Patterns of Care and Predictors of Survival in Adolescents and Young Adults with Hodgkin Lymphoma: A Population-Based Study

Introduction: Hodgkin lymphoma (HL) is one of the most treatable cancers affecting adolescent and young adult (AYA) patients (15 - 39 years), however optimal therapy for de novo disease in this population remains a subject of debate. Population-based studies in HL consistently report a survival disadvantage for AYAs when compared with younger patients. Though the etiology of these disparities is unclear, analyses of clinical trials data suggest that observed survival differences may relate to treatment, rather than to age. Because registry analyses are often limited by lack of information about clinical characteristics and therapeutic exposures, the independent effect of age on HL-outcome outside of the cooperative group setting is unknown. To address this gap in the literature, we: (1) examined initial treatment regimen and patterns of care in a population-based cohort of AYAs compared to children with de novo HL, and (2) examined the impact of sociodemographic and clinical variables on overall survival (OS) and disease-specific survival (DSS) by age, after adjusting for therapy. Methods: Data for 4,426 patients aged 0 - 39 years diagnosed with classical HL between 2007 and 2016 were obtained from the California Cancer Registry (CCR). Detailed treatment information for each patient was extracted from unstructured free-text fields in the CCR database. Chemotherapy regimens were classified based on standard treatment approaches for adult and pediatric HL (Table). Multivariable cox proportional hazards regression models were used to examine the influence of sociodemographic and clinical variables on OS and DSS, overall and by age group, and are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Models were adjusted for race/ethnicity, sex, insurance, neighborhood socioeconomic status, histology, stage, B symptoms, treatment location at a NCI (National Cancer Institute)-designated cancer center, and radiation therapy (RT). Results: Of the 4,426 patients in this cohort, 33% were <21 years (y) (N= 1,479) and 67% were 22 - 39y (N= 2,947). At median follow-up of 4.4 years, 3-year OS in the full cohort was 95%. Front-line therapy for patients with HL differed significantly across age groups (Table). Approximately 42% of patients <21y received ABVD vs. 69% of older patients. Compared with older patients, a higher proportion of younger patients received ABVE-PC (younger: 8.8% vs. <1%) and modified treatment regimens (younger: 24% vs. 9.6%). Regimens were considered modified if they omitted one drug from a standard protocol but were otherwise administered according to expected dosing schedules; the most common were ABV (18%) and AVD (15%). A higher proportion of patients with private (vs. public/no) insurance received STANFORD V chemotherapy. In total, 40% of patients aged <21y received RT as part of initial therapy vs. 27% of patients 22 - 39y. In survival models, increasing age was associated with a higher risk of death. Compared with patients <14y, the hazard of death from HL was over three-fold higher in patients 22 - 29y (aHR=3.1, CI: 1.1, 9.1) and 30 - 39y (aHR=3.8, CI: 1.3, 11.2). In multivariable models stratified by age, race/ethnicity, insurance, B-symptoms and stage were each significantly associated with survival. In patients <21y, NHBs (aHR: 7.1, CI: 2.4, 20.6) and Hispanics (aHR: 2.5, CI: 1.0, 6.4) experienced worse DSS than NHWs. Having public or no insurance also conferred worse OS (aHR: 1.9, CI: 1.1, 3.5), but initial therapy did not significantly impact OS or DSS. Among those aged 22 - 39y, NHB patients had worse OS (aHR: 1.7, CI: 1.0, 2.8) as did patients with public or no insurance (aHR: 1.7, CI: 1.2, 2.3). Stage IV disease was associated with inferior OS (aHR: 2.9, CI: 1.3, 6.8) and DSS (aHR: 3.3, CI: 1.1, 9.6). Finally, modified treatment regimens (vs. ABVD) were associated with worse OS (aHR: 1.6, CI: 1.0, 2.5), but did not significantly impact DSS in AYAs. Conclusion: In this large, population-based cohort of children and AYAs with HL, we observed that initial therapy varies, but that the majority of AYAs receive ABVD. Variation in therapy was largely insufficient to explain observed survival disparities, as older age, NHB and Hispanic race/ethnicity, and public or no insurance each conferred increased risk of death, even after adjustment for chemotherapy regimen. Further analyses examining comorbidities, treatment-related toxicities, and cause of death are ongoing. Disclosures No relevant conflicts of interest to declare.

