rituximab
Regulatory sources consulted
Approved indications
- In adults, CD20-positive B-cell non-Hodgkin lymphoma: relapsed or refractory follicular or low-grade disease, initial treatment and maintenance according to response, and diffuse large B-cell lymphoma with chemotherapy.
- In adults, untreated or previously treated CD20-positive chronic lymphocytic leukemia with fludarabine and cyclophosphamide.
- Moderate to severe active rheumatoid arthritis in adults, with methotrexate, after an inadequate response to one or more TNF antagonists.
- Active granulomatosis with polyangiitis or microscopic polyangiitis in adults, in combination with glucocorticoids.
- Moderate to severe pemphigus vulgaris in adults, in combination with a tapering glucocorticoid regimen.
Clinical warnings
- Boxed warning · It can cause fatal infusion-related reactions within the first 24 hours; about 80% of fatal reactions occurred with the first infusion. Monitor and discontinue the infusion for a severe reaction. — DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085f
- Boxed warning · It can cause severe and fatal mucocutaneous reactions. Discontinue for a severe reaction and arrange urgent assessment. — DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085f
- Boxed warning · It can reactivate hepatitis B virus and cause fulminant hepatitis, liver failure, or death. Screen for HBV before treatment and monitor during and after treatment according to risk. — DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085f
- Boxed warning · It can cause fatal progressive multifocal leukoencephalopathy. Discontinue and immediately investigate any new or progressive neurologic deficit. — DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085f
- Major warning · Tumor lysis syndrome, serious or fatal infections, cardiovascular and renal toxicity, and bowel obstruction or perforation have been reported. Identify risk, monitor, and treat early. — DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085f
Drug interactions
- LowFludarabine and cyclophosphamide
Mechanism: In patients with CLL, rituximab did not alter their systemic exposure.
Recommendation: Use according to the CLL protocol and monitor combined toxicity.
DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085fhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da1c4de7-0e5b-4f72-97ec-7a8d368f085f
- LowMethotrexate or cyclophosphamide in rheumatoid arthritis
Mechanism: Concomitant administration did not alter rituximab pharmacokinetics.
Recommendation: Use according to the protocol and monitor cumulative immunosuppressive toxicity.
DailyMed, RIABNI set_id da1c4de7-0e5b-4f72-97ec-7a8d368f085fhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da1c4de7-0e5b-4f72-97ec-7a8d368f085f
Adverse events
Common (≥1%)
infusion-related reactions · infections · neutropenia · lymphopenia · fever · chills · fatigue · nausea
Rare but serious
fatal infusion reaction · severe mucocutaneous reaction · hepatitis B virus reactivation · progressive multifocal leukoencephalopathy · tumor lysis syndrome · serious or fatal infection · renal toxicity · bowel perforation
Recent literature (PubMed)
The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival (PFS), but without improvement in overall survival (OS), likely because of toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL. Patients 65 years and older with previously untreated MCL received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus six cycles of bendamustine (90 mg/m2 once daily; days 1 and 2) and rituximab (375 mg/m2 as a single dose; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. The primary end point was PFS per the independent review committee; overall response rate and OS were secondary end points. In total, 598 patients were randomly assigned, with 299 in each arm. At a median follow-up of 49.8 months using the reverse Kaplan-Meier method, the median PFS was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.94]; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. OS was not significantly different (HR, 0.86 [95% CI, 0.65 to 1.13]; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively. The combination of acalabrutinib with bendamustine-rituximab significantly improved PFS. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.
Rituximab is a chimeric anti-CD20 monoclonal antibody that targets CD20-expressing B lymphocytes, has a well-defined efficacy and safety profile, and is broadly used to treat a wide array of diseases. In this review, we cover the mechanism of action of rituximab and focus on hypogammaglobulinemia and late-onset neutropenia-2 immune effects secondary to rituximab-and subsequent infection. We review risk factors and highlight key considerations for immunologic monitoring and clinical management of rituximab-induced secondary immune deficiencies. In patients treated with rituximab, monitoring for hypogammaglobulinemia and infections may help to identify the subset of patients at high risk for developing poor B cell reconstitution, subsequent infections, and adverse complications. These patients may benefit from early interventions such as vaccination, antibacterial prophylaxis, and immunoglobulin replacement therapy. Systematic evaluation of immunoglobulin levels and peripheral B cell counts by flow cytometry, both at baseline and periodically after therapy, is recommended for monitoring. In addition, in those patients with prolonged hypogammaglobulinemia and increased infections after rituximab use, immunologic evaluation for inborn errors of immunity may be warranted to further risk stratification, increase monitoring, and assist in therapeutic decision-making. As the immunologic effects of rituximab are further elucidated, personalized approaches to minimize the risk of adverse reactions while maximizing benefit will allow for improved care of patients with decreased morbidity and mortality.
Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10-4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to
Rituximab is an established therapy in children with idiopathic nephrotic syndrome to sustain short- to medium-term disease remission and avoid steroid toxicities. Recent trials focus on its use as a first-line agent among those with milder disease severity. Rituximab is used in multidrug refractory nephrotic syndrome and post-transplant disease recurrence, although the evidence is much less substantial. Available data suggest that the treatment response to rituximab depends on various patient factors, dosing regimen, and the concomitant use of maintenance immunosuppression. After repeated treatments, patients are found to have an improving response overall with a longer relapse-free period. The drug effect, however, is not permanent, and 80% of patients eventually relapse and many will require an additional course of rituximab. This underpins the importance of understanding the long-term safety profile on repeated treatments. Although rituximab appears to be generally safe, there are concerns about long-term hypogammaglobulinemia, especially in young children. Reliable immunophenotyping and biomarkers are yet to be discovered to predict treatment success, risk of both rare and severe side effects, e.g. , persistent hypogammaglobulinemia, and guiding of redosing strategy. In this review, we highlight recent advances in the use of rituximab for childhood nephrotic syndrome and how the therapeutic landscape is evolving.
Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab is used as rescue therapy. In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary end-points included progression-free survival (PFS) up to 6 months and safety. Between January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se 1.13) in the rituximab+MMF group and -2.01 (se 1.17) in the placebo+MMF group (between-group difference 3.60, 95% CI 0.41-6.80; p=0.0273). PFS was better in the rituximab+MMF group (crude hazard ratio 0.47, 95% CI 0.23-0.96; p=0.03). Serious adverse events occurred in 26 (41%) patients of the rituximab+MMF group and in 23 (39%) of the placebo+MMF group. Nine infections were reported in the rituximab+MMF group (five bacterial infections, three viral infections, one other) and four bacterial infections in the placebo+MMF group. Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection.