To the editor,

Follicular lymphoma (FL), a common indolent B-cell lymphoma, is characterized by its high heterogeneity in clinical characteristics and outcomes [1]. Demographics, clinical characteristics, treatment patterns and outcomes of FL patients have been well documented in Western countries [2, 3]. However, this information is largely lacking in China. To understand clinical presentations, treatments and prognosis of Chinese FL patients, we performed a retrospective multicenter study, which enrolled 1845 patients (age > 18 years) with newly diagnosed FL between 2000 and 2020 in China. Patients and methods for this study are described in detail in Additional file 1.

Demographics and clinical characteristics of the patients enrolled in this study are summarized in Table 1. The median age at diagnosis was 53 years in our cohort, similar to that reported earlier for Chinese FL patients (49–51 years) but much younger than that reported in Western cohorts (60–65 years) [2,3,4,5]. Consistent with the prior study from China [4], Chinese FL patients had relatively lower rate of ECOG ≤ 1 than non-Chinese counterparts, reflecting poor performance status; moreover, approximately 40% of Chinese FL patients had extranodal involvement sites of > 1, significantly higher than that demonstrated in the cohorts of Western countries (5–25%) [2, 3]. Although the incidence of bone-marrow infiltration (BMI) in this cohort (28%) was higher than that reported previously for Chinese FL patients (15.2%) [4], the BMI rates in Chinese FL patients were lower than that in Western patients (29–52%) [2,3,4]. Other clinical features of FL patients in our cohort were comparable to those reported for Chinese FL patients and in the Western cohorts [2,3,4,5].

Table 1 Baseline patient and disease characteristics in the entire cohort (n = 1845)
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Treatment patterns and therapeutic responses are detailed in Additional file 2. In our cohort, 91% of FL patients received systemic chemotherapies, among which CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) ± rituximab (R) was the most frequently used regimen, probably representing the major regimen for frontline treatment of FL in China, in accordance with the earlier report [4]. However, only 1% of patients received bendamustine plus rituximab, due to unavailability of bendamustine in China until 2019 [6]. Unlike approximately 20% of FL patients treated with observation in the cohorts of Western countries [7], only 7% of Chinese FL patients were administered with watchful waiting. In the study, overall response rate (ORR) was 72% with 46% complete remission (CR). 5-year progressive-free (PFS) and overall survival (OS) for all patients were 61% and 89%, respectively (Fig. 1A, B). Both were analogous to those observed previously in Chinese FL patients and several Western cohorts [4, 8, 9]. We found that rituximab-based induction therapy (Ri) followed by rituximab maintenance (Rm) resulted in the best outcomes (both PFS and OS), consistent with the findings from another real-world study in Chinese population [10]. Ri only was superior to Rm only (Fig. 1C, D). This observation suggests that incorporating rituximab into induction treatment might be more beneficial than using rituximab for maintenance if patients could not afford long-term usage of this costly agent.

Fig. 1
figure 1

Clinical prognostic analysis of Chinese FL patients in the entire cohort and different subgroups. A, B 5-year progression-free survival (PFS, A) and overall survival (OS, B) of Chinese FL population in the whole cohort. C, D Kaplan–Meier curves of PFS (C) and OS (D) according to different rituximab administrations (no rituximab treatments (No R), first-line induction chemotherapies with rituximab (Ri), maintenance with rituximab (Rm), and Ri plus Rm regimens). E OS for patients with or without histological transformation (HT). F OS for patients with HT prior to or post-treatment

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Histological transformation (HT) represents a crucial feature of FL and correlates with unfavorable outcomes [11]. Transformed FL (t-FL) can happen prior to or post-chemotherapy [12]. In our cohort, 125 patients (7%) experienced HT, of which 3% and 4% of transformed cases were observed prior to or post-treatment, respectively. Analogous to those described in previous studies involving Western countries, patients with t-FL displayed poorer outcomes than those with non-transformed FL (nt-FL; Fig. 1E; P = 0.0002). In this study, patients with t-FL prior to treatment had 87% of 5-year OS, which was similar to those with nt-FL but significantly better than those whose disease was transformed post-chemotherapy (Fig. 1F; P = 0.040). This observation suggests that patients with t-FL prior to therapy could be treated as those with nt-FL, but intensive chemotherapies should be administrated for patients with t-FL post-therapy.

This study reveals that Chinese FL patients were much younger and had higher extranodal involvement but lower BM infiltration than Western FL patients. Most Chinese FL patients received systemic chemotherapies, with CHOP ± R representing the most common regimen. In terms of ORR, CR, PFS and OS of FL patients, no significant difference was observed between our cohort and the cohorts previously reported in China and Western countries. Ri plus Rm yielded the most favorable outcome, while Ri only was superior to Rm only when they were applied separately. 7% of FL patients underwent HT, of which 3% and 4% of cases transformed prior to or post-chemotherapy. The latter had poorer outcome than the former. Collectively, this large retrospective study outlines the clinical features and outcomes of Chinese FL patients, which might lay a foundation for future clinical investigation of FL in China.