a poorer prognosis. In this study, we examined whether racial/ethnic differences in KRAS mutation frequency might impact CRC outcomes on a population-based level. Methods: We examined data from 202,237 CRC patients in the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The differences in tumor mutation status by stage and race/ethnicity were examined by χ2 testing. Cause-specific survival (CSS) and overall survival by mutation status were plotted by Kaplan-Meir curves. A multivariable Cox-proportional hazards model was used to construct hazard ratios and 95% confidence intervals (CI) using patient demographics, tumor characteristics, and KRAS mutation status. Results: Overall, about 9% of patients (n = 18,248) in the SEER registry had KRAS status available. In this cohort, tumors from Non-Hispanic Black (NHB) (48%) or Hispanic patients (44%) carried a greater KRAS mutation (mKRAS) rate when compared against Non-Hispanic White (NHW) (39%) or Asian or Pacific Islander (API) patients (37%) (p < 0.01). The assessment of the impact of mKRAS within each race/ethnic group, comparing patients with mKRAS versus wild-type KRAS (wKRAS) on CSS risk show a 7% risk increase for NHW, (HR = 1.07; 95%CI:1.02-1.12), a 15% risk increase for NHB, (HR = 1.15; 95%CI:1.04-1.26) and no significant increase among API, (HR = 1.02; 95%CI:0.92-1.4). Among patients with wKRAS, with NHW for reference, the risk of CSS is 11% higher among NHB (HR = 1.11; 95%CI:1.00-1.23), 14% higher for Hispanic, (HR = 1.14; 95%CI:1.02-1.26) and no significant difference observed among API, (HR = 1.03; 95%CI:0.91-1.16). Evaluation of the interaction between race/ethnicity and KRAS status on the CSS risk shows an increase of: 11% for mKRAS NHW, (HR = 1.11; 95%CI:1.00-1.23), 13% risk for NHB (HR = 1.13; 95%CI:1.01-1.25), 11% for Hispanic wKRAS, (HR = 1.11; 95%CI:1.04-1.18), 31% for Hispanic mKRAS (HR = 1.31; 95%CI:1.18-1.145), 16% for wKRAS API (HR = 1.16; 95%CI:1.03-1.29). In contrast, no significant difference in risk is seen for NHB nor API patients, HR = 1.02 (95%CI:0.90-1.14) and 1.04 (95%CI:0.91-1.20) respectively. Conclusions: mKRAS, compared to wKRAS, connotes worse CSS among NHW and NHB patients. Among wKRAS, NHB and Hispanic patients still experience higher mortality risk. This data suggests the negative prognosis heretofore associated with mKRAS may be linked to race/ethnicity and worthy of further study.

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Conditional Survival and Cure of Patients With Colon or Rectal Cancer: A Population-Based Study

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2020.7568 ◽

2020 ◽

Vol 18 (9) ◽

pp. 1230-1237 ◽

Cited By ~ 1

Author(s):

