Standard Dose Rituximab Research Articles

Comparing the Impact of Rituximab Dosing on Longitudinal ADAMTS13 Parameters in TTP

Introduction The use of rituximab to prevent clinical TTP relapse is widely accepted practice. However, the optimal dosing and regimen remains unclear with a variety used across treating centres. ‘Standard’ dosing is extrapolated from dosing for lymphoproliferative diseases: an equally efficacious lower dose would be time & cost-saving. We are investigating the impact of low dose (4 x 200mg weekly) vs standard dose rituximab (4 x 375mg/m 2 weekly) on ADAMTS13 response utilising prospectively collected samples from 69 ADAMTS13 relapse episodes from 4 UK sites who received elective treatment between 2017-2022 (REC: 17/LO/1055). A subset analysis of the cohort was performed, investigating open/closed ADAMTS13 conformation from time of elective rituximab treatment to subsequent rituximab retreatment. Method ADAMTS13 activity was measured at fixed timepoints from first day of elective rituximab on days 1, 8, 15 & 22, month 1, 3, 6 and then 6 monthly until retreatment. Open/closed ADAMTS13 conformation was analysed in a subset of 31 episodes with the 1C4 ELISA and ADAMTS13 antigen ELISA at 4 different timepoints (ADAMTS13 activity <15IU/dL or %; peak ADAMTS13 activity; interim follow-up sample after peak ADAMTS13 and at next ADAMTS13 relapse). Results Median time from one elective rituximab treatment to the next was 16 months (range: 2 - 64, IQR: 9 - 24) for the subset. Time to ADAMTS13 activity normalization was compared in 26 episodes: 5 episodes were excluded as they failed to achieve ADAMTS13 normalization. 17/31 had low dose and 14/31 standard dose. There was no significant difference in the rate of ADAMTS13 normalization in the low dose compared to standard dose rituximab regime, with median 34 days ( IQR: 18 - 99, range: 14 - 266) and 21 days (IQR: 15 - 65, range: 14 - 94) respectively. 13 patients remained in an open ADAMTS13 conformation at all four timepoints, of which 9 had received low dose rituximab. 5 of 13 patients did not achieve a normal ADAMTS13 activity (i.e. >60IU/dL) at any timepoint, with 3 having received low dose & 2 standard dose rituximab. These 13 patients had a slightly shorter time period between elective rituximab treatment episodes with a median of 8 months (range: 2 - 25, IQR: 6 - 15). In 3 patients, ADAMTS13 remained closed on the follow up sample 3 months after peak ADAMTS13 activity (mean 100IU/dL), despite subsequently relapsing 2, 8 & 12 months later. Two had received standard dose rituximab. 14 patients had a closed conformation at peak ADAMTS13 activity, but a subsequent open conformation on follow up sample testing, despite a normal ADAMTS13 activity (median: 82IU/dL, IQR: 72-86). The 7 patients receiving standard dose rituximab converted to an open conformation in 6 months (IQR: 3 - 12) compared to the 7 low dose patients who switched at 4 months (IQR: 3 - 12). Subsequent ADAMTS13 relapse after detection of an open conformation occurred at a median of 6 months later (range: 4 - 8) in the standard dose group and 8 months (range: 4 - 19) in the low dose group. Lastly, 1 patient had no follow up sample after peak ADAMTS13 activity (& closed confirmation), presented with ADAMTS13 relapse (<15IU/dL) and open conformation 7 months later. Of the 31 episodes, ADAMTS13 activity & antigen results were not significantly different between the two rituximab groups for both peak ADAMTS13 activity and follow up timepoints. At peak ADAMTS13 activity, approximately 31% of patients had an open conformation in the standard dose group compared to 69% in the low dose group. In the follow up samples, this increased to 85% open conformation in the standard dose group and 93% open in the low dose group. For two of the patients, with more than one episode of elective rituximab treatment during the study, a closed ADAMTS13 conformation was again achieved after subsequent rituximab treatment. Conclusion We studied the impact of low dose and standard dose rituximab on longitudinal parameters in ADAMTS13 relapse in TTP. Overall, there were no significant differences between open vs. closed conformation at peak ADAMTS13 activity and an interim follow up timepoint between low dose and standard dose rituximab. A higher proportion of patients on low dose rituximab failed to achieve closed conformation at any timepoint but numbers are small. Importantly, our data suggests that regardless of rituximab dose, the open conformation is not indicative of imminent ADAMTS13 relapse as patients required retreatment after a further 7 months on average.

Comparison of Time to Relapse between Low-Fixed Dose Versus Standard-Dose Rituximab in the Treatment of ITP, TTP, and AIHA

Background: The optimal Rituximab dosing regimen for the treatment of immune thrombocytopenia purpura (ITP), autoimmune hemolytic anemia (AIHA), or thrombotic thrombocytopenia purpura (TTP) has not been well established. To our knowledge, there has not been a randomized trial examining the time to relapse with the different Rituximab dosing regimens (low-fixed dose of 100 mg x 4 weekly doses versus standard dose of 375 mg/m2 x 4 weekly doses) in the treatment of ITP, TTP, and AIHA. Previous comparative studies have shown that the weekly low-fixed Rituximab dosing regimen has been shown to be just as effective in treating these diseases as demonstrated by similar response and duration of response. Therefore, we conducted a comparative analysis to evaluate the time to first recurrence after being treated with Rituximab. Methods: We collected clinical data from a single center of patients with diagnosis of ITP, TTP, or AIHA and were treated with 4 weekly low-fixed or standard dose Rituximab. Time to first recurrence was measured to compare if there was a significant difference between the two Rituximab dosing regimens. Kaplan-Meier time to recurrence estimates were used to generate time to recurrence curves. Results: Of the 30 patients analyzed, 10 patients were diagnosed with AIHA, 12 patients with ITP, and 8 with TTP. All patients had a complete response (CR) per the specific disease CR definition prior to first disease recurrence. 17 patients were treated with standard dose Rituximab and 13 patients were treated with low-fixed dose Rituximab. 17 patients did not have a recurrence in the selected time frame of the study. Recurrence was observed in 40% of the AIHA patients, 50% of the TTP patients, and 37.5% of TTP (P=0.8297). 47% females had a recurrence compared to 36% males (P=0.7084). Recurrence was observed in 61% patients who received the low-fixed dose Rituximab and 29% of patients who received the standard dose Rituximab (P=0.1376). The median time of recurrence was 16 and 27 months among patients who received low-fixed dose vs standard dose Rituximab, respectively (P=0.1914). Conclusions: The use of low-fixed dose Rituximab versus standard dose Rituximab for treatment of ITP, TTP, and AIHA appears to have a higher recurrence rate but did not meet statistical significance. The median time difference in recurrence was 9 months. This could potentially be significant in a larger study population. Further investigation through large, randomized controlled trials is needed to assess if there is a significant difference in recurrence rate and time to recurrence between the two Rituximab dosing regimens.

