Second malignancies and cardiovascular diseases in long-term Hodgkin lymphoma survivors: The Istituto Nazionale Tumori of Milan (INT) experience

Abstract Abstract 536 Long-term outcomes following novel therapies for CLL have rarely been reported. Between 10/90 and 12/94, 509 eligible, untreated patients (pts) with symptomatic CLL were enrolled by 4 cooperative groups onto study C9011; 179 were randomized to F, 193 to C, and 137 to F+C. After slightly more than 5 years median follow up, with the time of last follow-up in June 1999, we reported in 2000 (NEJM 343:1750) that F provided significantly higher response rates and longer remission duration and progression-free survival (PFS) than C (p<0.001 for all 3 endpoints). The combination arm with F+C was stopped early because of high morbidity and mortality. There was no difference in overall survival (OS) among the 3 groups. Nearly 10 years have now elapsed since this report. Therefore, with the time of last follow-up in January 2009, we analyzed the long term outcomes of pts enrolled on the study. PFS was defined as the time between randomization and the occurrence of progressive disease or death due to any cause. Results: Of the 509 pts, 85% have now died; among pts on the F and C arms, 92% have progressed. We found that F treatment resulted in significantly longer PFS than did C (p < 0.001), with notable differences in PFS at 2, 3, and 4 years (Table). While the F and C arms had the same OS during the initial 5 years following randomization, our current analysis with longer follow-up shows that pts treated on the F arm had better survival than did those on the C arm during the ensuing years (Figure). The p-values for this difference are 0.04 (unadjusted for covariates) and 0.07 (covariate-adjusted). The emergence of improved survival following initial F treatment, appearing only after 5-6 years, is an unexpected and noteworthy finding. Reporting second malignancies was required on this study. There were 27 epithelial cancers reported (9 on F, 11 on C, 7 on F+C), involving colon, lung, breast, prostate, pancreas, liver, bladder and skin (6 squamous, 2 melanoma). Seven therapy-related myeloid neoplasms (t-MN) were reported; 6 were on F+C; 1 on F. Richter's transformation to non-Hodgkin lymphoma was reported in 34 pts; prolymphocytic leukemia occurred in 10; Hodgkin lymphoma in 6; myeloma in 2; hairy cell leukemia in 1. These cases were distributed with 18 on F, 18 on C, and 17 on F+C. Thus, the overall incidence of second malignancies reported was 17%. Conclusion: Initial treatment with F provides better long-term outcomes than initial treatment with C. Second malignancies are common, but the overall incidence is not increased on the F-containing treatment arms except for t-MN. Disclosures: No relevant conflicts of interest to declare.

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Long-Term Results of the HD2000 Trial Comparing ABVD Versus BEACOPP Versus COPP-EBV-CAD in Untreated Patients With Advanced Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi

Journal of Clinical Oncology ◽

10.1200/jco.2015.62.4817 ◽

2016 ◽

Vol 34 (11) ◽

pp. 1175-1181 ◽

Cited By ~ 61

Author(s):

Francesco Merli ◽

Stefano Luminari ◽

Paolo G. Gobbi ◽

Nicola Cascavilla ◽

Caterina Mammi ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cumulative Risk ◽

Progression Free Survival ◽

Long Term Results ◽

Entire Group ◽

Second Malignancies ◽

Free Survival ◽

Post Hoc

Purpose The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. Patients and Methods Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). Results The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). Conclusion With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

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Analysis of long-term outcome and late toxicity in Hodgkin lymphoma survivors

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.19537 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 19537-19537

Author(s):

I. Cedrych ◽

A. Polakiewicz-Gilowska ◽

E. Nowara ◽

A. Deptala

Keyword(s):

Hodgkin Lymphoma ◽

Late Toxicity ◽

Term Outcome ◽

Long Term Outcome ◽

Lymphoma Survivors

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Cardiovascular screening in long-term Hodgkin lymphoma survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.e20592 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. e20592-e20592

Author(s):

Benjamin Reed Griffin ◽

Carrie A. Thompson ◽

Thomas Matthew Habermann ◽

Thomas E. Witzig ◽

Kay Ristow ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cardiovascular Screening ◽

Lymphoma Survivors

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Use of recommended post-treatment services for adolescent and young adult Hodgkin lymphoma survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.3_suppl.107 ◽

2016 ◽

Vol 34 (3_suppl) ◽

pp. 107-107

Author(s):

Erin Elizabeth Hahn ◽

Yi-Lin Wu ◽

Jazmine Garcia Delgadillo ◽

Corrine E. Munoz-Plaza

Keyword(s):

Young Adult ◽

Hodgkin Lymphoma ◽

Post Treatment ◽

Adolescent And Young Adult ◽

First Year ◽

Recommended Care ◽

Treatment Services ◽

Recommended Services ◽

Lymphoma Survivors

107 Background: Adolescent and young adult (AYA) Hodgkin lymphoma survivors are at high risk for long-term and late effects. Post-treatment guidelines are available from the National Comprehensive Cancer Network (NCCN) and others; however, adherence to these guidelines is unknown. The purpose of this study was to identify AYA Hodgkin survivors from an integrated health care system and examine use of post-treatment services. Methods: We identified patients diagnosed between 2000 and 2010, ages 15 to 39. We identified use of NCCN recommended services (oncology visits, labs, CT) and non-recommended services (PET scan, CT after first year). Multivariate logistic regression was used to identify associations between receipt of recommended services within first 12 months post-treatment (oncology visits, labs, CT) and patient (gender, race/ethnicity) and cancer characteristics (stage, diagnosis age, diagnosis year). Results: We identified 354 patients (see table). Almost all had recommended oncology visits within the first 5 years (96%); 70% received recommended labs. Two-thirds received a recommended CT scan within 12 months post- treatment. However, 47% received a non-recommended CT in year 2 and 35% in year 3, and 33% received a non-recommended PETs. Overall, 48% received all recommended care within the first 12 months. Diagnosis year was significant in regression, with those diagnosed 2000-2005 less likely to receive recommended care than those diagnosed 2006-2010 (OR = 0.007, p < .0001). Conclusions: Less than half of patients received recommended care within the first year post-treatment. These results will inform development of effective programs to meet survivors’ needs. Next steps include exploring risk-stratified patterns of care in long-term survivors. [Table: see text]

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