Seyed M. Qaderi ◽

Paul W. Dickman ◽

Johannes H.W. de Wilt ◽

Rob H.A. Verhoeven

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Population Based ◽

Stage I ◽

Stage Iii ◽

Disease Stage ◽

Conditional Survival ◽

Population Based Study ◽

Pathologic Stage ◽

Number Of Patients

Background: The increasing number of colorectal cancer (CRC) survivors need survival estimates that account for the time already survived. The aim of this population-based study was to determine conditional survival, cure proportions, and time-to-cure (TTC) of patients with colon or rectal cancer. Materials and Methods: All patients with pathologic stage I–III CRC treated with endoscopy or surgery, diagnosed and registered in the Netherlands Cancer Registry between 1995 and 2016, and aged 18 to 99 years were included. Conditional survival was calculated for those diagnosed before and after 2007. Cure proportions were calculated using flexible parametric models. Results: A total of 175,384 patients with pathologic stage I (25%), II (38%), or III disease (37%) were included. Conditional 5-year survival of patients with stage I, II, and III colon cancer having survived 5 years was 98%, 94%, and 92%, respectively. For patients with stage I–III rectal cancer, this was 96%, 89%, and 85%, respectively. Statistical cure in patients with colon cancer was reached directly after diagnosis (stage I) to 6 years (stage III) after diagnosis depending on age, sex, and disease stage. Patients with rectal cancer reached cure 0.5 years after diagnosis (stage I) to 9 years after diagnosis (stage III). In 1995, approximately 42% to 46% of patients with stage III colon or rectal cancer, respectively, were considered cured, whereas in 2016 this percentage increased to 73% to 78%, respectively. Conclusions: The number of patients with CRC reaching cure has increased substantially over the years. This study’s results provide valuable insights into trends of CRC patient survival and are important for patients, clinicians, and policymakers.

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Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in Uruguay: A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.53 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 53-53

Author(s):

Santiago Fontes ◽

Ana Marín-Jiménez ◽

Megan Berry ◽

Mauricio Cuello ◽

Juan Carlos Sánchez ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Practice ◽

Adjuvant Chemotherapy ◽

Clinical Practice Guidelines ◽

Practice Guidelines ◽

Population Based ◽

Stage Iii ◽

Disease Stage ◽

Curative Intent ◽

Factors Associated

53 Background: Despite surgery, the 5-year risk of systemic recurrence of colorectal cancer (CRC) in the absence of any further therapy is approximately 50 % for those with lymph node involvement and 20 ─ 30 % if the lymph nodes are negative. Adjuvant chemotherapy contributes to improved disease-free and overall survival for node-positive (stage III) or high-risk node negative (stage IIB) colon cancer. Similar benefits are observed for adjuvant chemoradiotherapy in rectal cancer. Previous research shows varied rates of adherence to published adjuvant chemotherapy Clinical Practice Guidelines (CPGs) for CRC, although population-based data is scarce. Purpose: The aim of this analysis was to assess adherence rates to adjuvant chemotherapy prescription within 16 weeks of surgery according to local and international CPGs for CRC patients treated with curative intent between 2008 and 2019 at the Uruguayan National Cancer Institute. Data regarding factors associated with chemotherapy receipt beyond 16 weeks from surgery and chemotherapy non receipt was also retrieved and analysed. Methods: We retrospectively reviewed medical and pathology reports of 833 patients diagnosed with CRC at our institution. Patients with stages IIB or III CRC who underwent curative-intent surgery were identified and included in the present analysis. A 16-week benchmark timeline for treatment initiation from date of surgery was considered. Fisher’s exact test was used to determine factors independently associated with receipt of chemotherapy and meeting the 16-week benchmark (p 0.05). Results: A total of 400 patients were identified of which 72% had peritoneal colorectal tumors and 28% had sub-peritoneal rectal tumors. Approximately 70% of the latter group received neoadjuvant chemo-radiotherapy. Considering the total cohort, 61% received adjuvant chemotherapy. Factors predicting chemotherapy receipt in the peritoneal colorectal group were age ≤ 70 and stage III disease. In the sub-peritoneal rectal group no significant effect was found. The 16-week benchmark was met in 72% (175) of those receiving chemotherapy and 70.6% (167) completed 6 months of systemic adjuvant treatment. A total of 156 patients (39%) did not receive adjuvant chemotherapy. The factors predicting chemotherapy non receipt were age > 70 and stage IIB in the peritoneal colorectal group. Conclusions: This analysis of adherence to CPGs identified several factors associated with chemotherapy non receipt and chemotherapy receipt outside of timeline benchmarks from date of curative-intent surgery in Montevideo, Uruguay. The two main factors significantly associated with chemotherapy non receipt were advanced age and lower disease stage. To our knowledge, our data is the first to elucidate these specific factors in the Uruguayan CRC patient population.

