Treating Indolent Lymphoma in Older Adults: What Is the Right Way?
Authors: Horesh Nurit , Lavi Noa , Dann Eldad , Horowitz Netanel A. 
Published: November 2019

Abstract
Introduction: The treatment of hematological malignancies in older adults is an emerging and important issue due to the aging population trend as well as drug-related toxicities in pts (pts) with comorbidities. Indolent lymphomas constitute a subgroup of incurable non-Hodgkin lymphomas characterized by multiple relapses. Anthracycline containing chemo-immunotherapy regimens (ACR) such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) are very active in indolent lymphomas, resulting in a long progression-free survival (PFS). Due to their high rate of associated toxicities, such regimens are less likely to be given to the elderly population. Currently, there is no consensus regarding the treatment of indolent lymphomas in older adults. The present study assessed overall survival (OS), time to next treatment (TNT) and treatment-associated toxicity in this distinctive subpopulation of pts with indolent lymphoma, aiming to develop an optimal approach to the management of such pts.
Methods: This retrospective cohort analysis included pts with indolent lymphoma (histology diagnosis of follicular lymphoma, marginal zone lymphoma, Waldenstrom's macroglobulinaemia and indolent lymphoma not otherwise specified) aged ≥60 at therapy initiation (1st line) treated with either an ACR or a non-ACR at the Rambam Department of Hematology and Bone Marrow Transplantation between the years 2000 and 2012. All regimens included rituximab. OS, TNT and treatment-related toxicity (neutropenic fever and hospital admission due to noninfectious causes during the treatment period) were assessed.
Results: Forty three pts treated with an ACR and 55 pts receiving a non-ACR were included in the analysis. Clinical characteristics, response to therapy and treatment modification data are presented in table 1. The median age was 67 years in the ACR group and 73 years in the non-ACR group; median duration of the follow-up was 4.3 years (range 0.1-11.9 years). No difference in terms of high risk co-morbidity score, defined as modified Charlson co-morbidity score ≥5 (Charlson et al, 1987), was found between the ACR group and the non-ACR group. Significantly more pts with follicular lymphoma were treated with ACR compared to non-follicular indolent lymphomas. There was no difference in CR rate between the ACR and non-ACR groups. In a univariate analysis, OS was found to be significantly higher in the ACR group, but in the multivariate analysis, OS appeared to be influenced only by age. The cause of death was disease-related in 8 pts (100% of deaths) in the ACR group and in 7 pts (64%) in the non-ACR group (data on the cause of death were available for 11 out of 18 pts from the non-ACR group). The median TNT was longer in the ACR cohort, but the difference did not reach statistical significance. No difference was found between the ACR and non-ACR groups in terms of major treatment-related toxicities assessed by the number of hospital admissions because of infection or other causes. Dose adjustments and treatment delays were far more frequent in the ACR cohort. This study is limited by its retrospective nature, the small number of patients and a significantly higher number of pts with follicular lymphoma treated in the ACR group.
Conclusions: The present analysis of a cohort of older adults with indolent lymphoma treated with chemo-immunotherapy regimens in routine clinical practice has demonstrated that ACR was safe and efficacious. When approaching older adults suffering from indolent lymphoma, the considerations of quality of life (time without the need of further treatment, the minimal number of hospital admissions and minimal number of infections requiring hospitalization) should play a major role in treatment decision-making. In the current study, ACR was not inferior to non-ACR in terms of toxicity. A trend to an improved OS and longer TNT was demonstrated in the ACR group. The patient age should not deter physicians from using ACR in older adults.
Table 1. Parameters ACR N=43 Non-ACR N=55 P value Age, median 67 73 0.05 Pts with modified Charlson comorbidity score ≥5 (%) 7 (17) 10 (19) 0.55 Pts with follicular lymphoma (%) 33 (77) 27 (49) 0.007 CR rate (%) 30 (70) 33 (60) 0.4 4-year OS, % 81 67 <0.04 Median time to next treatment, months 90 55 0.2 Dose adjustments 65 37 0.008 Treatment delays 57 37 0.06

Disclosures
No relevant conflicts of interest to declare.