Low Versus Standard Dose of Rituximab in Adult Patients with Relapsed or Refractory Primary Membranous Nephropathy: Does It Make Any Difference?

Low Versus Standard Dose of Rituximab in Adult Patients with Relapsed or Refractory Primary Membranous Nephropathy: Does It Make Any Difference?

Low dose versus standard dose rituximab for the treatment of antiphospholipid syndrome: A pilot study from a tertiary medical center

To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-β2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.

Significance of anti-HBc serological status in primary immune thrombocytopenia.

The association of previous hepatitis B virus (HBV) exposure [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc/HBcAb) positive] with disease severity and decision on treatment option in primary immune thrombocytopenia (ITP) patients remains unclear. Data from 725 patients diagnosed with ITP were analyzed to elucidate the association between anti-HBc serological status and disease severity. Data from a published prospective study [high-dose dexamethasone (HD-DXM), HD-DXM plus recombinant human thrombopoietin, NCT01734044] and two retrospective studies (standard-dose and low-dose rituximab) were rearranged to evaluate the impact of anti-HBc serological status on the response and outcome to ITP-specific treatments and the risk of HBV reactivation related to these treatments. The prevalence of HBsAg- HBcAb+ and HBsAg- HBcAb- in ITP patients was 51·03% and 48·97% respectively. Compared to the HBsAg- HBcAb- group, patients in the HBsAg- HBcAb+ group had lower platelet count, higher bleeding score, and longer hospitalization (P = 0·002, 0·033, and 0·008 respectively). Moreover, the initial complete response rate of HBsAg- HBcAb+ patients was lower than that of HBsAg- HBcAb- patients (45·2% vs 59·8%, P = 0·027). In conclusion, previous HBV exposure was correlated with disease severity and hospitalization in ITP patients. Anti-HBc positivity may be considered as a predictor for poor response to ITP-specific treatments.

Chronic Lymphocytic Leukemia (CLL) Clonal Growth Rate Is Slower Following Venetoclax-Rituximab (VenR): Results from a Minimal Residual Disease (MRD) Model from the Randomized Phase 3 Murano Trial

Chronic Lymphocytic Leukemia (CLL) Clonal Growth Rate Is Slower Following Venetoclax-Rituximab (VenR): Results from a Minimal Residual Disease (MRD) Model from the Randomized Phase 3 Murano Trial

The Efficacy and Safety of Different Dosages of Rituximab for Adults with Immune Thrombocytopenia: A Systematic Review and Meta-Analysis.

Background Rituximab has been frequently used as a second-line treatment for patients with immune thrombocytopenia (ITP). The optimal dose and course of rituximab are uncertain. Methods A comprehensive search for randomized controlled trials reporting the use of low-dose (100 mg) or standard-dose (375 mg/m2) rituximab in ITP treatment was conducted. Meta-analyses were performed on CRR (complete response rate), ORR (overall response rate), PRR (partial response rate), SRR (sustained response rate), infection rate, SB (significant bleeding) rate, and SAE (serious adverse event) rate. Results A total of 12 studies were included, comprising 869 patients. Compared to the control group, rituximab treatment resulted in an obvious increase in CRR (P < 0.00001), ORR (P < 0.0001), and SRR at month 6 and 12 (P = 0.0007, P = 0.0003), without increasing the infection rate (P = 0.12) and SAE rate (P = 0.11). No significant differences in CRR (RR 1.61 vs. 1.42, P = 0.45), ORR (RR 1.26 vs. 1.49, P = 0.28), PRR (RR 1.25 vs. 1.00, P = 0.11), SRR at month 12 (RR 2.00 vs. RR 1.64, P = 0.54), infection rate (RR 0.85 vs. 1.46, P = 0.36), and SB rate (RR 0.14 vs. 1.19, P = 0.17) were found in subgroups of low dose and standard dose. Conclusion Rituximab was effective and safe for adult patients with ITP. A low-dose rituximab regimen might be an effective alternative to the standard-dose regimen in ITP, as it showed similar CRR, ORR, and SRR at month 12 and was relatively safer with a lower cost.

Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma: 5-Year Follow-up and Correlative Analysis from a Multi-Center Phase II Study