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Report of clinico-pathological features of breast cancer in HIV-infected and uninfected women in Botswana

Infectious Agents and Cancer ◽

10.1186/s13027-019-0245-6 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Rohini K. Bhatia ◽

Mohan Narasimhamurthy ◽

Yehoda M. Martei ◽

Pooja Prabhakar ◽

Jeré Hutson ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Stage Iii ◽

Disease Stage ◽

Breast Cancers ◽

Pathological Features ◽

Breast Cancer Patients ◽

Hiv Status ◽

Receptor Status ◽

Significant Difference

Abstract Background To characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status. Methods This was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records. Results A total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44–66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER−/PR−/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER−/PR−/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals. Conclusions Majority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.

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Superior Survival after Autologous vs. Allogeneic Hematopoietic Stem Cell Transplantation (HCT) for Diffuse Large B-Cell Lymphoma (DLBCL) Not Explained by Differences in Chemosensitivity.

Blood ◽

10.1182/blood.v108.11.3021.3021 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3021-3021

Author(s):

Brandon Hayes-Lattin ◽

Jeanette Carreras ◽

Mei-Jie Zhang ◽

Koen van Besien ◽

Julie M. Vose ◽

...

Keyword(s):

B Cell Lymphoma ◽

Older Age ◽

Disease Stage ◽

Hematopoietic Stem ◽

Post Transplant ◽

Significant Difference ◽

Risk Of Progression ◽

The Difference ◽

Induction Failure ◽

Autologous Hct

Abstract No randomized trials have compared autologous HCT (autoHCT) to allogeneic HCT (alloHCT) for DLBCL. We analyzed the outcomes of 916 patients (pts) (837 autoHCT and 79 alloHCT) ages 18–60yrs after a first autoHCT or HLA-identical sibling alloHCT for DLBCL between 1995 and 2003 reported to the CIBMTR. Pts receiving T-cell depleted allografts or reduced-intensity conditioning were excluded. There were significant baseline differences between the groups in disease stage, B symptoms, extranodal disease and marrow involvement. AlloHCT pts were significantly more likely to have >3 chemo regimens prior to HCT (53 vs 40%), and resistant induction failure or relapse (39 vs 16%). At 1yr, treatment-related mortality (TRM) was higher after alloHCT (41%, 95% CI, 30–52%) than after autoHCT (11%, 95% CI, 9–14%, p<0.001), but risks of relapse/progression were similar (30%, 95% CI, 21–41%) and (33%, 95% CI, 29–36%, p=0.69), respectively. Cumulative incidence of outcomes and univariate probabilities of progression free (PFS) and overall survival (OS) at 5 yrs are summarized in table 1. In multivariate analysis, allo and autoHCT had differential early and late effects on outcomes. In the first 12 mo after transplant, alloHCT was associated with higher TRM (RR 4.76, 95% CI, 3.14–7.22, p<0.001), treatment failure (RR 2.08, 95% CI, 1.56–2.77, p<0.001) and mortality (RR 2.78, 95% CI, 2.06–3.77, p<0.001) but similar risk of progression (RR 1.14, 95% CI, 0.75–1.74, p=0.54) compared to autoHCT. Among pts surviving 12 mo post-transplant, no significant difference was observed between autoHCT and alloHCT for TRM, progression, PFS, or OS. Covariates that increased the risks of TRM and OS were older age (51–60 years), KPS <90%, chemoresistance at transplant, and earlier transplant yr (before 2001 vs later). Older age and chemoresistance were also associated with progression and lower PFS. There were no significant interactions between graft type and other prognostic variables; in particular, relative risk of outcomes with allo vs autoHCT were similar for patients with chemosensitive and chemoresistant disease. In summary, myeloablative alloHCT increased risks of early TRM and mortaliy without an effect on progression (compared to autoHCT). Transplant type did not affect outcomes after 12 months post-transplant. AutoHCT was associated with superior survival (fig 1), and the difference was not explained by differences in chemosensitivity at the time of transplant. AutoHCT AlloHCT Outcomes (95%CI) (95%CI) AGVHD @ day 100 N/A 42 (31–53) CGVHD @ 5yrs N/A 27 (18–38) TRM @ 5yrs 18 (15–20) 45 (34–57) Relapse/progression @ 5yrs 39 (36–43) 33 (23–44) PFS @ 5yrs 43 (40–46) 26 (18–37) OS @ 5yrs 49 (46–53) 27 (18–27) Figure 1 Figure 1.

