Comparison of Non-Chemotherapy Options for Older Adults (65-75 years) with Early Relapse/Refractory DLBCL Not Receiving CART: A Real-World Analysis
Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) in patients aged ≥65 who are ineligible for or declining chimeric antigen receptor T-cell therapy (CART) represents a major therapeutic challenge. While CART therapy offers curative potential, its usage in older adults is frequently limited by comorbidities, performance status, logistical barriers, or rapid disease kinetics. For this population, non-chemotherapy options have emerged as an acceptable approach including the combination of Tafasitamab and Lenalidomide (Tafa/Len), Epcoritamab (Epco) or Glofitamab (Glofi). The aim of this study is to do a first real-world comparison of survival outcomes among these treatment options for older adults with early R/R DLBCL.
Materials and Methods/Case Presentation/Objective: We conducted a retrospective study using data from the TriNetX Global Collaborative Network. Eligible patients were of 65-75 years old with a documented diagnosis of DLBCL which had initially received R-CHOP or Pola-R-CHP and who required subsequent line of treatment within the next 12 months with either Tafa/Len, Epco or Glofi. Patients who received CART therapy were excluded. No crossover among treatments was allowed. 3 analyses were carried out: (1) Tafa/Len vs Glofi (2) Tafa/Len vs Epco (3) Epco vs Glofi. Cohorts were balanced using propensity score matching for age at diagnosis, male, lactate dehydrogenase level, comorbidities and concomitant medications. Kaplan-Meier survival curves were used to assess overall survival (OS) over a 5-year follow up period.
Results/Description/Main Outcome Measure(s):
221 patients were identified from 39 healthcare organizations; of these 56 received Tafa/Len, 93 Epco and 72 Glofi.
(1) Tafa/Len vs Glofi
After balancing each cohort had 38 patients for analysis. The survival probability at 5 years of these patients were 25% for Tafa/Len vs 59% for those receiving Glofi. A statistically significant difference was noted in OS favoring Glofi treatment [p-value of 0.0362] (HR 2.108, 95% CI 1.032,4.307).
(2)Tafa/Len vs Epco
After balancing, each cohort had 35 patients for analysis. The survival probability at 5 years of these patients were 27% for those with Tafa/Len vs 28% for those with Epco. No difference in OS was noted among groups [p-value of 0.4157] (HR 0.777, 95% CI 0.423,1.429).
(3) Epco vs Glofi
After balancing, each cohort had 54 patients for analysis. The survival probability at 5 years of these patients were 28% for those with Epco vs 56% for those with Glofi. A statistically significant difference was noted in OS favoring Glofi treatment [p-value of 0.0329] (HR 1.923, 95% CI 1.043,3.544).
Conclusion(s).: Based on these results, Glofi may be the preferred regimen for older adults with early R/R DLBCL not undergoing CART. The survival benefit was significant against both Epco and Tafa/Len. However, further prospective studies should be carried out to validate this finding as it the results will be crucial for this frail population. Ultimately choosing among these regimens in patients ≥65 years requires balancing the line of therapy, tumor biology, fixed-duration treatment vs continuous suppression, route of administration, toxicity profiles and patient preference to balance the survival benefit while preserving quality of life.
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