Abstract BACKGROUND: We previously reported early results of a multicenter phase 2 study of lenalidomide plus rituximab as initial treatment for MCL (NEJM 2015:373:1835), which was highly effective (ORR 92%, CR 64%) and well tolerated. Here we present outcomes with 5-year follow-up, as well as exploratory analysis of immunologic biomarkers and minimal residual disease measurement. METHODS: The study includes both induction and maintenance. Lenalidomide was administered at 20 mg daily on days 1-21 of a 28-day cycle for 12 cycles during induction, followed by dose reduction to 15 mg during maintenance. Standard dose rituximab was administered weekly x 4 during cycle 1, then once every other cycle. Treatment was continuous until progression, with option to stop therapy after 3 years. Plasma samples were obtained at baseline, C2D1 and C4D1 to measure cytokines (IFN γ , IL10, IL12p70, IL12, IL1 β , IL2, IL4, IL6, IL8, TNF α) and chemokines (MCP1, MCP4, Eotaxin, IP10, MDC, Eotaxin3, TARC, MIP1 α , MIP1 β, IL8), using MesoScale Discovery V-plex assays. The cytokine/chemokine levels over time, and their associations with responses and treatment-emergent rash were analyzed with Wilcoxon signed-rank and rank-sum tests. MRD was assessed using ClonoSEQTM (Adaptive Biotechnologies, Seattle WA) on subjects with available paired pre-treatment tissue and post-induction PB samples. RESULTS: 38 subjects requiring therapy were enrolled at 4 centers from 7/2011 to 4/2014. The median age was 65 and MIPI scores evenly distributed between low-, intermediate-, and high-risk. Median follow-up was 58 months with range of 36-70 months. Two patients were inevaluable - one withdrew consent, other was intolerant of tumor flare. Twenty-two (61%) of the evaluable 36 patients remain in remission, including 13 (36%) beyond 5 years. Nineteen patients remain on treatment and 3 opted to stop therapy after 3 years. Eleven patients had progression - 3 with primary refractory disease and 8 following initial responses (4 CRs with PFS of 18, 38, 39 and 49 months, 4 PRs with PFS at 14, 25, 28 and 43 months). Six evaluable patients died, 3 from progression, 3 from unrelated comorbidities. Median PFS and DOR have not been reached. The 3-yr and 4-yr PFS rates were estimated at 80.3% (95% CI = 63.0%, 90.1%) and 69.7% (95% CI = 50.6%, 82.6%), with 3-yr and 4-yr OS rates at 91.9% (95% CI = 76.9%, 97.3%) and 82.6% (95% CI = 65.3%, 91.9%). TEAEs during maintenance included asymptomatic grade 3-4 cytopenias (42% neutropenia, 5% thrombocytopenia, 3% anemia), and grade 1-2 infections (45% URI, 16% UTI, 13% sinusitis and 8% cellulitis), all managed in outpatient settings. Five patients required brief hospitalization for IV antibiotics: 1 (3%) developed neutropenic fever in setting of cholecystitis, 3 (8%) had pneumonia and 1 (3%) had recurrent UTI. Secondary malignancies included squamous-cell carcinoma in 2 subjects, basal-cell carcinoma in 1 subject, and melanoma in situ in 2 subjects. Merkel-cell carcinoma developed in an 86-year-old subject after 18 months of therapy, and pancreatic cancer was diagnosed in a 68-year-old patient after 12 months of therapy. Compared to baseline, cytokine levels at C2D1 and C4D1 showed Th1/Th2 modulation, with significant increase in IFNγ (p=0.004 and p=0.007) and IL4 (p=0.004 and p=0.017), as well as significant decrease in IL2 (p=0.046 and p=0.032), IL10 (p=0.004 and p=0.007) and TNFα (p CONCLUSIONS: Lenalidomide and rituximab as initial treatment for MCL can achieve high rate of complete responses and MRD negativity with durable remissions beyond 4 years. The nature of toxicity was not significantly affected by continuous treatment, particularly in the context of close follow-up. Further evaluation of this active regimen in larger, randomized frontline trials is warranted (ClinicalTrials.gov - NCT01472562). Disclosures Ruan: Cell Medica: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Martin: Celgene: Consultancy; Janssen: Consultancy, Honoraria, Other: travel expenses; Teva: Research Funding; Novartis: Consultancy; Genentech: Consultancy; Gilead: Consultancy, Other: travel expenses. Cerchietti: Celgene: Research Funding; Lymphoma Research Foundation: Research Funding; Leukemia and Lymphoma Society: Research Funding; Weill Cornell Medicine - New York Presbyterian Hospital: Employment. Schuster: Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Nordic Nanovector: Consultancy; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Merck: Research Funding. Svoboda: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pharmacyclics: Research Funding; Kite: Consultancy; Merck: Research Funding; Celgene: Research Funding. Furman: Verastem: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Honoraria; TG Therapeutics: Consultancy; Abbvie: Consultancy, Honoraria; Gilead: Consultancy; Pharmacyclics: Consultancy, Honoraria; Sunesis: Consultancy. Leonard: Roche: Consultancy; Celgene: Consultancy, Research Funding.

Six month assessment of low dose rituximab in the treatment of rheumatoid arthritis during coronavirus disease 2019 (COVID-19) pandemic

Aim of the workTo evaluate the 6-month treatment responses to low dose rituximab (LDR) compared to standard dose rituximab (SDR) in rheumatoid arthritis (RA) patients whose treatments were disrupted due to the pandemic with increased disease activity and to examine the effect of LDR treatment on serum immunoglobulin (Ig) levels. Patients and methodsRecords were retrospectively analysed for 80 patients on SDR not admitted to the hospital due to fear of infection during pandemic, with increased disease activity and were resumed on LDR (500 mg intravenous RTX-infusion twice with 15 days intervals, and repeated for the second time in all patients after 6 months). Disease activity score (DAS-28) values were obtained. The Ig levels of the patients before and after rituximab treatment were calculated. ResultsThe mean age of patients was 55.1 ± 13.1 years. They were 46 (57.5%) female and 34 (42.5%) male (F:M 1.4:1) with median disease duration of 13 (0.5–50) years. After the second dose of LDR, there was a significant decrease in the disease activity DAS28 (6.5 ± 1.01 to 3.2 ± 1.2, p < 0.0001) and acute phase reactants with a tendency to decrease in Ig levels. After LDR, 6 (7.5%) patients developed COVID-19 infection that did not require hospitalization. There was no difference between the Ig levels of patients with and without COVID-19 infection. ConclusionsLDR is an effective treatment option in the treatment of RA. In our study, none of our patients developed severe COVID-19 infection requiring hospitalization, and LDR may be preferred during the COVID-19 pandemic period.