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Ethnic Disparities and Their Association With Outcomes In Chronic Myeloid Leukemia

Blood ◽

10.1182/blood.v122.21.2917.2917 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2917-2917 ◽

Cited By ~ 1

Author(s):

Sikander Ailawadhi ◽

Dongyun Yang ◽

Wendy Cozen ◽

Asher Chanan-Khan

Keyword(s):

Survival Analysis ◽

Chronic Myeloid Leukemia ◽

Ethnic Minorities ◽

Myeloid Leukemia ◽

Significant Interaction ◽

Age Groups ◽

Age At Diagnosis ◽

Investigational Product ◽

Hispanic Patients ◽

Race Ethnicity

Abstract Background Outcomes for patients with chronic myeloid leukemia (CML) have improved in recent years. Nonetheless, survival disparities persist between various patient subgroups. There have been limited reports of ethnic variations in CML outcomes, with limited data on ethnic minorities (Hispanics and Asians), who are the fastest growing ethnic subgroups in the Unites States. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of CML patients, with a specific focus on various ethnicities. Methods SEER 17 Registry data (1973-2010) was utilized. Adult (>18 years) patients with confirmed diagnosis of CML were eligible. To avoid bias of under representation by ethnic minorities, analysis was restricted to patients with a diagnosis date of 1992 or later (SEER expansion). Cases that received a diagnosis at death certificate/autopsy, no follow-up records, or lacking age at diagnosis, sex, or race/ethnicity documentation were excluded. Cox proportional hazards models, adjusted for confounding variables, were used to evaluate association between patient characteristics and overall survival (OS). All statistical tests were two-sided with a significance level of 0.05, utilizing the SAS software (v9.2). Results The final analysis included 10,356 CML patients (5,943 males; 57.4%, 4,413 females; 42.6%). Age group cohorts included: 18-44 years (2,592; 25%), 45-54 years (1,706; 16.5%), 55-64 years (1,817; 17.6%), 65-74 years (1,876; 18.1%), and ≥75 years (2,365; 22.8%). Patients were stratified by race/ethnicity: White (7,292; 70.4%), African-American (AA) (1,143; 11%), Hispanic (1,163; 11.2%), Asian (697; 6.7%), and Native American (61; 0.6%). For survival analysis, Native Americans were excluded due to their small numbers. Patients were also stratified based on year of diagnosis (1992-1999, 2000-2004 and 2005-2010) to study the impact of evolving therapeutics on CML outcomes. Median age at diagnosis was significantly different among ethnicities (p<0.001) with Hispanics the youngest (47 years) and Whites the oldest (63 years) (Figure 1). There were more Hispanic and AA CML patients reported in recent years in the database than those in 1992-1999 or 2000-2004 (p<0.001). Survival analysis revealed that for all patients, females had a significantly better median OS than males (7.8 years vs. 6.4 years; p<0.001). Among the different age cohorts, median OS got progressively worse with increasing age at diagnosis (p<0.001), with a median OS of 15+ years in 18-44 year cohort vs. 2.3 years in patients ≥75 years. Patients diagnosed more recently had a better median OS (1992-1999: 4.5 years vs. 2000-2004: 7.7 years vs. 2005-2010: 9.8 years; p<0.001). AA had the worst median OS among all ethnicities, which was significantly worse than Whites (reference) (5.8 years vs. 7.4 years; p<0.001). Asians had a median OS of 6.4 years and Hispanics 6 years. In a multivariate model using race, age at diagnosis, year of diagnosis, sex and marital status, a significant interaction was noted between year of diagnosis and race, with all racial subgroups showing improvement in 5-year survival in more recent time periods (p=0.001) (Figure 2). A significant interaction was also noted between year of diagnosis and age, with a progressive improvement in 5-year survival noted across all age groups in more recent years (p<0.001) (Figure 3). Conclusions We present a population-based study of outcomes in CML with the largest representation of ethnic minorities reported so far. We noted a higher number of AA and Hispanic patients reported to the SEER database in recent years. Hispanic patients had a significantly younger age at diagnosis, which could mean longer treatment duration over the lifetime of a patient. AA patients had the worst median OS among all ethnicities, although all ethnicities and age groups were noted to have progressive improvement in outcomes in more recent years of diagnosis. The incremental benefit in outcomes was seen most for Asians and least for Whites. These results will help in better understanding of ethnic influences on disease biology and clinical behavior as well as optimal triaging of healthcare resources. Disclosures: Off Label Use: The abstract shows scientific information on SAR245409 which is an investigational product developed by Sanofi. This investigational product is not approved by any health authority for any indication.

