A Prospective, Observational Study on the Safety and Effectiveness of Rituximab Plus Chemotherapy As the First-Line Treatment of Diffuse Large B-Cell Lymphoma
Authors: Feng Jifeng , Wu Jianqiu , Song Yongping , Su Liping , Zhang Mingzhi , Li Wei , Hu Yu , Zhang Xiaohong , Gao Yuhuan , Feng Ru , Wang Wei , Niu Zuoxing , Peng Jiewen , Li Xiaolin , Ouyang Xuenong , Wu Changing , Zhang Weijing , Zeng Yun , Xiao Zhen , Liang Yingmin , Zhuang Yongzhi , Wang Jishi , Sun Zimin , Bai Hai , Cui Tongjian 
Published: October 2019

Abstract
Background: The efficacy and safety of rituximab(R)-based immunochemotherapy, the standard regimens for patients (pts) with diffuse large B-cell lymphoma (DLBCL) which is more common in Asia than in Western countries, are well confirmed in RCT studies. However, the safety and effectiveness of R+chemo for DLBCL in real world use is not widely reported, especially population are normally excluded in RCT studies. The objective of this observational study is to investigate the safety and effectiveness of R+chemo as 1st line treatment for Chinese DLBCL in routine clinical practice.
Methods: This study was a multicenter, prospective, single-arm observational study conducted in China. DLBCL pts eligible to receive R+chemo (CHOP or non-CHOP) as 1st line treatment were enrolled with no specific exclusion criteria. The primary endpoint was safety. Data on safety and effectiveness were collected from medical records 120 d after the last R dose was administered. This study was registered in clincialtrials.gov (NCT01340443).
Results: In total, 279 pts (162male/117femal) with a median age of 57 yrs (range 13 to 88 yrs) were included in the safety analysis set. By IPI criteria, 50.2% of pts were low risk, 25.4% low-intermediate risk, 16.5% intermediate-high risk, 7.2% high risk and 0.7% with unknown risk. The most common concomitant diseases observed are liver (44,15.8%), heart (23, 8.2%), kidney (9, 3.2%) or lung (7, 2.5%) disease. Pts received R+chemo treatment with a median cycle of 6 and a median interval of 24 d. In total, 52.7% pts had grade 3-4 AEs and 16.8% pts had SAE (Table 1). AE related death was 1.1% (n=3). 67.0% pts had any grade hematologic toxicity and the most common grade 3/4 hematologic toxicities were leukocytopenia (29.7%), erythrocytopenia (3.9%), and thrombocytopenia (5.7%). Infection (46.2%), gastrointestinal toxicity (45.2%), and liver toxicity (12.5%) were common non-hematologic toxicities. The AEs of special population (with common concomitant and very young/older DLBCL) are listed in Table 2. For HBV management, the incidence of HBV reactivation in HBsAg+, HBsAg-/HBcAb+, HBsAg-/HBcAb-, and undefined pts was 12.5% (3/24), 4.3% (3/69), 0.7% (1/149), and 2.7% (1/37), respectively, no death due to HBV reactivation 120 d after the last R dose was administered. The detail outcomes of HBV reactivation management in this study was reported in EHA 2014. For ITT population (n=258), the overall response rate was 93.7%. Rates of complete response (CR), unconfirmed CR (CRu) and partial response (PR) were 55.0%, 18.2% and 20.9%, respectively.
Summary and Conclusions: During this observation study, the incidence of adverse events of R+chemo as 1st line for DLBCL in real world were tolerable and consistent to previous reports. The AEs in special DLBCL sup-population (very younger, older or with common concomitant disease) are well tolerated too. R+chemo treatment brought more than 90% response rate in these Chinese pts might due to the pts with relative low IPI score. More education on standard management of HBV is needed. Accordingly, this real world study further validates the safety and effectiveness of using R+chemo to treat pts with DLBCL.
Table 1: The Hamatologist and common non-hematologist AEs ¡¡ Any grade, n (%) Grade 3/4, n (%) SAE, n (%) Death, n (%) Any toxicity 267 (95.7) 147 (52.7) 47 (16.8) 3 (1.1) Hematological toxicity 187 (67.0) 104 (37.3) 6 (2.2) 0 (0.0) Bone Marrow Failure 23 (12.3) 14 (7.5) 2 (1.1) 0 (0.0) Leukocytopenia 167 (59.9) 83 (29.7) 4 (1.4) 0 (0.0) Erythrocytopenia 62 (22.2) 11 (3.9) 0 (0.0) 0 (0.0) Thrombocytopenia 24 (8.6) 16 (5.7) 1 (0.4) 0 (0.0) Common Non-hematological toxicity Infection 129 (46.2) 48 (17.2) 34 (12.2) 2 (0.7) Gastrointestinal toxicity 126 (45.2) 7 (2.5) 2 (0.7) 0 (0.0) Liver toxicity(SMQ) 663(22.6) 10 (3.6) 2 () 0 (0.07) Cardiac toxicity(SMQ) 29 (10.4) 4 (1.4) 3 (1.1) 1 (0.4) Kidney toxicity 9 (3.2) 1 (0.4) 0 (0.0) 0 (0.0)
Table 2: The AEs of special population (with common concomitant and very young/older DLBCL) ¡¡ Total common concomitant disease ¡¡ Age ¡¡ Cardiac History Liver History ¡¡ <=18 or >=80 19-79 ¡¡ (N=279) (N=23) (N=44) ¡¡ (N=10) (N=269) ¡¡ No.% No.% No.% ¡¡ No.% No.% AE 267 (95.7) 22 (95.7) 42 (95.5) ¡¡ 10 (100) 257 (95.5) SAE 47 (16.8) 7 (30.4) 11 (25.0) ¡¡ 3 (30.0) 44 (16.4) AESI 46 (16.5) 6 (26.1) 9 (20.5) ¡¡ 2 (20.0) 44 (16.4) ADR 226 (81.0) 21 (91.3) 36 (81.8) ¡¡ 10 (100) 216 (80.3)

Disclosures
No relevant conflicts of interest to declare.