Comparison of low fixed dose versus standard-dose rituximab to treat thrombotic thrombocytopenic purpura in the acute phase and preemptively during remission

The standard dose of rituximab used in B-cell hematological malignancies, 375 mg/m2 weekly, may be excessive for autoimmune conditions. Successful use of a low, fixed dose of 100−200 mg of rituximab, weekly for 4 weeks, has been reported in the literature in the treatment of autoimmune thrombotic thrombocytopenic purpura (aTTP). We retrospectively analyzed our rituximab data in aTTP over a 13-year-period for 39 patients, with the aim of comparing response and outcomes with a standard lymphoma-dose course versus a low fixed 100 mg-dose course. Compared to the standard dose (17 patients, 17 courses of 4 infusions), our patients who received a low dose (8 patients, 9 courses of 4 infusions) had a possibly lower baseline risk but did achieve a similar time to remission and number of plasma exchange procedures to remission. Preemptive low-dose courses for ADAMTS13 activity <50 % during remission (6 patients, 10 courses of 4 infusions) achieved a median peak ADAMTS13 activity of 99 %, in a median of 1 month, with no clinical relapses. Our results provide additional evidence for the efficacy of low-dose rituximab, with the benefit of much lower cost, less infusion time, and theoretically lower risk of toxicity.

Comprehensive Geriatric Assessment (CGA): A Simple Tool for Guiding the Treatment of Older Adults with Diffuse Large B-Cell Lymphoma in China.

BackgroundWe aimed to validate a simple Comprehensive Geriatric Assessment (CGA) in older adults with diffuse large B‐cell lymphoma (DLBCL) in China and to evaluate the tolerability and efficacy of CGA‐driven therapy.Materials and MethodsIn total, 78 patients with DLBCL aged ≥60 years were evaluated using CGA with the following parameters: age ≥ 80 years, activities of daily living (ADL), instrumental ADL, and modified cumulative illness rating score for geriatrics. Patients were grouped as fit, unfit, or frail. Patients classified as fit received standard‐dose rituximab plus CHOP, whereas patients in the latter two groups received reduced‐dose or reduced‐agent therapy. The overall response rate (ORR), overall survival (OS), progression‐free survival (PFS), and toxicities in the three groups were evaluated.ResultsAccording to the CGA, 45 (57.5%) patients were classified as fit, 5 (6.4%) as unfit, and 28 (35.9%) as frail. The ORR was 82.1% (64/78) among all the patients, including 55 patients (70.6%) who achieved complete response and 9 patients (11.5%) who achieved partial response. In the fit and unfit + frail groups, it achieved 97.8% and 60.6%, respectively. In total, 26 (33.3%) patients (10/45 [22.2%] fit and 16/33 [48.5%] unfit + frail) showed disease progression or recurrence. The median follow‐up time was 18 months (range, 5–62). The 3‐year OS and PFS rates were 82% and 58%, respectively. There were no treatment‐related deaths.ConclusionA simple CGA in older adults with DLBCL may be an effective tool for guiding therapeutic strategies in China.Implications for PracticeDiffuse large B‐cell lymphoma (DLBCL) is the most common malignant lymphoma in older adults. The simple tool, Comprehensive Geriatric Assessment (CGA), is proved to be an effective method to identify older adults with DLBCL who are suitable for standard‐dose R‐CHOP regimen therapy. This is the first prospective trial in China to evaluate the tolerability and efficacy of CGA‐driven therapy for older adults with DLBCL, and the result showed that this simple CGA may be an effective tool for guiding therapeutic strategies.

P0381THE UTILITY OF LOW DOSE RITUXIMAB FOR INDUCTION AND MAINTENANCE TREATMENT IN ELDERLY PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: A SINGLE CENTRE EXPERIENCE

Abstract Background and Aims Elderly patients with Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) tend to have higher rates of mortality and treatment-related adverse events. Rituximab is now widely used in the treatment of patients with AAV based on the results of remission induction (RITUXVAS and RAVE) and remission maintenance (MAINRITSAN) randomized controlled trials. Elderly patients were relatively under-represented in these trials. In this observational study we aimed to examine the outcome of elderly patients who received Rituximab (either as low dose Rituximab (LDR) or standard dose Rituximab (SDR)) for remission induction and maintenance. Method We investigated the outcome of three treatment strategies in elderly (age&amp;gt;65 years) patients who presented with AAV to our Vasculitis clinic from 1 July 2007 to 9 of July 2017. These strategies included: LDR (17 patients), SDR (14 patients) and Cyclophosphamide/Azathioprine (Cyc/A) 26 patients. LDR patients received two dose of 500mg Rituximab fortnightly followed by six monthly 500mg doses for 2 years. SDR patients received 1g Rituximab fortnightly followed by six monthly 1g doses for 2 years. Cyc/A patients received 1.5mg/kg oral Cyclophosphamide for 3 months followed by 18 months of Azathioprine. Results Among 57 AAV patients, 56% were females and mean age of 79.6 +/- 4 (LDR), 72.4 +/- 7.2 (SDR), and 71.1 +/- 5 (Cyc/A) (p=0.001). The distribution of MPA and GPA was 11/6 in LDR, 7/7 in SDR and 18/8 in Cyc, respectively. Relapsing GPA was significantly higher in SDR 12/2 compared to LDR 3/14, and Cyc/A 0/26 (p=0.0001). There were no significant differences in serum creatinine, BVAS scores or CRP between groups at initiation of treatment. Patients survival at 24 months was 88% (LDR), 92% (SDR), and 77% (Cyc), p=0.3. The mean corticosteroids dose at 3 months from onset of treatment was significantly lower in the LDR (7.6 +/- 1.7) and SDR (8.6 +/- 3.1) compared with Cyc/A (12.5 +/- 3.6), p=0.001. 1 patients relapsed in the SDR group and 4 patients in the Cyc/A group. Hospitalization for infections were significantly lower in the LDR (3 episodes) compared to Cyc/A (17 episodes), p=0.004. The number of patients with hypogammaglobulinemia was not significantly different between LDR and SDR. Conclusion In this single centre observational study, we found that low dose Rituximab for remission induction and maintenance associated with similar patient outcome to SDR. The findings of this study needs to be replicated with longer duration of follow-up.

Ultra-low doses of rituximab for continued treatment of rheumatoid arthritis (REDO study): a randomised controlled non-inferiority trial.

