Hodgkin Lymphoma in Older Patients- a Retrospective Analysis of the Polish Lyphoma Reasearch Group
Authors: Wrobel Tomasz , Dobrzynska Olga , Chmielowska Ewa , Nowara Elzbieta , Badora-Rybicka Agnieszka , Szulgo Anna , Sorbotten Natalia , Jurczak Wojciech , Agnieszka Giza , Adamowicz Krzysztof , Bartoszko Agata , Lesniewski-Kmak Krzysztof , Knopinska-Posluszny Wanda , Kulikowski Waldemar , Kroll Renata , Balcerzak Andrzej , Spychalowicz Wojciech , Kalinka-Warzocha Ewa , Kumiega Beata , Drozd-Sokolowska Joanna E , Subocz Edyta , Salek Agata , Holojda Jadwiga , Pogrzeba Joanna , Dybko Jaroslaw , Poreba Rafal , Zaucha Jan Maciej 
Published: October 2019

Abstract
Elderly patients with Hodgkin lymphoma (HL) have poor prognosis. The inferior outcome has been attributed to a variety of factors including histologic differences, higher incidence of advanced stages, presence of comorbidities, poor performance status, inability to tolerate chemotherapy at full dose and increased treatment-related toxicity and mortality. ABVD is recommended and widely used for elderly patients (pts) although no prospective studies exist to justify this guideline. Moreover there are only few studies, yet most limited in numbers of pts, evaluating the results of HL treatment in elderly population.
Here we present the retrospective analysis of outcome of 414 elderly HL pts treated by PLRG allied centers between 2003-2013. Group consisted of 237 men and 177 women. Their median age was 60,5 (50-93) years with the following age ranges:50-59 years-50%, 60-69 years-27%, ≥ 70 years-23%. Histology subtype showed predominance of nodular sclerosis 56%, followed by mixed cellularity 30%. 168 (41%) pts presented with early stage (I,II Ann Arbor) and 246 (59%) with advanced stage (III, IV Ann Arbor). 384 patients were treated with ABVD or ABVD-like regimen, few with CHOP-like(14), BEACOPP(9), PVAG (5) or with corticosteroids only(2). The median follow-up was 28,7 months. The response rates according to age groups are shown in Table 1. Progression free survival (PFS) and overall survival (OS) for all pts were 21 months and 39,5 months, respectively. Median PFS in group 50-59yrs and group 60-69yrs was similar 21,3 months and 22months respectively but was statistically significantly longer than in pts≥70 years old (16 months) (p<0,05). Median OS in group 50-59, 60-69 and ≥ 70 years old was 50,5 months, 35,2 months, 21,5 months, respectively (p<0.05) .
Comorbidities were evidently more common in older patients: 30% in 50-59 yrs old, 65% in 60-69 yrs old, 85% in ≥70 yrs old. However, irrespective of age, patients with high burden of cardiovascular disease showed significantly poorer OS and PFS than those with comorbidities other than cardiovascular (OS 29 months vs 41 months, PFS 9 months vs 21 months, respectively, p <0.05).
Univariate analysis with Cox regression model including age ≥60, clinical stage >II, presence of B symptoms, IPS>2, serum albumin level below normal, ECOG>1, male sex, erythrocyte sedimentation rate ESR>10 and white blood cells count above the upper limit showed that age ≥60 (p=0.02), clinical stage >II (p=0.04), B symptoms (p=0.01), IPS>2 (p=0.02) and low serum albumin level (p=0.001) had statistically significant negative impact on OS. Multivariate analysis confirmed the significantly negative impact on OS of age ≥60 (p=0.005), IPS>2 (p=0.004) and low albumin level (p=0.002).
Although, in our cohort overall response rate was better than in other studies, the outcome is still worse than in younger patients with HL. Specifically the prognosis of patients older than 60 years is even worse than patients who are 10 years younger. Our data also show that ABVD is not appropriate for very elderly patients (≥ 70 years old) and also for those with cardiovascular comorbidities irrespective of age. To find successful strategy for older and frail patients novel approaches should be tested in future trials.
Table 1. Response rate according to age. Age, range 50-59 years old 60-69 years old ≥ 70 years old Ann Arbor stage n I-II 89 III-IV 123 I-II 43 III-IV 69 I-II 36 III-IV 54 CR* 79,8% 61,8% 69,8% 60,9% 52,8% 55,6% PR 18,0% 19,5% 23,3% 21,7% 38,9% 27,8% PD 0,0% 4,9% 0,0% 7,2% 0,0% 9,3% 3NR 2,2% 13,8% 7,0% 10,1% 8,3% 7,4%
*CR- complete remission, PR- partial remission, PD- progressive disease, NR- no response.

Disclosures
No relevant conflicts of interest to declare.