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Excessive Early Mortality Drives Poor Long Term Outcomes Among Older Patients With Classical Hodgkin Lymphoma: A Population Study

Blood ◽

10.1182/blood.v122.21.1742.1742 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1742-1742

Author(s):

Luciano J. Costa

Keyword(s):

Hodgkin Lymphoma ◽

Older Patients ◽

Conflicts Of Interest ◽

Age At Diagnosis ◽

Classical Hodgkin Lymphoma ◽

Nodal Disease ◽

Early Stage Disease ◽

Younger Patients ◽

Risk Of Death ◽

One Year

Background Classical Hodgkin Lymphoma (cHL) is a highly curable malignancy in young adults. Most of the information available on natural history and management of cHL comes from series and clinical trials in young patients. There is limited information on the outcomes of older patients with cHL Methods We analyzed the characteristics and outcomes of a large contemporary cohort of cHL patients ≥ 65 years diagnosed in the US and reported to the Surveillance Epidemiology and End Results program (SEER-18). Inclusion criteria consisted of diagnosis of cHL as first malignant neoplasm, year of diagnosis 2000-2010, known stage and known race. Cases reported from death certificate or autopsy only were excluded. Information retrieved contained age at diagnosis, year of diagnosis, race, sex, histological subtype, stage, presence of extra-nodal disease and survival time. Characteristics of cHL in patients ≥ 65 years (older) were compared to those < 65 years (younger). We subsequently estimated relative survival (RS) for different stages and age strata among older patients comparing with outcomes in younger patients. Results There were 20815 cases of cHL reported during the period with median follow up of 48 months, including 2884 (13.8%) cases in older patients. Older patients were more likely to present with extra-nodal disease (4.7% vs. 2.2%, P< 0.001), advanced stage (52.6% vs. 37.3%, P<0.001) and with lymphocyte depleted cHL (3.3% vs. 0.9%) or mixed cellularity cHL (22.5% vs. 11.3%, P<0.001) than younger patients. Additionally, older cHL patients with early stage disease were less likely to receive radiation therapy (35.6% vs. 48.2%, P<0.001). RS at one year (64% vs. 95.7%, P<001) and 5-years (49% vs. 89%, P<0.001) was much inferior in older than in younger patients, even when stratified by early (I and II) and advanced (III and IV) stages (Figure). RS deteriorated quickly with increasing age at diagnosis. One year RS was 73.9%, 56.3% and 43.3% and 5-years RS was 57.9%, 41.6% and 30.4% for patients 65-74, 75-84 and 85+ years, respectively. Even with adjustment for histology, sex, year of diagnosis and race, patients 65-74 years (HR = 4.81, 95%CI 4.41-5.26, P<0.001) 75-84 years (HR = 9.60, 95% CI 8.78-10.49, P<0.001) and 85+ years (HR = 16.19, 95% CI 14.15-18.51, P<0.001) were at a much higher risk of death than younger cHL patients. Conclusion cHL has distinct presentation and far worse prognosis in older patients with excessive early (<1 year) mortality. There is a need to further understand patterns of treatment failure and develop age-specific therapeutic interventions for this group. Disclosures: No relevant conflicts of interest to declare.

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Survival by Race and Ethnicity in Pediatric and Adolescent Patients With Hodgkin Lymphoma: A Children’s Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.19.00812 ◽

2019 ◽

Vol 37 (32) ◽

pp. 3009-3017 ◽

Cited By ~ 2

Author(s):

Justine M. Kahn ◽

Kara M. Kelly ◽

Qinglin Pei ◽

Rizvan Bush ◽

Debra L. Friedman ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Race And Ethnicity ◽