Rituximab is an effective treatment for rheumatoid arthritis, given as either two doses of 1000 mg (2 weeks apart) every 6 months (the dose recommended by the US Food and Drug Administration and European Medicines Agency) or two doses of 500 mg (2 weeks apart) or one dose of 1000 mg (a standard low dose) every 6 months. Findings of several small uncontrolled studies suggest that doses lower than the recommended dose or standard low dose might be sufficient for maintenance treatment, potentially improving safety and reducing costs. Therefore, we aimed to compare the efficacy of ultra-low doses of rituximab (one dose of 500 mg or 200 mg) with a standard low dose of rituximab (one dose of 1000 mg) for patients with rheumatoid arthritis who respond to standard doses of rituximab. The REDO study is a randomised, double-blind, non-inferiority trial done at five centres in the Netherlands. Adults (aged ≥18 years) with rheumatoid arthritis responding well to rituximab were randomly allocated (1:2:2) to receive intravenous rituximab as one dose of either 1000 mg, 500 mg, or 200 mg, respectively. Volumes of all doses were equal to achieve masking. Randomisation lists were computer-generated and stratified by rheumatoid factor or anti-citrullinated protein antibody status (positive or negative) and concomitant use of conventional synthetic disease modifying antirheumatic drugs (yes or no). The primary analysis was a per-protocol hierarchical testing procedure comparing ultra-low doses with a standard low dose (500 mg vs 1000 mg at 3 months, followed by 500 mg vs 1000 mg at 6 months, 200 mg vs 1000 mg at 3 months, and 200 mg vs 1000 mg at 6 months), using a non-inferiority margin of 0·60 on change from baseline in the 28-joint disease activity score based on C-reactive protein levels (DAS28-CRP). The study is registered at www.trialregister.nl, NTR6117. Between Dec 15, 2016, and Sept 20, 2018, 142 patients were randomly allocated to either 1000 mg rituximab (n=29), 500 mg rituximab (n=58), or 200 mg rituximab (n=55). The 500 mg dose was non-inferior to 1000 mg at 3 months (mean change from baseline in DAS28-CRP, -0·07, 95% CI -0·41 to 0·27) but not at 6 months (0·29, -0·08 to 0·65). Because of the hierarchical testing procedure, non-inferiority could not be tested for the 200 mg dose. 13 patients had serious adverse events, three (10%) in the 1000 mg group, six (10%) in the 500 mg group, and four (7%) in the 200 mg group. The most frequently reported serious adverse events were cardiovascular. No deaths occurred during the study. A significantly lower incidence of infections was seen in the ultra-low-dose groups compared with the standard dose group (1·10 infections per patient-year with the 1000 mg dose vs 0·52 per patient-year with the 500 mg dose and 0·51 per patient-year with the 200 mg dose; rate ratio 0·47, 95% CI 0·21-0·83; p=0·013 for 500 mg vs 1000 mg; 0·44, 0·22-0·88; p=0·019 for 200 mg vs 1000 mg). Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. Nonetheless, in clinical practice, a strategy with an ultra-low dose of rituximab might be considered after evaluation of risks and benefits, although further studies are needed to establish non-inferiority. Further analyses and a 2-year observational extension are ongoing and should provide further insight into efficacy and safety. Menzis and Centraal Ziekenfonds.

Lymphoid Interstitial Pneumonia in Common Variable Immune Deficiency - Case Report With Disease Monitoring in Various Therapeutic Options: Pleiotropic Effects of Rituximab Regimens.

Lymphoid interstitial pneumonia (LIP) is a rare lymphoproliferative disease. LIP in common variable immunodeficiency (CVID) was observed in a patient during immunomodulatory therapy after progression of the disease (i.e., glucocorticoids, immunoglobulin dose escalation, and finally rituximab). Due to humoral immunodeficiency and serious serum sickness rituximab was used initially at a low dose (150 mg/m2 weekly). It resulted in temporary remission with the decrease of serum paraproteinemia, β2-microglobulin (β2M) and SUV decrease as well as increase of FVC. Owing to the relapse after 6-month remission in the second cycle a standard dose of rituximab was used (375 mg/m2). Therapeutic regimen with 375 mg/m2 of Rtx in optimal schedule (i.e., every 3 weeks) resulted in no longer remission but higher incidence of opportunistic infections. Finally, after another cycle of immunotherapy FVC, paraproteinemia and β2M level normalization were observed as well as the decrease of severe splenomegaly. In laboratory and immunological progress the increase of NK and NKT cells was observed after the initial dose but the standard one caused NK cell increase only. Unfortunately, the decrease of CD19+Bcells was comparable between both doses, as was the decline of FoxP3+ regulatory T cell. On the contrary, after the low dose absolute T cell (both CD4 and CD8) number decreased but after the standard one – it normalized. Rtx (especially in low dose) brought further increase of persistent T cell activation (CD38+ T cells made up 79%). Innate immune response and the decrease of Treg are a compensatory pathways for the decrease of B and T cells. Immunodeficiency requires a different investigative approach to a immunotherapy.Clinical Trial Registration: ClinicalTrials.gov, NCT02789397.

Clinical Efficacy and Safety of High-Dose Dexamethasone Plus Low-Dose Rituximab as First-Line Therapy in Newly Diagnosed Primary Immune Thrombocytopenia.

Standard-dose prednisone as first-line therapy for primary immune thrombocytopenia (ITP) can not obtain high long-term responses. Results from high-dose dexamethasone course administered in adult newly diagnosed ITP were promising. The role of standard-dose rituximab in first-line treatment of newly diagnosed ITP were also investigated. We retrospectively analyzed the efficacy and safety of high-dose dexamethasone plus low-dose (100mg/w) rituximab for treatment of adults newly diagnosed ITP. A total of eighteen patients received dexamethasone 40mg/day for 4 consecutive days (days + 1 to + 4), rituximab 100mg once weekly for a total of 4weeks (days + 7, + 14, + 21 and + 28). Non-responders accepted the repeated dexamethasone treatment every 2weeks for a total of up to 3 treatment cycles. The overall response was 100% at 28th day. Median follow-up was 17months (1-33months). Six patients (33.3%) relapsed. Sustained complete response or response after 6months and 12months of follow-up were reached in 83.3% (15/18) and 61.5% (8/13) of patients respectively. The 12-month and 15-month cumulative relapse-free survival were 69.3% and 60.7%. Incidence of adverse effects was 11.1% (2/18). High-dose dexamethasone plus low-dose rituximab therapy had high efficacy and well tolerability as first-line treatment option in newly diagnosed ITP.

