Patterns of Care of Diffuse Large B Cell Lymphoma Patients 80 Years and Older: Worse Outcomes after Treatment without Increased Relapse
Authors: Keenan Madison , Boughan Kirsten Marie , Cooper Brenda , Gallogly Molly M , Gerson Stanton L. , Lazarus Hillard M , Malek Ehsan , Metheny Leland , Otegbeye Folashade , Tomlinson Benjamin K. , Moore Erika , Oduro Kwadwo Asare , Beck Rose , Meyerson Howard , de Lima Marcos , Caimi Paolo F 
Published: October 2019

Abstract
Introduction: Very advanced age (≥80 years) DLBCL patients have worse prognosis. These unfavorable outcomes are largely considered to be a result of the combined effects of increased comorbidities, frailty, diminished tolerance and access to effective chemoimmunotherapy. It is not clear yet whether DLBCL patients of very advanced age have disease that is intrinsically more aggressive.
Methods: We accessed the Stem Cell Transplant and Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2000 and 2016. Information collected included demographic characteristics, baseline laboratory and disease information, as well as treatment details. Progression free survival and overall survival were calculated from time of diagnosis using Kaplan Meier methodology, comparisons were done with log rank. Cumulative incidence of relapse with death as competing risk was calculated for patients who underwent treatment, comparisons between age groups were done with the Gray test.
Results: A total of 542 DLBCL patients were identified, 85 (16%) were older than 80 years. Table 1 shows the baseline demographic and disease characteristics. Older patients had a higher incidence of comorbidities, specifically cardiovascular comorbidities, prior renal insufficiency, and hyperlipidemia. Expectedly, very elderly patients had higher R-IPI, with a trend towards worse performance status that did not reach statistical difference. The proportion of patients diagnosed with non - germinal center DLBCL was not different than younger DLBCL patients, and there was no statistical difference in the incidence of double expressor or double hit lymphomas, possibly secondary to the small number of patients tested.
A smaller proportion of patients ≥ 80 years received antineoplastic therapy (89% vs. 98%, p = 0.001), and use of less intense therapy was more common (table 2). Sixty one percent of patients, however, were still treated with R-CHOP (38.8%) or R-miniCHOP (22.2%). The overall response rate (ORR) for any therapy was 68.2%, lower than the ORR for younger patients (85.9%, p = 0.007). When only patients treated with RCHOP/R-miniCHOP were included, the difference in ORR was smaller, though still statistically significant (77.5% vs. 89.8%, p = 0.021). Median number of cycles was similar (5 vs. 6 cycles, respectively). Patients of all ages treated with single agent rituximab presented an ORR of 43%.
After a median of 40 months follow up, estimated 4-year overall survival was 42% (95% CI 31-54%) for patients ≥ 80 years, 67% for patients aged between 60 and 79 years (95% CI 61-74%) and 78% for patients < 60 years (95% CI 73-84%) (Figure 1). Four - year survival for patients ≥80 years treated with R-CHOP or R-miniCHOP chemoimmunotherapy was 50% (95% CI 36-65%) vs. 75% for younger patients (95% CI 70-79%) (p<0.001), with 4-year PFS of 48% vs. 63% (95% CI 58-68%) (p = 0.04). Cumulative incidence of relapse (with death in remission as competing risk) for chemoimmunotherapy - treated patients at 1 and 4 years was 10% (95% CI 4-22%) and 20% (95% CI 11-37%), respectively for patients older than 80 years and 20% (95% CI 11-36%) and 29% (95% CI 25-35%), respectively for younger patients (p = 0.12) (Figure 2). There was no observed difference in the rates of disease - related mortality (53% vs. 61%, p = 0.5).
Conclusions: Very elderly (≥80 years of age) DLBCL patients have significantly worse overall survival, progression free survival, and treatment response rates than younger patients. However, when chemoimmunotherapy is feasible, disease relapse rates are comparable to those of younger patients, and increased mortality does not appear to be a result of increased disease relapse. Additional research is needed to establish more widely applicable, better tolerated effective treatment regimens for this patient population.

Disclosures
Lazarus: Pluristem Ltd.: Consultancy. Malek:Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Tomlinson:Foundation Medicine: Consultancy. Caimi:Genentech: Other: Advisory Board PArticipation, Research Funding; Kite Pharma: Other: Advisory Board Participation; Celgene: Speakers Bureau; Kite Pharma: Other: Advisory Board Participation.