Proportional Hazards ◽

De Novo ◽

Combined Modality Therapy ◽

Population Based ◽

Cox Proportional Hazards ◽

Phase Iii ◽

Oncology Group ◽

Race Ethnicity

PURPOSE Population-based studies of children and adolescents with Hodgkin lymphoma (HL) report a survival disadvantage in nonwhite—non-Hispanic black (NHB) and Hispanic—patients. Whether disparities persist after adjustment for clinical and treatment-related variables is unknown. We examined survival by race/ethnicity in children receiving risk-based, response-adapted, combined-modality therapy for HL in contemporary Children’s Oncology Group trials. PATIENTS AND METHODS This pooled analysis used individual-level data from 1,605 patients (younger than age 1 to 21 years) enrolled in phase III trials for low-risk (AHOD0431), intermediate-risk (AHOD0031), and high-risk (AHOD0831) HL from 2002 to 2012. Event-free survival (EFS) and overall survival (OS) were compared between non-Hispanic white (NHW) and nonwhite patients. Cox proportional hazards for survival were estimated for both de novo and relapsed HL, adjusting for demographics, disease characteristics, and therapy. RESULTS At median follow up of 6.9 years, cumulative incidence of relapse was 17%. Unadjusted 5-year EFS and OS were 83% (SE, 1.2%) and 97% (SE, < 1%), respectively. Neither differed by race/ethnicity. In multivariable analyses for OS, nonwhite patients had a 1.88× higher hazard of death (95% CI, 1.1 to 3.3). Five-year postrelapse survival probabilities by race were as follows: NHW, 90%; NHB, 66%; and Hispanic, 80% ( P < .01). Compared with NHW, Hispanic and NHB children had 2.7-fold (95% CI, 1.2 to 6.2) and 3.5-fold (95% CI, 1.5 to 8.2) higher hazard of postrelapse mortality, respectively. CONCLUSION In patients who were treated for de novo HL in contemporary Children’s Oncology Group trials, EFS did not differ by race/ethnicity; however, adjusted OS was significantly worse in nonwhite patients, a finding driven by increased postrelapse mortality in this population. Additional studies examining treatment and survival disparities after relapse are warranted.

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Patterns of Care and Outcomes Among Older Patients with Myelofibrosis: A Population-Based Study

Blood ◽

10.1182/blood-2020-137543 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 21-22

Author(s):

Shelby Meckstroth ◽

Rong Wang ◽

Xiaomei Ma ◽

Nikolai A. Podoltsev

Keyword(s):

