Prognostic Features, Treatments, and Disease-Specific Mortality Among Patients with Diffuse Large B-Cell Lymphoma Over the Age of 75: A Single-Center Retrospective Analysis
Authors: Smith Stephen D. , Okada Craig , Chen Andy I. , Spurgeon Stephen E , Fan Guang , Dunlap Jennifer B , Leeborg Nicky , Braziel Rita M. , Maziarz Richard T. 
Published: October 2019

Abstract
Abstract 3673

Background:
Very elderly pts (age > 75) with diffuse large B-cell lymphoma will increasingly be considered for cancer treatment as the population of the United States ages. However, such pts are under-represented in clinical trials, and standardized therapeutic algorithms are lacking. The impact of proliferation index (Ki67) and cell-of-origin are not well-studied in this group. For these reasons, and to inform the development of clinical trials, we retrospectively studied very elderly DLBCL pts since 2002.

Methods:
The Oregon Health and Science University Tumor Registry was queried for all DLBCL cases treated since 2002. Those over 75 years of age were selected for in-depth study under IRB approval. Primary CNS lymphoma, unconfirmed diagnoses, and inadequate follow-up for survival were excluded. Baseline clinical and pathologic features (immunohistochemical, EBV [EBV-encoded RNA, EBER] staining, and translocations involving MYC and BCL2) were recorded. Outcomes including relapse/progression, treatment failure, and death (with cause of death), were analyzed using Kaplan-Meier modeling. Relapse-free survival (RFS) and disease-specific survival (DSS) were measured from diagnosis, censoring deaths not related to lymphoma or immediate therapy complications. Stage, LDH, performance status, disease bulk <10cm, renal failure at diagnosis, initial treatment (RCHOP vs. non-anthracycline), and IPI risk factors were assessed for an impact on outcome using JMP statistical software (SAS) and log-rank testing.

Results:
109 pts over the age of 75 were identified, 76 of whom fit above criteria. Median follow-up is 27 months. Pt characteristics are summarized in Table 1. Extra-nodal involvement was present in 57% of pts; sinus/orbit/ENT disease was seen in 26%. IPI factors were available for a fraction of pts, but an age-adjusted IPI (AA-IPI) of High-Int (2) or High (3) was identified in 15/32.
DSS/OS and RFS curves are shown in Figures 1 and 2. AA-IPI predicted DSS (p=.01). Neither Ki67 index (>80% vs. less) nor BCL6 positivity impacted DSS or RFS. Non-GCB cell-of-origin showed a trend toward poorer RFS (p=.09). > 1 extra-nodal site predicted poor DSS (p=.003) and RFS (p=.005); individually, stage, performance status, LDH, or renal failure at presentation were not prognostic.
RCHOP-like therapy (RCHOP, or REPOCH in 2 pts) was given to 59% (45/76), achieving a 5 year RFS of 60% (censoring non-lymphoma deaths) and OS of 50%. 14 RCHOP pts required a change in regimen due to toxicity, and 4 of these pts died during therapy. Non-anthracycline systemic therapy was administered to 14 (18%) pts, and included RCVP, RCEOP, RCOPP, and single agent R; though not statistically different from RCHOP in DSS or RFS, no evident plateau on the RFS curve was observed with such therapies. Finally, 8% (6) pts were treated palliatively; all died of lymphoma complications at a median of 4 months.
Salvage therapies included R+ chemo (4 pts), prednisone alone (1), rituximab alone (1), radiotherapy (4); median time from relapse to death was 8 months. Overall, 37 deaths have occurred, 27 due to lymphoma or immediate therapy complications.

Conclusion:
Despite 4/45 treatment-related deaths and frequent changes to therapy, RCHOP affords long-term disease control in a proportion of very elderly pts. This suggests a regimen alternating RCHOP with other active agents can be tolerated and may produce the ideal balance of efficacy and safety in this pt population. High AA-IPI pts should be targeted for novel approaches, as pathologic biomarkers (Ki67, cell-of-origin by IHC) do not predict relapse or disease-specific survival outcomes. Further trials in this under-studied population are warranted.

Disclosures:
Spurgeon: Gilead: Research Funding.