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Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout.

ABSTRACT: To assess frequency and distribution of infusion reactions (IRs) in responders and nonresponders in randomized clinical trials (RCTs) of intravenous pegloticase and the utility of the National Institute of Allergy and Infectious Disease/Food and Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for identifying anaphylaxis in subjects experiencing IRs.IRs from two RCTs of pegloticase were evaluated and categorized as anaphylaxis, hypersensitivity, or other. Serum levels of tryptase and total hemolytic complement (CH50) were evaluated at the time of all IRs. Frequency of IRs by each category was evaluated in all subjects, responders or nonresponders to pegloticase.There were 113 IRs in 1695 infusions. Of the 113 IRs, 6 met criteria for anaphylaxis, 53 had one feature of anaphylaxis and were designated as "hypersensitivity", and 54 had no features and were designated "other". In subjects receiving pegloticase every 2 weeks (Q2w), a total of 852 infusions were administered and the IR frequency was 0.5% in responders and 9.7% in nonresponders. In subjects receiving pegloticase every 4 weeks (Q4w), a total of 846 infusions were given and the IR frequency was 2.6% in responders and 12.2% in nonresponders. There were no differences among the three categories of IRs with regard to clinical course or biochemical evidence of immune activation determined by CH50 or tryptase levels.IRs mostly occurred in nonresponders. NIAID/FAAN criteria for anaphylaxis did not identify pegloticase-related IRs as having a higher frequency of immune activation or a more severe course. The results are consistent with the conclusion that discontinuance of pegloticase if uric acid rises to >6 mg/dL will decrease the frequency of IRs.

SUBMITTER: Calabrese LH

PROVIDER: S-EPMC5561590 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Background aimsThe use of natural killer (NK) cells as a cellular immunotherapy has increased over the past decade, specifically in patients with hematologic malignancies. NK cells have been used at the authors' institution for over 15 years. Most patients have a reaction to NK cell infusion. The authors retrospectively analyzed the reactions associated with NK cell infusions to characterize the types of reactions and investigate why some patients have higher-grade reactions than others.MethodsA retrospective chart review of NK cell infusions was performed at the authors' institution under nine clinical protocols from 2008 to 2016. An infusion reaction was defined as any symptom from the time of NK cell infusion up to 4 h after infusion completion. The severity of infusion reactions was graded based on Common Terminology Criteria for Adverse Events, version 4. Two major endpoints of interest were (i) infusion reaction with any symptom and (ii) grade ≥3 infusion reaction. Multivariable logistic regression models were used to investigate the association between variables of interest and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained for each variable.ResultsA total of 130 patients were receiving NK cell infusions at the authors' institution. The most common reported symptom was chills (n = 110, 85%), which were mostly grade 1 and 2, with only half of patients requiring intervention. There were 118 (91%) patients with infusion reactions, and only 36 (28%) were grade 3. There was one life-threatening grade 4 reaction, and no death was reported due to infusion reaction. Among grade ≥3 reactions, cardiovascular reactions (mainly hypertension) were the most common, and less than half of those with hypertension required intervention. NK cell dose was not associated with any of the grade 3 infusion reactions, whereas monocyte dose was associated with headache (grade ≤3, OR, 2.17, 95% CI, 1.19-3.97) and cardiovascular reaction (grade ≥3, OR, 2.13, 95% CI, 1.13-3.99). Cardiovascular reaction (grade ≥3) was also associated with in vitro IL-2 incubation and storage time. Additionally, there was no association between grade ≥3 infusion reactions and overall response rate (OR, 0.75, 95% CI, 0.29-1.95).ConclusionsThe majority of patients who receive NK cell therapy experience grade 1 or 2 infusion reactions. Some patients experience grade 3 reactions, which are mainly cardiovascular, suggesting that close monitoring within the first 4 h is beneficial. The association of monocytes with NK cell infusion reaction relates to toxicities seen in adoptive T-cell therapy and needs further exploration.

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Frequency, distribution and immunologic nature of infusion reactions in subjects receiving pegloticase for chronic refractory gout.

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