Median Survival ◽

Research Funding ◽

Multivariable Analysis ◽

Population Based ◽

Janus Kinase ◽

Patterns Of Care ◽

Age At Diagnosis ◽

Jak Inhibitor ◽

Risk Of Death

Background: Myelofibrosis (MF) is a Philadelphia chromosome negative myeloproliferative neoplasm associated with systemic and splenomegaly-related symptoms, cytopenias and decreased survival. Approval of ruxolitinib, an oral janus kinase (JAK)-inhibitor, for higher-risk MF patients (pts) by the Food and Drug Administration in 11/ 2011 opened a new era of targeted treatment for this disease. There are limited data on the "real-world" clinical experiences and outcomes of pts with MF treated in the JAK inhibitor era. MF became reportable to population-based cancer registries including the Surveillance, Epidemiology and End Results (SEER) program in 2001, making its investigation possible at the population level. The objective of this study was to assess the patterns of care and outcomes of older MF pts in the ruxolitinib era. Methods: Using the linked SEER-Medicare database, we identified a cohort of older pts diagnosed with MF from 2007 through 2015 who fulfilled the following eligibility criteria: 1) aged 66-99 years at diagnosis; 2) had known month of diagnosis; 3) were not identified from death certificate or autopsy only; 4) had continuous enrollment in Medicare Parts A, B and no enrollment in health maintenance organizations from 1 year before diagnosis until the end of follow-up (death or 12/31/2016, whichever came first); 5) had continuous enrollment in Medicare Part D from diagnosis until the end of follow-up; and 6) bone marrow biopsy claim from 1 year before diagnosis to end of follow up. Treatments were assessed via Medicare parts B&D claims. Kaplan-Meier curves and log-rank tests were used to compare survival between patient groups. Multivariable cox proportional hazards regression models were used to assess the effect of ruxolitinib use on survival in MF pts. Aside from treatment, we considered the influence of several characteristics on survival, including age at diagnosis, sex, race/ethnicity, marital status, comorbidities, SEER region and percentage living in poverty at the census tract level. Results: Among 528 MF pts, median age at diagnosis was 76 (interquartile range [IQR], 71- 80) years with 88.8% white and 56.1% male. 230 pts were diagnosed in the early era (2007-2011), and 298 in the late era (2012-2015), of which 113 (37.9%) were ruxolitinib users. There was no difference among any evaluated characteristics between two eras and by ruxolitinib status in the late era. The median duration of ruxolitinib use was 11.9 months. Similar number of pts started at 5, 10, 15 and 20 mg twice a day (BID) (Figure 1). Among 31 pts who started at ≤5 mg BID, 15 (48.4%) never had their dose of ruxolitinib escalated. While on ruxolitinib treatment, nearly half of the pts received additional medications for symptom management including hydroxyurea (22.6%), prednisone (17.9%) or both (10.4%). < 11 users were able to go up to the highest dose of 25 mg BID. Ruxolitinib was interrupted > 30 days for 31 times by 20 of 113 (17.7%) pts with median interruption duration of 43 (IQR 34-71) days. The median survival was 2.70 (95% confidence interval [CI]: 1.87-3.41) years and 2.62 (95% CI: 2.15-3.07) for the early and late era pts, respectively (p for log-rank 0.91). The multivariable analysis showed no impact of diagnosis era on survival (late vs early era hazard ratio (HR) of 1.08, 95% CI 0.83-1.40; p= 0.57). There was no difference in survival by ruxolitinib status (log-rank test, p=0.31), with a median survival of 2.76 (95% CI: 2.01-4.15) years and 2.53 (95% CI: 1.92-3.07) years among users and non-users, respectively (Figure 3). In the multivariable analysis, the risk of death among ruxolitinib users compared to non-users was not statistically significant with HR of 0.82 (95% CI 0. 59-1.16; p= 0.26). Conclusions: Older MF pts treated with ruxolitinib had similar survival when compared to pts who did not receive this medication, but the choice of ruxolitinib might have been influenced by disease risk which we were unable to assess. For many ruxolitinib users, the drug was interrupted, the dose was not escalated, additional medications were used concurrently (possibly to help control disease manifestation), and treatment was discontinued quickly after initiation. Optimization of ruxolitinib use may be necessary to accomplish better outcomes. Furthermore, development of new drugs which may be used together with ruxolitinib or after its discontinuation is needed. The work was supported by The Frederick A. Deluca Foundation. Disclosures Wang: Celgene/BMS: Research Funding. Ma:Celgene/BMS: Research Funding; BMS: Consultancy. Podoltsev:Jazz Pharmaceuticals: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria; Sunesis Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria; Bristol-Myers Squib: Consultancy, Honoraria; Genentech: Research Funding; AI Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Astellas Pharma: Research Funding; Kartos Therapeutics: Research Funding; CTI biopharma: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Astex Pharmaceuticals: Research Funding; Daiichi Sankyo: Research Funding; Arog Pharmaceuticals: Research Funding.

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Patterns of Care in Palliative Radiotherapy: A Population-Based Study

Journal of Oncology Practice ◽

10.1200/jop.2012.000835 ◽

2013 ◽

Vol 9 (5) ◽

pp. e220-e227 ◽

Cited By ~ 56

Author(s):

James D. Murphy ◽

Lorene M. Nelson ◽

Daniel T. Chang ◽

Loren K. Mell ◽

Quynh-Thu Le

Keyword(s):

Palliative Radiotherapy ◽

Population Based ◽

Patterns Of Care ◽

Population Based Study ◽

Underlying Causes ◽

Race Ethnicity ◽

Improve Access

Inequality in the receipt of palliative radiotherapy exists on the basis of age, comorbidity, and race/ethnicity. Further research into the underlying causes of these discrepancies will improve access to palliative irradiation.

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Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study

Blood ◽

10.1182/blood-2004-09-3759 ◽

2005 ◽

Vol 106 (7) ◽

pp. 2444-2451 ◽

Cited By ~ 134

Author(s):

Ruth F. Jarrett ◽

Gail L. Stark ◽

Jo White ◽

Brian Angus ◽

Freda E. Alexander ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Older Patients ◽

Epstein Barr Virus ◽

Statistical Significance ◽

Survival Rates ◽

Population Based ◽

Population Based Study ◽

Barr Virus ◽

Epstein Barr ◽

The Impact

AbstractThe association between tumor Epstein-Barr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBV-negative compared with EBV-positive patients (P < .001), with 5-year survival rates of 81% and 66%, respectively; disease-specific survival (DSS) was also greater for EBV-negative patients (P = .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P = .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P = .003). Excess deaths occurred in EBV-positive patients with both early- and advanced-stage disease. In multivariate analysis of OS in the older patients, EBV status retained statistical significance after adjusting for the effects of sex, stage, and B symptoms (P = .01). Impaired immune status may contribute to the development of EBV-positive cHL in older patients, and strategies aimed at boosting the immune response should be investigated in the treatment of these patients. (Blood. 2005;106:2444-2451)

