Autoimmune haemolytic anaemia in a patient with advanced lung adenocarcinoma and chronic lymphocytic leukaemia receiving nivolumab and intravenous immunoglobulin

Algaze, Sandra; Park, Wungki; Harrington, Thomas J.; Mudad, Raja

doi:10.1136/bcr-2017-221801

Cited by 13 publications

(10 citation statements)

References 30 publications

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“…We identified 17 published cases of ICPi‐AIHA . The clinical and laboratory features of ICPi‐AIHA in these 17 cases are summarized in Supporting Information Table S3.…”

Section: Resultsmentioning

confidence: 99%

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors

et al. 2019

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Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi-AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22-110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2-12.9 g/dL) and 6.3 g/dL (IQR, 6.1-8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi-AIHA were similar in DAT positive and negative patients. ICPi-AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi-AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first-line treatment in the majority of patients with ICPi-AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA. a Long-standing history of leukopenia of unclear etiology, bone marrow biopsy negative for malignancy, and leukopenia believed to be autoimmune in nature. b Received indoximod in combination with ICPi therapy as part of a clinical trial. c R-CHOP, fludarabine (received >3 years prior to development of AIHA), XRT, auto-SCT for treatment of MZL, and cisplatin and etoposide for treatment of NSCLC. d Received nivolumab on a clinical trial after conventional chemotherapy. e 5-FU, oxaliplatin, irinotecan, bevacizumab, panitumumab, regorafenib, and trifluridine/tipiracil. f Received GVAX and cyclophosphamide in combination with ICPi therapy as part of a clinical trial. g Dabrafenib, trametinib for treatment of melanoma, fludarabine (received >3 years prior to development of AIHA), cyclophosphamide, bendamustine, rituximab, obinutuzumab, and ibrutinib for treatment of CLL.

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“…We identified 17 published cases of ICPi‐AIHA . The clinical and laboratory features of ICPi‐AIHA in these 17 cases are summarized in Supporting Information Table S3.…”

Section: Resultsmentioning

confidence: 99%

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors

et al. 2019

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“…Autoimmune hemolytic anemia (AIHA) occurs at a variable frequency, and it seems to be slightly more common with PD-1/PD-L1 inhibitors [ 62 ] The median time to onset is about 50 days, and mortality is nearly 15%. Some reports point to an association between ICI-induced AHAI and chronic lymphocytic leukemia, sugges-ting a potential increased risk of hematological immune toxicity in these patients [ 64 ]. Delanoy et al published a cohort of 35 cases (3 with chronic lymphocytic leukemia) and suggested to rule out the presence of an underlying chronic lymphocytic leukemia in any patient with a suspected immune-related hematological toxicity.…”

Section: Methodsmentioning

confidence: 99%

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

et al. 2022

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Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages. Here, we comprehensively review some uncommon, but exceedingly important, immune-related adverse events, with special emphasis in the clinical approach and diagnostic workup, aiming to reunite the evidence published previously, allowing an increase in awareness and knowledge from all specialists implicated in the diagnosis, treatment, and care of cancer patients treated with immunotherapy.

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“…Besides durable and impressive clinical effects, ICIs could also induce multiple severe or even fatal organ system toxicities, including those of the hematological system. Frequently reported clinical hematological complications include neutropenia, 8 immune thrombocytopenia, 9 autoimmune hemolytic anemia, 10 and immune thrombocytopenic purpura 11,12 . ICI‐induced hematological AEs are rare but potentially life‐threatening events 10‐12 .…”

Section: Introductionmentioning

confidence: 99%

“…Frequently reported clinical hematological complications include neutropenia, 8 immune thrombocytopenia, 9 autoimmune hemolytic anemia, 10 and immune thrombocytopenic purpura 11,12 . ICI‐induced hematological AEs are rare but potentially life‐threatening events 10‐12 . However, these toxicities are sparsely reported in the related literature and their frequency, spectrum, and outcomes are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019

Zhai

et al. 2020

Hematological Oncology

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Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC 025) exceeding zero or that of ROR (ROR 025) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC 025 : 0.81; ROR 025 : 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR 025 : 1.04) and anti-CTLA-4 monotherapy groups (anti-CTLA-4 vs anti-PD-1, ROR 025 : 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR 025 : 1.11). Moreover, class-specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI-associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti-CTLA-4 therapy) and reinforced by polytherapy. A spectrum of class-specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non-negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICIrelated hematological AEs are highly important and further studies are needed to confirm the results of our study.

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Autoimmune haemolytic anaemia in a patient with advanced lung adenocarcinoma and chronic lymphocytic leukaemia receiving nivolumab and intravenous immunoglobulin

Cited by 13 publications

References 30 publications

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019

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