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Clinical and Biological Features of Primary Testicular B-Cell Lymphoma - a Single-Institution Study of 89 Cases

Blood ◽

10.1182/blood.v124.21.3036.3036 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3036-3036

Author(s):

Sanam Loghavi ◽

Zijun Yidan Xu-Monette ◽

Luis Fayad ◽

Larry W Kwak ◽

Bouthaina S. Dabaja ◽

...

Keyword(s):

Radiation Therapy ◽

B Cell ◽

Cell Lymphoma ◽

Cell Lineage ◽

B Cell Lymphoma ◽

Intrathecal Chemotherapy ◽

Stage Iii ◽

Proliferation Index ◽

Ki 67 ◽

Testicular Lymphoma

Abstract Context: Primary testicular lymphoma (PTL) is an aggressive form of extranodal lymphoma almost always of B-cell lineage. The data regarding prognostic indicators and appropriate treatment regimens in patients with PTL, especially in the era of rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone (R-CHOP) therapy are not well established. Objective: To evaluate the clinicopathologic features and their impact on outcome in patients with primary testicular lymphoma (PTL) of B-cell lineage. Patients and Design: We retrospectively analyzed the characteristics of 89 patients with PTL referred to our institution between September 1, 1998 and May 31, 2014. Follow up data was available for all patients. Detailed staging and therapy information were available for 69 and 63 patients, respectively. Cell of origin classification of DLBCL cases was determined by immunohistochemistry when possible. Results: The median age at diagnosis was 63.1 years (range, 2.9-96.2). Patients presented with stage I (26/66, 40%), stage II (14/66, 21%), stage III (4/66, 1%) and stage IV (25/66, 38%) disease, respectively. Histologic variants included: diffuse large B-cell lymphoma (DLBCL) (n=82), Burkitt lymphoma (BL) (n=2), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (n=4) and blastoid mantle cell lymphoma (n=1). Twenty-six (40%) patients had involvement of spermatic cord, epididymis and paratesticular tissues and 16 (18%) tumors showed coagulative tumor necrosis. In 31 cases DLBCL was stratified into germinal center B-cell-like (n=16, 52%) and non-germinal center B-cell-like (n=15, 42%). Six of 36 (16%) tumors analyzed showed CD5 expression by immunohistochemistry and/or flow cytometry. The median Ki-67 proliferation index was 80% in 24 cases analyzed (range, 40-100%). Four of 16 cases (25%) analyzed were positive for MYC rearrangement by fluorescence in situ hybridization. Among patients with available data (n=63); all received systemic chemotherapy (41, R-CHOP, 9 CHOP and 13 other regimens) +/- prophylactic intrathecal chemotherapy (n=48) and/or consolidation involved field radiation therapy (n=37, 23 patients with stage I/II and 12 patients with stage III/IV disease). Response to therapy was documented in 61 patients; 85% achieved complete remission, 7% partial remission and 8% had progressive disease (PD). Recurrent and/or PD were seen in 28 of 65 (43%) patients with available data. The most frequent sites of recurrence included lymph nodes (23%), soft tissues (19%), leptomeninges/brain (19%) and contralateral testicle (13%). The median overall survival (OS) and progression free survival (PFS) were 84.7 and 55.7 months, respectively. Advanced Ann Arbor stage (p=0.05, PFS), involvement of ≥2 extranodal sites (p=0.05, OS), elevated serum LDH level (p=0.013 and 0.026, OS and PFS respectively), and International Prognostic Index ≥2 (p=0.04, OS) were significantly associated with poorer outcome. Administration of prophylactic intrathecal chemotherapy (p=0.0017 and 0.012, OS and PFS, respectively) and consolidation radiation therapy (Figure 1, p=0.01 and 0.033, OS and PFS, respectively) were significantly associated with better outcome by univariate analysis. The association of consolidation radiation therapy with outcome was diminished in patients with stage III and IV disease. There was no significant association between different chemotherapy regimens and outcome, although patients who received rituximab showed a trend for better OS and PFS. Microscopic involvement of spermatic cord, epididymis and paratesticular tissue was associated coagulative necrosis (p= 0.04) and poorer outcome (p=0.018 and 0.023, OS and PFS respectively). Non-DLBCL histology type was significantly associated with nodal involvement at presentation (p=0.05). We observed a trend for shorter PFS in patients whose tumors had a Ki-67 proliferation index of ≥90% (p=0.2). There was no significant association between GCB vs. non-GCB subtypes, CD5 expression or MYC gene rearrangement and outcome. Conclusions: Our results indicate that PTL of B-cell lineage represents a distinctive group of extranodal lymphomas with unique clinical, biological and prognostic features. The data further demonstrate the beneficial therapeutic impact of prophylactic intrathecal chemotherapy and consolidation radiation therapy in patients with PTL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Comparative effectiveness of radical cystectomy versus bladder-sparing treatment for muscle-invasive urothelial carcinoma: A population-based report.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.334 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 334-334 ◽

