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Oncology nurses frequently encounter infusion-related reactions when administering cancer therapies. Knowing how to recognize and intervene during these reactions is essential to patient safety and quality care. This article reviews potential signs and symptoms of infusion-related reactions, the pathophysiology behind these reactions, risk factors, and management strategies.

Aim: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. Method: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. Findings: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3–4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). Discussion: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC. © 2021 Taylor & Francis Group, LLC.

Background: A large proportion of patients with inflammatory bowel disease (IBD) relapse after drug discontinuation despite achieving a stable state of infliximab-induced clinical remission. Resuming the use of the same tumor necrosis factor-alpha (TNF-α) inhibitors in patients who relapse following TNF-α inhibitor discontinuation was suggested as a treatment strategy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of infliximab retreatment in patients with IBD. Methods: A systematic literature search to shortlist relevant studies was conducted using the MEDLINE, Embase, CINAHL, and SCOPUS databases for studies published from inception to August 2020. Results: Nine studies were included in the meta-analysis. The pooled clinical remission rate of infliximab retreatment in patients with IBD was 85% (95% confidence interval (CI), 81–89%) for induction treatment and 73% (95% CI, 66–80%) for maintenance treatment. A clinical remission rate following infliximab reintroduction was achieved in a greater proportion of patients with Crohn’s disease (87%; 95% CI, 83–91%) than in those with ulcerative colitis (78%; 95% CI, 61–91%) for induction treatment, but the difference was not statistically significant. Infusion-related reactions after infliximab retreatment occurred in 9% of patients with IBD (95% CI, 3–16%). Conclusion: Infliximab retreatment showed high clinical remission rates with tolerable infusion-related reactions in patients with IBD who achieved remission with initial infliximab treatment but relapsed after its discontinuation. We suggest infliximab as a viable alternative in patients with IBD who previously responded well to infliximab treatment.

Objective The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. Methods In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. Results Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (− 2.7 and − 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. Conclusion CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. ClinicalTrials.gov identifier NCT02149121. Electronic supplementary material The online version of this article (10.1007/s40259-018-00331-4) contains supplementary material, which is available to authorized users.

Purpose Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours. The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion. Patients and methods All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infusion protocol, 20% of the dose was administered over 30 minutes and the remaining 80% over 60 minutes. Results From April 1 to May 31, 2019, 25 patients received 53 90-minute infusions of daratumumab. Premedication included corticosteroids, antipyretics, antihistamines, and if necessary a leukotriene receptor antagonist. No grade 3 or grade 4 IRRs were observed. Conclusion From the third infusion, we found that a rapid administration of daratumumab (90 vs 210 minutes) was well tolerated and safe. It would be interesting to test this regimen from the second infusion.

Incidence of infusion related reaction (IR) is more common with cetuximab (Cmab) than with panitumumab (Pmab). Although little is known about rechallenge IR with monoclonal antibodies, we experienced a successful rechallenge to Cmab after IR to Pmab. A 67-year-old female patient was scheduled for chemotherapy with mFOLFOX6 plus Pmab against unresectable advanced rectal cancer in the hope of tumor shrinkage. On the first administration of Pmab, she complained of dyspnea with shortness of breath and wheezing, even after premedication with steroids and antihistamines. Her reaction was judged as Grade 2 IR to Pmab. For the next course, we tried Cmab. No IRs were observed. Since then, she has undergone seven further courses of treatment, followed by surgical resection. The patient benefited from administration of Cmab after experiencing IR to Pmab, suggesting this treatment to be an option for patients of this type who experience IR to Pmab.

WOS: 000411827200025, PubMed ID: 28961828, Background: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. Patients and methods: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Results: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Conclusions: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Background/Aims This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy. Methods The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor’s progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria. Results IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029). Conclusions Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.

Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates. To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent. We reviewed the rate of infusion-related reactions (IRRs) in the first 12 months of our single-institution experience using shortened infusion times for combined checkpoint inhibition with ipilimumab and nivolumab. Between May 24, 2016 and June 10, 2017, a total of 46 melanoma patients received 100 shortened cycles of combined 3 mg/kg ipilimumab and 1 mg/kg nivolumab. One patient (2.2%; 1/46) had a questionable reaction after administration of 1 mg/kg nivolumab over 30 min, but none of the other patients had a bona fide IRR. Shortened infusion times for combined ipilimumab and nivolumab treatment are safe, thereby facilitating a more efficient use of outpatient facilities and enhancing patient’s convenience.