Cost Effectiveness of Rituximab As Adjunctive Therapy in Reducing Apheresis Procedures and Hospital Length of Stay in Relapsed Thrombotic Thrombocytopenic Purpura

Introduction: Rituximab at standard dosing (375 mg/m2 weekly for 4 weeks) is effective in preventing thrombotic thrombocytopenic purpura (TTP) relapse and is recommended as a therapy of choice along with plasmapheresis (PLEX) in the UK expert-based guidelines on TTP (category IB), although it is not yet universally viewed as standard of care. There is also emerging data for low dose rituximab (100 mg weekly for 4 weeks) in the treatment of relapsing TTP with mixed data on efficacy as compared to standard dose rituximab. With this in mind, we conducted a retrospective chart review to examine the financial cost of treating a patient hospitalized for a TTP relapse with rituximab, PLEX and steroids compared to PLEX and steroids only. The purpose of this study was to determine an average savings per patient of utilizing rituximab as an adjunctive agent in the inpatient setting.Methods: Chart records for patients admitted to a major academic center with a diagnosis of TTP, defined as laboratory and smear evidence of microangiopathy with ADAMTS13 level of 10% or less or evidence of microangiopathy in a patient with a prior established diagnosis of TTP, were reviewed. The clinical course of all patients including treatments received and length of stay (LOS) for each hospitalization was recorded. TTP relapse was defined as hospitalization for TTP more than 30 days after hospital discharge. An average hospital cost per patient with a relapsed episode of TTP was calculated utilizing average costs for LOS and for PLEX during their hospitalization for TTP relapse. The average wholesale price of a fixed dose of rituximab for one cycle (defined as four doses of 375 mg/m2) was utilized to calculate the total cost of rituximab treatment. A cost superiority determination per patient was calculated by comparing the total cost of relapsed TTP hospitalizations versus the cost of rituximab administered in the inpatient setting. All costs are listed in United States Dollar (USD).Results: A total of 28 patients spanning 25 years were hospitalized for a TTP exacerbation. The median age of these patients was 40.7 with ADAMTS13 level of 6.5% at diagnosis and 3.2% at relapse. Of 28 patients, 15 patients had relapsed TTP for a total of 50 hospitalizations. All 15 relapsed patients were treated with PLEX and steroids during every hospitalization. The average number of inpatient PLEX procedures performed on patients admitted for relapsed TTP was 7.1 with an average hospital LOS of 9.6 days. 13 of the 15 relapsed patients received a total of 15 cycles of rituximab while 2 patients did not receive any rituximab. Of the 13 rituximab-treated patients, 10 received one cycle of rituximab, with 9 achieving a sustained remission and the other patient experiencing a relapse of TTP that was not treated with any additional rituximab; 2 received a second cycle, with both achieving a sustained remission, although 1 had an allergic reaction during the second cycle that led to discontinuation of rituximab. In total, 11 of 15 episodes of relapsed TTP were treated with rituximab with 73% achieving a sustained remission over a median follow up time of 36 months.In our study cohort, use of rituximab would have led to a reduction in 182 total hospitalization days and 135 total PLEX procedures, yielding a cost savings of $59,918.40 per relapse of TTP. This would be offset by a cost of $30,894 for each cycle of standard dose rituximab, for a net cost savings of $29,024.40 per occurrence of TTP relapse treated with rituximab. A similar cost analysis utilizing low dose rituximab yielded a net cost savings of $55,582.40 per relapse of TTP, assuming similar efficacy of low and standard dose rituximab.Conclusions: The addition of rituximab to PLEX and steroids in treatment of relapsed TTP is more cost effective than PLEX and steroids alone, owing to the high efficacy of rituximab and the cumulative costs of PLEX and hospital LOS. This cost superiority of rituximab holds both for standard and low dose rituximab, assuming similar efficacy of the latter. Although not calculated in our analysis, administration of rituximab in the outpatient rather than inpatient setting would result in further cost savings. Therefore, from a cost efficiency standpoint, rituximab should be incorporated into treatment paradigms for relapsed TTP. DisclosuresNo relevant conflicts of interest to declare.

Efficacy of Adjuvant Low Dose Rituximab and Plasma Exchange for Acquired TTP with Severe ADAMTS13 Deficiency — Results of the ART Study

