Study selection
Through a comprehensive search, we found 213 articles in PubMed and 7 trials in ClinicalTrials.gov. After duplicate, there are 73 articles and 1 trial left. By screening the title and abstract, we excluded 44 articles on the basis of exclusion criteria. Then we view the full texts of remained studies, and finally, 13 articles and 1 trial are involved according to the inclusion and exclusion criteria[13-26]. The overall filter procedures and results are shown in Figure 1.
Study characteristics
The basic information of eligible studies was listed on Table 1. The trials were conducted from 2010 to 2019, including 5 phase Ⅰ trials, 1 phase Ⅰ-Ⅱ trial, 6 phase Ⅱ trials, 1 Ⅲ trial and 1 unknown trial. Among them, patients in 2 phase Ⅰ trials administered mogamulizumab intravenously at a dose of 0.01, 0.1, 0.5, 1.0 mg/kg[17, 21] and 3 phase Ⅰ trials and 2 phase Ⅱ trials received mogamulizumab in combination with other drugs[15, 23-26], while the rest received mogamulizumab at a dose of 1.0mg/kg as a single drug or in comparation of other drugs administered alone[13-16, 18-20, 22]. There were total 1290 patients assessed in these studies, including patients with ATL, PTCL, CTCL, ect.
Overall adverse events analysis
The safety data, grade ≥3 or all-grade AE we extracted, were used to calculate the AEs rate to assess the safety of mogamulizumab. The details of the results were presented in Table 2, 3. In all eligible trials administered mogamulizumab as a single drug, we divided these trials into low dose group (mogamulizumab≤0.1 mg/kg), medium dose group(0.5 mg/kg) and high dose group(1.0 mg/kg) in accordance with the dose. In low dose group, the most common all-grade AE is lymphopenia (0.700, 95% CI: 0.375-0.900) and lymphopenia (0.401, 95% CI: 0.158-0.705) is the only grade ≥3 AE. In medium dose group, the most common all-grade AEs are leukopenia (0.875, 95% CI: 0.463-0.983) and lymphopenia (0.875, 95% CI: 0.463-0.983) while leukopenia (0.767, 95% CI: 0.337-0.955) is the only grade ≥3 AE. In high dose group, the top 5 most common all-grade AEs are lymphopenia (0.805, 95% CI: 0.432-0.957), infusion reaction (0.607, 95% CI: 0.062-0.973), fever (0.472, 95% CI: 0.116-0.859), rash (0.407, 95% CI: 0.210-0.639) and chills (0.401, 95% CI: 0.129-0.751).And lymphopenia (0.648, 95% CI: 0.482-0.787) is the most common grade ≥3 AE. In the trials administered mogamulizumab in combination with other drugs, the top 3 all-grade AEs were neutropenia (0.812, 95% CI: 0.035-0.998), anaemia (0.687, 95% CI: 0.017-0.996), and lymphopenia (0.619, 95% CI: 0.007-0.997). The lymphopenia (0.568, 95% CI: 0.004-0.998) is the most common grade ≥3 AE and other grade ≥ 3 AEs were relatively rare.
Overall efficacy analysis
The overall ORR rate, mean OS and mean PFS were used to measure the efficacy of mogamulizumab in treating cancers. For monotherapy, nine trials[13-16, 18-22] were included in the ORR analysis, and 4 articles[16, 19, 20, 22] were incorporated in the mean PFS analysis. According to our analysis, the overall ORR rate is 0.430 (95% CI: 0.393-0.469) (Fig. 3 A). The median PFS varied from 0.93 to 7.7 months and the pooled mean PFS is 1.060 months (95% CI: 1.043-1.077 Z=125.452, p=0.000) (Fig. 4). Besides, we performed further analyses to evaluate the efficacy between mogamulizumab and other chemotherapeutics. In controlled trials, the HRs for PFS in 2 control trials is 0.53 and 0.71 with a total HR of 0.56 (95% CI: 0.45-0.71, I-squared=0.0%, p=0.348) (Fig. 2), indicating a longer PFS in mogamulizumab group. For mogamulizumab in combination with other therapies, the overall ORR rate is 0.203 (95% CI: 0.022-0.746) (Fig. 3 B). Then we performed subgroup analysis to identify the overall PFS and OS of patients with non-small cell lung cancer in combination therapies. The overall PFS and OS are 2.435 months (95% CI: 1.752-3.119, Z=6.982, p=0.000) and 6.519 months (95% CI: 5.523-7.514, Z=12.836, p=0.000), respectively (Tab. 4).
Assessment of study quality and publication bias
We use Review Manager 5.3 (Copenhagen, Sweden) to measure quality assessment of involved studies. Figure 5 indicates the risk of bias graph and risk of bias summary of all those eligible trials. Overall, the quality of the studies was satisfactory.