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Abstract 14948: Comparative Effectiveness of CRT in Older Patients With Heart Failure: Systematic Review and Meta-Analysis

Circulation ◽

10.1161/circ.142.suppl_3.14948 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Saeed Juggan ◽

Clifford A Reilly ◽

Praveen K Ponnamreddy ◽

Lauren Gilstrap ◽

Emily Zeitler

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Comparative Effectiveness ◽

Older Patients ◽

Meta Analysis ◽

Cardiac Resynchronization ◽

Cochrane Library ◽

Complication Rates ◽

Younger Patients ◽

Risk Of Death

Background: The pivotal cardiac resynchronization therapy (CRT) trials enrolled patients significantly younger than the typical contemporary heart failure with reduced ejection fraction (HFrEF) patients. Benefits of CRT in older HFrEF patients is largely unknown and may be less due to higher comorbidity burdens and higher procedural risk. We sought to address this evidentiary gap through meta-analysis. Hypothesis: Compared to patients <70 years old (”younger”), patients ≥ 70 years old (“older”) have similar mortality rates, rates of complications and changes in ejection fraction (EF) following CRT. Methods: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older HFrEF patients. Differences in mortality and mean difference (MD) in EF were calculated between groups. Random effects meta-analysis of MD in EF (older minus younger) and relative risk (RR) of death and complications are reported along with estimates of heterogeneity. Results: Seven studies [n= 4381 younger, 1203 older] were included in LVEF meta-analysis. Compared to younger patients, there was greater EF improvement in older patients [MD 1.20; 95% CI 0.13 - 2.28, p=0.03, I 2 =46%]. RR of mortality was analyzed for 11 studies [n=5038 younger, 1653 older] (Figure). Survival was better in younger patients [RR 1.06; 95% CI 1.04 - 1.09, p<0.01, I 2 =0%]. No significant differences in complication rates were observed between younger and older patients. Conclusions: CRT in older patients was associated with greater improvement in EF than younger patients. Mortality is greater in older patients which may reflect greater underlying risk of death from competing causes. Figures:

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Trends in Overall Survival and Treatment Patterns in Two Large Population-Based Cohorts of Patients with Breast and Colorectal Cancer

Cancers ◽

10.3390/cancers11091239 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1239 ◽

Cited By ~ 1

Author(s):

Abbema ◽

Vissers ◽

Vos-Geelen ◽

Lemmens ◽

Janssen-Heijnen ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Survival Rates ◽

Relative Survival ◽

Population Based ◽

Treatment Patterns ◽

Entire Study ◽

Younger Patients ◽

Risk Of Death ◽

Over Time

Previous studies showed substantial improvement of survival rates in patients with cancer in the last two decades. However, lower survival rates have been reported for older patients compared to younger patients. In this population-based study, we analyzed treatment patterns and the survival of patients with breast cancer (BC) and colorectal cancer (CRC). Patients with stages I–III BC and CRC and diagnosed between 2003 and 2012 were selected from the Netherlands Cancer Registry (NCR). Trends in treatment modalities were evaluated with the Cochran-Armitage trend test. Trends in five-year overall survival were calculated with the Cox hazard regression model. The Ederer II method was used to calculate the five-year relative survival. The relative excess risk of death (RER) was estimated using a multivariate generalized linear model. During the study period, 98% of BC patients aged <75 years underwent surgery, whereas for patients ≥75 years, rates were 79.3% in 2003 and 66.7% in 2012 (p < 0.001). Most CRC patients underwent surgery irrespective of age or time period, although patients with rectal cancer aged ≥75 years received less surgery or radiotherapy over the entire study period than younger patients. The administration of adjuvant chemotherapy increased over time for CRC and BC patients, except for BC patients aged ≥75 years. The five-year relative survival improved only in younger BC patients (adjusted RER 0.95–0.96 per year), and was lower for older BC patients (adjusted RER 1.00, 95% Confidence Interval (CI) 0.98–1.02, and RER 1.00; 95% CI 0.98–1.01 per year for 65–74 years and ≥75 years, respectively). For CRC patients, the five-year relative survival improved over time for all ages (adjusted RER on average was 0.95 per year). In conclusion, the observed survival trends in BC and CRC patients suggest advances in cancer treatment, but with striking differences in survival between older and younger patients, particularly for BC patients.