Background Erythroderma, or red man's syndrome, is a common infusion-related reaction following vancomycin administration. Erythroderma following daptomycin rapid infusion has not been documented. Objective To report a case of erythroderma following daptomycin 2-minute intravenous (IV) injection. Case Report A review of published literature suggests that this is the first published case of a flushing (nonallergic) reaction resulting from a 2-minute IV injection of daptomycin that is not present with standard IV infusion. A 69-year-old woman following right knee reconstructive surgery presented with right knee joint swelling, purulent discharge, and fever. Subsequently, she was diagnosed with a presumed postsurgical infection and was initiated on vancomycin therapy. Following removal of the infected hardware, the patient was discharged and continued outpatient vancomycin therapy. The patient's renal function began to decline and therapy was discontinued. Daptomycin 6 mg/kg every 48 hours was initiated via 2-minute IV push. On the initial dose, approximately 2 hours post IV infusion, the patient began to notice redness and a warm sensation on her face, neck, and upper part of the chest. Diphenhydramine 25 mg provided limited immediate relief, but all symptoms subsided within 3 to 4 hours. The patient received her next dose 48 hours later over a 40-minute IV infusion with no adverse effects. Subsequent infusions continued at the same dose over 30 minutes for 4 weeks with no further adverse effects. Conclusion A 2-minute intravenous injection of daptomycin in this patient yielded a reaction that was not present on rechallenge with standard, extended infusion.

Background SB2 is developed as a biosimilar of the infliximab reference product (INF). The 30-week and 54-week results of Phase III study have been reported1,2. Objectives To evaluate the safety, immunogenicity, and efficacy in patients with RA who transitioned from INF to SB2 vs maintained INF and who continued to receive SB2 after Week 54 up to Week 78. Methods This study is a randomised, double-blind phase III transition study. Patients with moderate to severe RA were randomised in a 1:1 ratio to receive either SB2 or INF at Weeks 0, 2, 6, and then every 8 weeks thereafter until week 46. At Week 54, patients previously receiving INF were re-randomised in a 1:1 ratio to either receive SB2 (INF/SB2) or continue INF (INF/INF) up to week 70; patients receiving SB2 continued to receive SB2 (SB2/SB2) up to Week 70. Safety, immunogenicity and efficacy were assessed up to week 78. Results At Week 54, 94 patients from INF were transitioned to SB2 (INF/SB2), 101 patients from INF continued to receive INF (INF/INF), and 201 patients from SB2 continued to receive SB2 (SB2/SB2). The safety profile during the transition period was comparable between INF/SB2, INF/INF, and SB2/SB2. The incidence of adverse events during the transition period was 36.2% in INF/SB2, 35.6% in INF/INF, and 40.3% in SB2/SB2. The incidence of infusion related reaction during the transition period was 3.2%, 2.0%, and 3.5%, respectively. Among the patients with overall negative anti-drug antibodies (ADA) results up to Week 54, ADAs were newly developed in 14.6% (6/41) in INF/SB2, 14.9% (7/47) in INF/INF, and 14.1% (11/78) in SB2/SB2. The efficacy was sustained and comparable between the treatment groups. Conclusions The safety, immunogenicity, and efficacy profiles remained comparable between the INF/SB2, INF/INF, and SB2/SB2 up to Week 78, revealing that there were no treatment emergent issues or clinically relevant immunogenicity after switching from INF to SB2. References Choe JY et al. Ann Rheum Dis. 2015–207764 [Epub ahead of print] Choe JY et al. Arthritis Rheumatol. 2015; 67 (suppl 10), 2056 Disclosure of Interest J. S. Smolen Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glazo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB, J.-Y. Choe Grant/research support from: Samsung Bioepis, Consultant for: Samsung Bioepis, N. Prodanovic Grant/research support from: Samsung Bioepis, J. Niebrzydowski Grant/research support from: Samsung Bioepis, I. Staykov Grant/research support from: Samsung Bioepis, E. Dokoupilova Grant/research support from: Samsung Bioepis, A. Baranauskaite Grant/research support from: AbbVie, Samsung Bioepis, R. Yatsyshyn Grant/research support from: Samsung Bioepis, M. Mekic Grant/research support from: Samsung Bioepis, W. Porawska Grant/research support from: Samsung Bioepis, H. Ciferska Grant/research support from: Samsung Bioepis, K. Jedrychowicz-Rosiak Grant/research support from: Samsung Bioepis, A. Zielinska Grant/research support from: Samsung Bioepis, J. Choi Employee of: Samsung Bioepis, Y. H. Rho Employee of: Samsung Bioepis