Cited By ~ 1

Author(s):

Maxine Sun ◽

Giorgio Gandaglia ◽

Pierre I. Karakiewicz ◽

Jim C. Hu ◽

Simon P. Kim ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Radical Cystectomy ◽

Advanced Disease ◽

Population Based ◽

Disease Stage ◽

Treatment Modalities ◽

Radiation Hazard ◽

Survival Outcomes ◽

Significant Difference ◽

Muscle Invasive

334 Background: Radical cystectomy (RC) represents the standard of care for patients with muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Alternative organ-conserving treatments such as chemotherapy and/or radiotherapy have gained interest. We sought to compare survival outcomes of patients according to treatment modalities, in a stage-for-stage analysis. Methods: We relied on the Surveillance, Epidemiology, and End Results Medicare-linked database to identify 12,950 patients diagnosed with T2–T4a N0/x M0 UCUB between years 1992 and 2009. Treatment types include RC (n=5207), chemotherapy/radiation (n=2,669), and surveillance (n=5,074). Following instrumental variable analysis, Cox- and competing-risks regression analyses were performed for prediction of overall survival (OS) and cancer-specific mortality (CSM), respectively. All analyses were stratified according to disease stage (T2, T3, T4a). Results: After adjusting for potential confounders, OS was more favorable for RC relative to chemotherapy/radiation (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.02–2.40) or surveillance (HR: 1.82, 95% CI: 1.20–2.78) in patients with T2 UCUB. For the same stage, CSM rates were lower in the surgery group compared to chemotherapy/radiation (HR: 2.05, 95% CI: 1.14–3.67) or surveillance (HR: 1.95, 95% CI: 1.09–3.48). When analyses focused on individuals with more advanced disease (T3–T4a), no statistically significant difference was observed between chemotherapy/radiation relative to RC for both OS and CSM. Conclusions: In the current retrospective population-based cohort, RC was associated with improved survival outcomes relative to its alternative treatment counterparts. However, this effect was only observable in patients with T2 disease. Conversely, no difference between chemotherapy/radiation vs. surgery was noted in patients with more advanced disease stage.