▪Introduction:Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13 that prevent the cleavage of von Willebrand factor and allow the growth of microvascular thrombi, causing microangiopathic hemolysis and severe thrombocytopenia. Untreated TTP is almost always fatal but plasma exchange enables ~80% of patients to survive. Those who respond often have exacerbations or relapses that require more therapy. Exacerbations and refractory TTP usually can be treated effectively by combining plasma exchange, corticosteroids, and rituximab. A typical regimen for TTP is 4 weekly doses of rituximab 375 mg/m2, which is borrowed from protocols for B cell lymphomas. However, the pathogenic B cell mass in TTP is much less than in lymphoma and lower doses of rituximab may be enough. For example, case reports in TTP and studies in immune thrombocytopenia suggest that fixed doses of 100 mg and conventional doses of 375 mg/m2 have similar efficacy.Methods:The ART study (Adjuvant Rituximab in TTP, NCT01554514) was designed as a pilot safety/efficacy study of low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for TTP. The study enrolled at Washington University, Beth-Israel Deaconess Medical Center, Emory University, and Duke University. Eligibility criteria include age ≥18 years with acute TTP and ADAMTS13 <10%. Exclusions include treatment for TTP within 2 months, severe infection, cancer, organ or stem cell transplant, pregnancy, hepatitis B, and use of calcineurin inhibitors within 6 months or rituximab within the past year. Treatment included daily 1.5 volume plasma exchanges, prednisone 1 mg/kg, and rituximab 100 mg weekly for 4 doses starting before the 5thplasma exchange. Treatment Response is defined as 2 consecutive days with a platelet count ≥150,000/µl. A Durable Treatment Response persists ≥30 days after stopping plasma exchange. The primary endpoint is a composite of Exacerbation or Refractory TTP, where Exacerbation is recurrence of TTP ≤30 days after a treatment response and Refractory TTP is failure to achieve a Treatment Response by day 28 or failure to achieve a Durable Treatment Response by day 60.Secondary endpoints include the relapse rate at 2 years.Results:19 patients were enrolled. Two patients were subsequently excluded: 1 proved to have congenital TTP and was ineligible, 1 was withdrawn for protocol violations during the first week. The 17 evaluable patients have a median age of 48 years (range 30-71), 14 (82%) are African-American and 11 (65%) are female. All had a treatment response in a median of 5 days (range 3-16 days). 13 patients achieved normal ADAMTS13 levels after treatment, 2 had persistent severe ADAMTS13 deficiency, and 2 patients have yet to be assessed for ADAMTS13 responses. No patients had refractory disease and 2 had exacerbations; both achieved Durable Treatment Responses after 29 and 35 days. No patient died of TTP; 1 patient died of metastatic cancer. To date, 13 patients have completed 2 years of follow up and 3 (23%)have relapsed at 11, 19, and 22 months. For comparison, among 54 episodes of TTP at Washington University treated without rituximab, the primary endpoint occurred in 26 (48%). These included exacerbation in 23 (43%), refractory disease in 9 (17%), and both in 6 (11%). 6 patients died, and the incidence of relapse within 2 years was 51%. Treatment with low dose rituximab (100 mg) was associated with a significant decrease in the primary endpoint from 48% to 12% (P= 0.01, Fisher's exact test) and an encouraging decrease in 2-year relapse rate from 51% to 23% (P= 0.06).Conclusions:These results with low dose rituximab (100 mg x 4 doses) are consistent with reports that immediate treatment of TTP with standard dose rituximab (375 mg/m2x 4 doses) reduces the incidence of exacerbation and refractory disease, and prevents or delays relapses. A direct comparison of these regimens would be useful to establish whether low dose rituximab has similar efficacy with greater ease of administration, less cost, and less risk of infusion reactions and late complications. DisclosuresSadler:Ablynx: Consultancy. Zwicker:Quercegen: Research Funding; Daiichi: Honoraria; Parexel: Consultancy; Incyte: Research Funding.

Results of a Phase II of Low-Dose Fludarabine and Cyclophosphamide Combined with Standard Dose Rituximab (FCR-LITE) in Elderly, Untreated Patients with Chronic Lymphocytic Leukemia (CLL): The Israeli CLL Study Group Experience

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients.Despite the development of novel agents and new monoclonal antibodies, FCR still remains the combination chemoimmunotherapy of choice for fit patients with CLL, yielding the longest durations of remission.When this study was first started, no established chemo-immunotherapy regimen was unanimously regarded as standard therapy for less fit elderly patients with CLL; this category of patients had clearly been underrepresented in clinical trials utilizing chemo - or chemo-immunotherapy.Patients and MethodsWe conducted a single arm, phase II trial to assess the efficacy and toxicity of low dose fludarabine and cyclophosphamide in combination with a regular dose of rituximab (FCR-LITE) in elderly patients with therapy naïve CLL. Our intention was to deliver 6 courses of Fludarabine which was given intravenously (IV) at 12.5 mg/m2/day together with IV cyclophosphamide 150 mg/m2/day for 3 consecutive days. IV rituximab was administered on day 0 of cycle 1 at a dose of 375 mg/m2, and at 500 mg/m2 on day 1 of cycles 2-6.Categorical variables were compared in patients with and without CR using chi-square test or Fisher's exact test and continuous variables were also compared using Mann Whitney test. Duration of follow-up was recorded using reverse censoring method. Kaplan Meier curve was used to establish PFS during clinical follow-up.All statistical tests were two sided. P<0.05 was considered as statistically significant.ResultsForty patients treated with FCR-LITE were included in the efficacy analysis.The median age of the entire cohort was 72.7 years (range, 65.0 to 85.0), and 69% were male. The mean number of treatment cycles was 5.1 (range 1-6).The overall response rate was 67.5% (95% CI, 50.9%-81.4%); 17 patients (42.5%) achieved CR and 10 (25.0%) PR.Median PFS was 35.5 months (95% CI, 29.27-41.67). Two patients (4.8%) died during the study period.Reduced cumulative doses of FCR and fewer courses of treatment were both associated with lower CR rate.Hematological toxicities were the most common side effects encountered; grade-3/4 neutropenia occurred in twenty (47.6%) patients, only six (14.3%) developed neutropenic fever. Positive direct antiglobulin test (DAT), was seen in 11 patients but none of them developed autoimmune hemolytic anemia (AIHA) during treatment; two patients (4.8%) progressed to Richter's transformation and two (4.8%) had second malignancies (lung and metastatic colon carcinoma).ConclusionFCR-LITE is effective and safe for treating elderly patients with therapy-naïve CLL. It has the advantage of being both time and cost effective. In an era of novel agents, it can still be considered as suitable frontline treatment for fit elderly patients with CLL.This research was supported by roche pharmaceuticals DisclosuresTadmor:ABBVIE: Consultancy; ROCHE: Research Funding; NOVARTIS: Consultancy; JNJ: Consultancy; PFIEZER: Consultancy. Herishanu:JNJ: Consultancy; ABBVIE: Consultancy; ROCHE: Research Funding. Bairey:ROCHE: Research Funding; AbbVie: Consultancy; Jansen: Research Funding. Aviv:ABBVIE: Consultancy; ROCHE: Research Funding. Rahimi-Levene:ABBVIE: Consultancy. Fineman:ABBVIE: Consultancy; JNJ: Consultancy. Ruchlemer:JNJ: Consultancy; ABBVIE: Consultancy. Shvidel:JNJ: Consultancy; ROCHE: Consultancy, Research Funding; ABBVIE: Consultancy, Research Funding. Polliack:ABBVIE: Consultancy; ROCHE: Research Funding.