Aim To describe a case of severe infusion-related reaction to liposomal amphotericin B (LAB). Clinical details A severely immunocompromised 58-year-old male with acute myeloid leukaemia experienced 2 infusion-related adverse events when treated with LAB for a localised Fusarium solani fungal infection of the right forefoot. The initial adverse reaction to LAB was not serious. However, the second adverse reaction following a re-challenge was serious. The patient had a poor prognosis because of the likelihood of further chemotherapy-induced neutropenia and a potentially untreated disseminated fungal infection in light of planned chemotherapy. Outcomes LAB was successfully substituted with conventional amphotericin B to treat Fusarium solani infection. No adverse events were observed with conventional amphotericin B. Conclusion The patient is suspected to have had a reaction to the lipid carrier of LAB.

Background From 2009 Abatacept (ABA) – a new generation biological DMARD was approved in Russia. ABA selectively modulates T-cell activation, which seems to play the key role in the pathogenesys of JIA. Efficacy and safety of ABA was assessed in AWAIKEN trial in different types of patients who had polyarticular course of JIA at the enrollment. This prospective observation was aimed to assess effectiveness and safety of ABA in patients with different types and clinical variants of active JIA in real clinical practice. Methods 27 children with JIA were treated with ABA. 20 (74%) pts had polyarticular course of JIA and 7 (26%) - systemic JIA. 25 (93%) of pts were female. All patients had high degree (III) of disease activity. Mean disease duration was 5,9 ± 3,3yr. 26 patients previously had an inadequate response to 2 or more non-biological, one child with heavy course of systemic JIA was treated with infliximab during 1 year before starting ABA. Treatment effectiveness was assessed according to the ACR Pediatric criteria: ACR pedi 30, ACR pedi 50, ACRpedi 70, and ACR pedi 90 after 6 and 12 months of abatacept therapy. All patients received ABA in dose 10 mg/kg at day 1, week 2 and 4 and every 4 weeks thereafter. Results In the group of pts with systemic JIA after 6 months of ABA treatment 6 of 7 patients (86%) achieved ACR Pedi 30 response, 5 (71%) – ACR Pedi 50, and 3 (43%) – ACR Pedi 70. 12 months data was available for 5 patients (others are still on treatment but less than 12 moths). Four of five pts (80%) achieved ACR pedi-30, 3(60%) - ACR Pedi 50 response, 2 (40%) ACR pedi 70, and 1 (20%) ACR pedi 90. In the group of pts with poliarticular course of JIA treatment effectiveness was assessed in 19 pts. One girl had experienced an infusion-related reaction (potentially associated with hypersensitivity) after 3rd infusion and ABA treatment was stopped. After 6 months 17 of 19 pts (89%) achieved ACR pedi 30 response, 14 (74%) - ACR pedi-50, 6 (32%) - ACR pedi-70, 2 (11%) - ACR pedi 90. 11 of 20 patients with polyarticular JIA have completed 12 months of ABA treatment. 9 of them (82%) achieved ACR pedi 30 response, 8 (73%) - ACR pedi 50, 5 (45,0%) - ACR pedi 70 and 1 (9%) - ACR pedi 90. Adverse events were observed in 2 patients (7,4%): 1 case of infusion related reaction, 1 pts experienced common Herpes simplex infection (ABA treatment was stopped after 12 months). Conclusions Abatacept have shown its effectiveness in the majority of patients with long standing JIA (systemic and polyarticular course) with high disease activity, and inadequate response to previous treatment with DMARDs. Better results were observed in patients with poliarticular JIA. Disclosure of Interest None Declared