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Myelodysplastic Syndromes

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2008.0069 ◽

2008 ◽

Vol 6 (9) ◽

pp. 902 ◽

Cited By ~ 13

Author(s):

_ _

Keyword(s):

Myelodysplastic Syndromes ◽

Older Patients ◽

Myeloid Leukemia ◽

De Novo ◽

Initial Therapy ◽

De Novo Aml ◽

Relative Inability ◽

Patients Experience ◽

Recent Version ◽

Clinical Problems

Myelodysplastic syndromes (MDS) represent myeloid clonal hemopathies with relatively heterogeneous spectrums of presentation. The major clinical problems in these disorders are morbidities caused by patients' cytopenias and the potential for MDS to evolve into acute myeloid leukemia (AML). Managing MDS is complicated by the generally advanced age of patients, attendant non-hematologic comorbidities, and older patients' relative inability to tolerate some therapies. In addition, when the illness progresses into AML, these patients experience lower response rates to standard therapy than patients with de novo AML. Important changes from the 2008 version of the guidelines include the addition of lenalidomide as a possible treatment for symptomatically anemic non-del(5q) patients whose anemia does not respond to initial therapy. For the most recent version of the guidelines, please visit NCCN.org

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Survival Varies By Age and Histology in Classical Hodgkin Lymphoma: A Report from the Children's Oncology Group

Blood ◽

10.1182/blood-2020-138796 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 24-25

Author(s):

Justine M. Kahn ◽

Kara M. Kelly ◽

Qinglin Pei ◽

Yue Wu ◽

Debra L. Friedman ◽

...

Keyword(s):

Clinical Trials ◽

Hodgkin Lymphoma ◽

Cumulative Incidence ◽

De Novo ◽

Oncology Group ◽

Bulky Disease ◽

Risk Of Death ◽

Increased Risk ◽

Multivariable Models ◽

Effect Of Age

Introduction While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 - 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children's Oncology Group (COG) trials. Methods This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group (<15 y vs. ≥15 y) in the pooled cohort, and in histologic subgroups (MC and non-MC) using the Kaplan-Meier method. Effect modification was confirmed between age and histology. Cox proportional hazards regression models were used to examine the influence of age on EFS and OS, adjusted for race/ethnicity, Ann Arbor stage, B symptoms, bulky disease, receipt of radiation therapy (RT), and the interaction between age and histology; COG study was also included in the model, given that the criteria for response adaptation differed across the trials. Results Between 2002 and 2012, N= 2155 patients 1 - 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) <15 y and N= 1,036 (54%) ≥15 y. In total, N= 1,547 patients (81%) had NS histology, N= 108 (6%) had cHL, NOS, and N= 196 (10%) had MC histology; by age, MC histology was present in N= 66 patients (7%) ≥15 y and N= 130 patients (15%) <15 y (p< 0.01). A significantly higher proportion of those ≥15 y vs. younger had B-symptoms at diagnosis (29% vs. 21%, p< 0.01), however the presence of bulky disease did not differ by age. Finally, patients ≥15 y (vs. <15 y) were significantly more likely to receive RT as part of their treatment (72% vs. 63%, p<0.01). Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. <15 y (85% vs 89%, p<0.01), as was the 5-year OS (96% vs. 99%, p< 0.01). In multivariable models, age ≥15 y (vs. younger) was associated with a 1.4-fold increased risk of EFS (HR: 1.4, 95% CI: 1.1, 1.8, p< 0.01), and more than a 3-fold increased risk of death (OS: HR: 3.1, 95% CI: 1.5, 6.4, p< 0.01). The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 - 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p< 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p< 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p< 0.01) (Table). Conclusion In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults. Disclosures No relevant conflicts of interest to declare.

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Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study

Blood Cancer Journal ◽

10.1038/s41408-021-00586-1 ◽

2021 ◽

Vol 11 (12) ◽

Author(s):

Ilja Kalashnikov ◽

Tomas Tanskanen ◽

Janne Pitkäniemi ◽

Nea Malila ◽

Sirkku Jyrkkiö ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Relative Survival ◽

B Cell Lymphoma ◽

Population Based ◽

Population Based Study ◽

Entire Study ◽

Risk Of Death ◽

Increased Risk ◽

Histological Transformation

AbstractNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49−16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.

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