Ibrutinib, Bendamustine, Rituximab Combination for Relapsed and Refractory Aggressive B Cell Lymphoma — Interim Analysis of Phase II Clinical Trial

Background: Ibrutinib is an orally-administered inhibitor of Bruton's tyrosine kinase. It is an effective agent in diffuse large B cell lymphoma (DLBCL), specifically of the Activated (ABC) type (Younes A et al, Lancet Oncol 2014). The combination of ibrutinib, bendamustine, and rituximab (IBR) was reported to be potent for B cell lymphomas, including DLBCL, in a phase I clinical trial (Maddocks et al, Blood 2015). We aimed to explore the efficacy of the IBR regimen in patients with relapsed & refractory (RR) aggressive B cell lymphoma (ABCL), who were either transplant ineligible or in relapse post autologous stem cell transplantation (ASCT). We report here, the interim analysis of a phase II clinical trial.Methods: Patients with RR ABCL of all subtypes as well as transformed low-grade lymphoma and grade 3B follicular lymphoma were eligible. Patients with CNS lymphoma, inadequate bone marrow function or previous exposure to bendamustine or ibrutinib were excluded. All diagnostic biopsies were centrally reviewed or repeated. PET scans were interpreted according to the Lugano criteria 2014. Rituximab and bendamustine were given for a six 28 days cycles in their standard dose (rituximab 375 mg/m2 in day 1 and bendamustine 90/70 mg/m2 day 1 and 2). Ibrutinib 560 mg orally, was administered continuously from day 1. PET scans were repeated after 3 and 6 cycles of therapy and then every 16 weeks up to 3 years. Patients that achieved a response after 3 cycles and who were eligible, could undergo either allogeneic or autologous stem cell transplantation. For the interim analysis, 34 patients were screened, and 32 of them were treated.Results: Seventeen male (53%) and 15 (47%) female patients, median age 69 (28-94) were treated. All patients received at least one prior line of rituximab-containing therapy mostly RCHOP (n=28, 87%). Ten (31%) participants received the IBR therapy as a second line and 22 (69%) as a third-line regimen, 6 (19%) received prior ASCT. Eight (25%) patients had relapsed disease, and 24 (75%) were refractory. Twenty-nine patients had denovo aggressive B cell lymphoma, including 12 (37%) ABC-DLBCL, 5 (16%) GCB-DLBCL, 6 (19%) undefined DLBCL, 2 (6%) primary mediastinal lymphoma and 4 (12%) double hit high grade lymphoma. Two patients had transformed low grade and 1 grade 3B follicular lymphoma.We recorded 258 adverse events (AEs); 11 (4%) were Serious Adverse Events (SAEs) and 3 (1%) adverse events were of particular interest. SAEs that were related to ibrutinib were documented in 4 patients one time each (1.6%) and included atrial flutter/fibrillation, fatigue, and thrombopenia.Of the 32 patients 27 were evaluable for response, the additional 5 patients had early clinical progression. Complete response (CR) was documented in 8 (30%), partial response in 4 (15%) and stable disease in 2 (7%) translating to overall response rate (ORR) of 45%. On an intention to treat analysis ORR was 38%. There were no statistically significant differences in response rates between relapsed vs. refractory patients as well as ABC type vs. others.Four patients were referred to transplant after achieving CR or PR, 2 to ASCT and 2 to allogeneic stem cell transplantation. With a median follow-up of 14 months, all 4 patients remained alive and in remission. Median PFS and OS for the entire cohort (n=32) was 2.7 and 7.1 months, respectively. Both PFS and OS were significantly better for patients who achieved CR. Median PFS for patients with no CR was 2.5 months and was significantly different from patients with CR (p=0.008, log-rank test, figure 1a). Median OS for patients without a CR was 5.9 months; no deaths occurred among patients who achieved CR (p=0.032, log-rank test, figure 1b).There were no significant differences in OS or PFS between relapsed and refractory patients as well as between the different histological subtypes.Conclusions: We demonstrated that the IBR regimen is both safe and effective for patients with RR ABCL. Our patient population was of advanced age and mostly refractory, and despite that, we were able to show 45% ORR. Four of the patients that were chemorefractory and therefore transplant ineligible were able to undergo transplants after achieving remissions with this regimen, all of them are alive and in remission. We conclude that this regimen has promising results as a salvage regimen for RR ABCL patients both as a sole therapy or as a bridge to transplant, and it should be investigated in further clinical trials. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of rituximab dose on hepatitis B reactivation in patients with resolved infection undergoing immunologic incompatible kidney transplantation

Sensitized patients received desensitization therapy with rituximab for kidney transplantation. However, the impact of rituximab dose on hepatitis B virus (HBV) reactivation is unknown. Patients who underwent living donor kidney transplantation between 2008 and 2016 were grouped according to rituximab dose (control vs. standard-dose rituximab [375 mg/m2] vs. reduced-dose rituximab [200 mg/body]) for comparison of HBV reactivation. A total of 336 hepatitis B surface antigen (HBsAg)-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients underwent kidney transplantation, of whom 91 (27.1%) received rituximab for desensitization (57 standard-dose and 34 reduced-dose rituximab). During the study period, eight patients experienced HBV reactivation (three in the control group, five in the standard-dose group). In the standard-dose group, four patients experienced hepatitis flare, and one patient died due to hepatic failure. No HBV reactivation occurred in the reduced-dose group. Standard-dose rituximab significantly decreased hepatitis B surface antigen antibody titer (anti-HBs; −99.8 IU/L) at 12 months, compared with reduced-dose rituximab (−20.1 IU/L) and control (−39.1 IU/L, P = 0.017). Standard-dose rituximab (HR, 10.60; 95% CI, 2.52–44.60; P = 0.001) and anti-HBs < 100 IU/L at transplantation (HR, 9.06; 95% CI, 1.11–74.30; P = 0.04) were independent risk factors for HBV reactivation. Standard-dose rituximab significantly increased HBV reactivation risk for HBsAg-negative/anti-HBc-positive kidney transplant patients.