Dataset Information

Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study.

ABSTRACT:

Background

Interleukin (IL)-6 is one of the key cytokines in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH); however, the efficacy and safety of tocilizumab (TCZ), a monoclonal IL-6 receptor antibody, in patients with sHLH is uncertain.

Methods/results

This study included 64 adult patients who were diagnosed with sHLH based on the HLH-2004 criteria. Patients were classified into two groups based on treatment regimen at baseline: tocilizumab (TCZ group, n = 8) versus other treatments (control group), including HLH-2004 protocol (n = 35), chemotherapy (n = 7), glucocorticoid alone (n = 8), and with other immunosuppressants (n = 6). Primary outcome was overall 8-week survival. Baseline characteristics between the two groups were comparable. At day 56, one patient (12.5%) in the TCZ group and twenty-eight patients (51.9%) in the control group survived. Univariable and multivariable Cox proportional hazard analysis showed that TCZ significantly increased the risk of death (adjusted hazard ratio 5.55; 95% CI 2.13-14.49). The complete or partial response rate at day 14 was 44.6% in the control group, and nil in the TCZ group. In contrast, infectious complications occurred more frequently in the TCZ group than in the control group (14.3% vs. 50.0%).

Conclusion

Our results suggest that tocilizumab has limited efficacy in treating adult patients with sHLH and could increase the risk of infectious complications compared to the conventional treatments.

SUBMITTER: Kim JY

PROVIDER: S-EPMC9490693 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study.

Kim Ju Yeon JY Kim Miso M Park Jin Kyun JK Lee Eun Bong EB Park Jun Won JW Hong Junshik J

Orphanet journal of rare diseases 20220921 1

<h4>Background</h4>Interleukin (IL)-6 is one of the key cytokines in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH); however, the efficacy and safety of tocilizumab (TCZ), a monoclonal IL-6 receptor antibody, in patients with sHLH is uncertain.<h4>Methods/results</h4>This study included 64 adult patients who were diagnosed with sHLH based on the HLH-2004 criteria. Patients were classified into two groups based on treatment regimen at baseline: tocilizumab (TCZ group, n = ...[more]

PMID: 36131317

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Project description:Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors in patients with secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved a complete response by 4 weeks were defined as early stable responders, those who failed to achieve a complete response but showed continuous improvement until 8 weeks were defined as late responders, and those whose conditions waxed and waned until 8 weeks were defined as unstable responders. Patients with hemophagocytic lymphohistiocytosis caused by Epstein-Barr virus had a worse 5-year overall survival compared to those whose disease was secondary to autoimmune disease, other infections, or unknown causes (25.1% versus 82.4%, 78.7% and 55.5%, respectively; P<0.001). We observed that the overall response rate at 4 weeks was similar, but decreased at 8 weeks in the Epstein-Barr virus subgroup from 75.5% to 51.0%, and finally decreased to 30.6%. Multivariate analysis revealed that 8-week treatment response was the most relevant factor for overall survival. Excluding 8-week response, the presence of Epstein-Barr virus, old age, hyperferritinemia, and thrombocytopenia were associated with poor survival. We established a prognostic model with the parameters: low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score ≥3). These groups had 5-year overall survival rates of 92.1%, 36.8%, and 18.0%, respectively (P<0.001). We found that 8-week treatment response was a good predictor for overall survival, and that Epstein-Barr virus, old age, thrombocytopenia, and hyperferritinemia were associated with poor survival outcomes. Physicians should take care to identify high-risk patients for appropriate treatment strategies.

Project description:Hemophagocytic lymphohistiocytosis (HLH) is a fatal systemic inflammatory syndrome. HLH has been reported as a rare immune-related adverse event (irAE) in patients receiving immunotherapy with nivolumab, ipilimumab, and/or pembrolizumab. The data are limited to case reports and case series. The objective of this research is to compile data on this rare but potentially life-threatening adverse event of immune checkpoint inhibitors (ICIs) and identify the common agents that cause this irAE, clinical spectrum, and successful management strategies to assist the treating oncologists. A review was done using PubMed database. Eligible articles included case reports and case series published from January 1, 2015, through February 1, 2021. Reports published in languages other than English were excluded. Data were compiled into a detailed supplementary table and simple descriptive analysis was used to interpret data. A total of 22 cases were included, which constituted 14 individual case reports and two case series. The immunotherapy prescribed consisted of antibodies against and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) in all 22 patients. Out of them, immunotherapy consisting of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies was prescribed in nine patients. Fever was the most common symptom at the presentation (90.9%). The most common laboratory findings were anemia (90.9%), thrombocytopenia (90.9%), and elevated ferritin (90.9%). All the patients received steroids (100%). HLH responded to treatment in 19 patients. Three patients died. Three patients were rechallenged with immunotherapy, with no recurrence of HLH. HLH in the setting of ICI therapy is life-threatening, but potentially treatable with early detection. However, diagnosis is often delayed due to difficulty in differentiating the presenting symptoms and laboratory findings from complications of cancer and other therapies. Majority have shown an adequate response to standard HLH treatment; however, some required a longer course of corticosteroids. HLH is not always associated with other irAE. Rechallenging with immunotherapy was successful in some patients after completing treatment for HLH.

Dataset Information

Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study.

Background

Methods/results

Conclusion

Publications

Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: a retrospective cohort study.

Similar Datasets

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