Polatuzumab-R-CHP vs R-CHOP in older DLBCL: Survival benefit, infectious toxicity, and cost implications in middle-income health systems.

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Background: Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) improves progression-free survival (PFS) compared with R-CHOP in diffuse large B-cell lymphoma (DLBCL). However, in older patients and in middle-income health systems, its real-world value remains uncertain because of infectious toxicity and high drug acquisition costs. We therefore aimed to synthesize comparative evidence on survival outcomes, infectious toxicity, and economic impact of Pola-R-CHP versus R-CHOP in this context. Methods: We conducted a systematic review of randomized and real-world comparative studies evaluating Pola-R-CHP versus R-CHOP in DLBCL. Random-effects meta-analyses were performed for PFS and overall survival (OS) hazard ratios (HRs) and febrile neutropenia (FN) risk ratios (RRs). Cost-effectiveness evidence was reviewed narratively from published economic models. Drug acquisition costs were estimated for Indonesia using publicly available patient access programs. Results: Across included studies, Pola-R-CHP improved PFS compared with R-CHOP (pooled HR 0.61, 95% CI 0.47 - 0.79), while OS data were immature and did not show a consistent survival advantage. FN risk estimates were heterogeneous; the primary pooled analysis did not demonstrate a statistically significant difference (RR 1.22, 95% CI 0.66–2.28). Sensitivity analysis excluding a single-center outlier suggested a possible increase in FN among older patients treated with Pola-R-CHP (RR 1.52, 95% CI 0.94–2.45). A published Italian cost-utility analysis reported modest gains of approximately 0.5 quality-adjusted life-years (QALY) with Pola-R-CHP at high income-country prices, and other health technology assessments reached similar conclusions under trial-based assumptions. In Indonesia, the estimated polatuzumab acquisition cost was approximately IDR 424 million per patient for six cycles, despite a patient access program. Conclusions: Although Pola-R-CHP provides a consistent PFS benefit, potential increase in febrile neutropenia in older patients and substantial upfront costs raise important concerns regarding its real-world value in middle-income health systems. Careful patient selection and context-specific economic evaluation are warranted. Keywords: Diffuse large B-cell lymphoma; Polatuzumab vedotin; Cost and value assessment.