Patient baseline characteristics such as age, International Prognostic Index (IPI), and tumor stage may significantly impact the variability in efficacy observed in clinical trials assessing systemic therapy for diffuse large B-cell lymphoma (DLBCL), according to a study recently published in the Journal of Comparative Effectiveness Research. 

Currently, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immuno-chemotherapy constitutes the standard of care for patients with DLBCL. Nonetheless, a significant percentage of these patients are resistant or relapse after R-CHOP. 

Although several novel therapies for patients with resistant or relapsed DLBCL have emerged over the last decade, the comparative efficacy of these alternatives has not been established. Several authors suggest that the great variability of baseline characteristics among patients included in clinical trials could contribute to this issue. 

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Therefore, the authors aimed to summarize the findings of clinical trials regarding therapeutic alternatives for patients with resistant or relapsed DLBCL who are ineligible for or have failed stem cell transplants through a systematic review of multiple databases.

After applying exclusion criteria, 17 trials assessing the efficacy of 11 systemic therapy regimens were included in the review. The sample sizes of each trial varied from 13 to 269 patients. 

The authors observed that the factors most strongly associated with a negative overall response rate varied greatly among the populations included in each trial. 

These factors included multiple lines of therapy, higher Eastern Cooperative Oncology Group performance status, high or intermediate IPI, and primary refractory disease.

Researchers noted that changes in clinical management over the 16 years covered in the review could also impact the variability in efficacy observed. Furthermore, outcome assessment was heterogeneous among trials, which could also have had an impact on variability.

“The variations are particularly important considerations in clinical and healthcare decisions based on the comparisons of systemic therapies in resistant or relapse DLBCL patients ineligible for or experienced with transplant, where many of the trials are either single-arm or RCTs without a common comparator,” the authors wrote.

“Therefore, indirectly comparing efficacy results from these varied trials ought to use appropriate statistical techniques that take into account the differences in patient baseline characteristics across the trials.”

Reference

Miller SD, Lozano-Ortega G, Mutebi A, et al. Systematic review of outcomes and patient heterogeneity in relapsed or refractory diffuse large B-cell lymphoma. J Comp Eff Res. Published online November 23, 2022. doi:10.2217/cer-2022-0146