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Haemophagocytic lymphohistiocytosis (HLH) in patients with large B-cell lymphoma treated with standard of care (SOC) axicabtagene ciloleucel (Axi-cel).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.8057 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 8057-8057

Author(s):

Sairah Ahmed ◽

fateeha furqan ◽

Paolo Strati ◽

Jason Westin ◽

Luis Fayad ◽

...

Keyword(s):

Cell Therapy ◽

Organ Failure ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

Disease Stage ◽

High Dose ◽

Multi Organ Failure ◽

Significant Difference ◽

Experienced Grade

8057 Background: HLH is a rare but serious complication of chimeric antigen receptor (CAR) T cell therapy, characterized by severe immune activation, and immune mediated multi-organ failure. Diagnosis is difficult in the context of cytokine release syndrome (CRS) and optimal treatment and outcomes are unclear. Methods: Retrospective, descriptive analysis of patients with relapsed/refractory LBCL treated with SOC axi-cel at MD Anderson Cancer Center between 01/2018 - 10/2019 (data cut-off 12/21/2019). Progression-free survival (PFS) defined as time from axi-cel infusion to progression/death or last follow-up. Diagnosis of HLH per HLH-2004 and CART cell therapy toxicity guidelines (Neelapu, 2018) Results: One hundred and five patients with relapsed/refractory LBCL included, 6 diagnosed with HLH. No significant difference in baseline characteristics, disease stage, international prognostic index or inflammatory markers at baseline between groups, with exception of platelet count which was lower in HLH group 116 [37-129] versus 141 [9-391] (p = 0.07). Development of HLH was early after CART cell infusion at a median 11 days [7 – 78 days] with 3 patients having bone marrow hemophagocytosis; all 6 had abnormalities in liver function tests, fibrinogen, triglycerides, and at least 1 ferritin level > 10,000. CART toxicity in HLH cohort: 4 patients experienced grade 0-1 CRS, and 1 with grade 2 CRS while 3 HLH patients experienced grade 3-4 IEC-associated neurotoxicity syndrome ( ICANS), and 2 patients had grade 0-1 ICANS. Five HLH patients treated with high dose steroids, and tocilizumab; anakinra administered in 2 patients. Four of 6 patients had resolution of HLH with treatment and didn’t require escalation to HLH specific therapy however 1 patient was treated with steroids/etoposide. PFS and overall survival (OS) were significantly shorter in HLH group, PFS 1 months vs 8 months, respectively (p < 0.001) and median OS 2 months vs not reached, respectively (p = 0.001) follow up 10 months (95% CI 8-12 months). One patient died of acute respiratory failure, 2 patients died of HLH and multi-organ failure without progressive disease (PD). Of 3 remaining patients, all had radiographic PD at day 30, 2 of whom died of PD. Conclusions: HLH is likely an underreported complication of CART cell therapy, and patients with HLH have significantly worse outcomes. In this series the majority of patients died of PD, not the syndrome itself. More information is necessary to design treatment strategies that won’t compromise CART outcomes.

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Survival and Transformation of Marginal Zone Lymphoma: A Finnish Nationwide Population-Based Study

Blood ◽

10.1182/blood-2021-149764 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4517-4517

Author(s):

Ilja Kalashnikov ◽

Tomas Tanskanen ◽

Leevi Viisanen ◽

Nea Malila ◽

Sirkku Jyrkkio ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Cumulative Risk ◽

B Cell Lymphoma ◽

Population Based ◽

Age At Diagnosis ◽

Large B Cell Lymphoma ◽

Crude Mortality Rate ◽

Large B Cell

Abstract Background Marginal zone lymphoma (MZL) is an indolent B-cell lymphoma with classical histopathological lesions and heterogeneous anatomical and clinical features. It is divided into three subtypes depending on the site of lymphoma involvement with extranodal MZL of mucosa-associated lymphoid tissue (MALT, ∼70%) being the most common, followed by splenic (SMZL, ∼20%) and nodal subtypes (NMZL, <10%). Although these subtypes differ with regard to biology and clinical presentation, MZLs are generally associated with long survival. However, a proportion of MZLs undergo transformation to large B-cell lymphoma characterized by aggressive clinical behavior and increased mortality. Population-based long-term data on transformation of MZL is lacking. Aims We estimated overall survival and the risk of transformation to large B-cell lymphoma in patients diagnosed with MZL in Finland in 1995−2018. We also compared mortality rates between the patients with or without transformation. Methods Patients diagnosed with incident MZL (ICD-O-3 morphology codes 9689/3 and 9699/3) and lymphoma not otherwise specified (NOS) (9590/3, 9591/3) in Finland between 1995 and 2018 were retrieved from the Finnish Cancer Registry (FCR). The Registry has an excellent coverage and provides accurate population-based nationwide data for all histologically verified cancers in Finland. The diagnosis of MZL and possible transformation were confirmed from the pathology reports. Transformation was defined as the diagnosis of morphologically verified large B-cell lymphoma at least 3 months after the primary diagnosis of MZL. For all patients with histologically verified MZL, we collected data on subtype, gender, date of birth, MZL diagnosis and last follow-up (f-up), vital status at the end of f-up, and date of transformation. F-up for overall survival (OS) was completed on December 31, 2018. The patients with missing information regarding MZL subtype or incorrect diagnostic were excluded. No patients were lost to f-up before the end of the study period, and none of the MZL diagnoses nor transformations were recorded by death certificate or autopsy only. The start of the f-up was defined as the date of MZL diagnosis. OS and the cumulative risk of transformation were estimated by the Kaplan-Meier method. Analysis of total mortality was performed using Cox regression. Risk factors included age at diagnosis, year of diagnosis, gender, and MZL subtype. Transformation was treated as a time-varying covariate. All statistical analyses were performed using R, version 4.0.4. Results We identified 1341 patients diagnosed with MZL after above mentioned exclusions. Baseline characteristics, as well as subtype-specific rates of transformation and death, are shown in the Table 1. Median age at diagnosis was 68 years (IQR, 58−76; range, 13−95 years), with a slight female predominance (59%). MALT subtype was the most frequent, followed by SMZL and NMZL. There were no clinically significant differences in age at diagnosis between males and females nor in the MZL subtypes. Median follow-up time was 5.5 years (IQR, 2.1−10.5; range 0−24 years). The majority of the NMLZ patients were diagnosed during more recent years. Transformation occurred in 47 patients during 9315 person-years of follow-up (crude transformation rate, 5.0 per 1000). The cumulative risk of transformation was 2.8% (95% CI, 1.7-3.8) at 5 years and 5.6% (95% CI, 3.8-7.3) at 10 years from diagnosis (Fig. 1), with no apparent plateau. Overall, 519 (39%) patients died during a total f-up of 9435 person-years (crude mortality rate, 55.0 per 1000). In comparison, the crude mortality rate following transformation was 233.4 per 1000. OS was 66.2% (95% CI, 73.8−78.7) at 5 years and 58.9% (95% CI, 55.8−62.2) at 10 years from diagnosis (Fig. 2). After adjusting for potential confounders (age at diagnosis, gender, year of diagnosis, and MZL subtype), transformation was associated with a substantial increase in mortality (HR, 5.13; 95% CI, 3.47−7.59; p < 0.001) (Table 2). Conclusions In this large nationwide population-based study, the risk of transformation to large B-cell lymphoma was 5.6% at 10 years, and transformation was associated with a substantially increased risk of death. Long-term OS and baseline characteristics were in accordance with previously published data for MZL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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