Incidence Of Infusion-related Reactions Research Articles

Infusion reactions are common after high-dose carmustine in BEAM chemotherapy and are not reduced by lengthening the time of administration.

Carmustine (BCNU) is used in the conditioning regimens BEAM and CBV for autologous stem cell transplantation. Carmustine-related infusion reactions, while not described in the BEAM literature, occurred in 95% of patients who received CBV. The most common symptoms include flushing, facial pain, headache, and hypotension. These reactions have been attributed to the absolute ethanol that is used in the reconstitution process or alternatively by a direct effect of carmustine. It is currently recommended that carmustine 300mg/m2 be infused over at least 100min (3-5mg/m2/min). Prior to October 2014, carmustine infusions were given over 90min but were changed to 120min based on the above recommendation. We compared the two infusion rates in patients receiving BEAM to see if lengthening the infusion decreased the frequency of reactions. Overall, 100 patients received BCNU as part of BEAM or Zevalin BEAM and were equally divided between 90 and 120min infusion times. The primary outcome was the incidence of infusion-related reactions which were graded based on CTCAE 4.03 descriptions of flushing and infusion-related reactions. We also evaluated the impact of premedication as well as the efficacy of medications used to treat infusion reactions. Between the years 2013-2016, there were 50 patients who received BCNU over 90min and 50 patients over 120min. There were no significant differences observed for diagnosis, age and gender between the two groups. Twenty-eight (56%) in the 90-min and 26 (52%) in the 120-min infusion intervals developed a reaction (p = 0.6882). Of the patients that developed a reaction, 19 patients (67%) in the 90-min and all 26 patients (100%) in the 120-min infusion were given premedications predominately acetaminophen, in addition to dexamethasone. Among reacting patients, 57% of the 90-min and 65% of the 120-min groups received additional intervention (p = 0.53). Infusion reactions during high-dose BCNU are common and are not clearly reduced by modestly extending the duration of infusion or giving premedications.

Analysis of clinical trials of biosimilar infliximab (CT-P13) and comparison against historical clinical studies with the infliximab reference medicinal product

Objective: To examine whether efficacy, safety and pharmacokinetic (PK) data observed with CT-P13 (Remsima®; Inflectra®), an infliximab biosimilar, are similar to those from published reports with the reference medicinal product (RMP; Remicade®) in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Methods: Literature searches were performed to identify clinical studies with infliximab RMP. Efficacy, safety and PK data were indirectly compared with data from head-to-head clinical trials of CT-P13 and RMP. Results: CT-P13 and RMP produce similar efficacy in patients with RA and AS when compared across clinical studies. There are no substantial differences in the incidence of infusion-related reactions, infections, serious infections, malignancy or lymphoma. PK data in patients with RA are similar in direct comparisons and comparisons with historical data. Conclusion: Efficacy, safety and PK data are highly comparable between CT-P13 and RMP, both in head-to-head clinical studies, and indirect comparisons with historical clinical data for RMP.

Safety of infusing rituximab at a more rapid rate in patients with rheumatoid arthritis: results from the RATE-RA study.

BackgroundAs recommended in the current prescribing information, rituximab infusions in patients with rheumatoid arthritis (RA) take 4.25 hours for the first infusion and 3.25 hours for subsequent infusions, which is a burden on patients and the health care system. We therefore evaluated the safety of infusing rituximab at a faster rate for an infusion period of 2 hours in patients with RA.MethodsPatients with an inadequate response to anti-TNF who were rituximab-naive or -experienced received 2 courses of rituximab: Infusion 1 (Day 1) was administered over the standard 4.25 hours, and Infusions 2 (Day 15), 3 (Day 168) and 4 (Day 182) were administered over a faster 2-hour period. The primary endpoint was incidence of infusion-related reactions (IRRs) associated with Infusion 2.ResultsOf the 351 patients enrolled, 87% and 13% were rituximab-naive and -experienced, respectively. The incidence (95% CI) of IRRs associated with Infusion 1 was 16.2% (12.5%, 20.5%) and consistent with weighted historical incidence of 20.7% (19.4%, 22.1%). The incidence (95% CI) of IRRs associated with Infusions 2, 3, and 4 compared with respective weighted historical incidences at the standard infusion rate was 6.5% (4.1%, 9.7%) vs 8.1% (7.2%, 9.1%); 5.9% (3.5%, 9.3%) vs 11.5% (10.3%, 12.8%); and 0.7 (0.1%, 2.6%) vs 5.0% (4.2%, 6.0%), respectively. All IRRs were grade 1 or 2, except for 3 grade 3 IRRs associated with Infusion 1 and 2 grade 3 IRRs associated with Infusion 2. Four patients experienced a total of 5 grade 3 IRRs; 3 of these patients continued on to received subsequent infusions at the faster rate. There were no serious IRRs.ConclusionThis study demonstrated that rituximab can be administered at the faster infusion rate at the second and subsequent infusions without increasing the rate or severity of IRRs.

The Incidence and Risk Factors of Infusion-Related Reactions to Rituximab for Treating B Cell Malignancies in a Single Tertiary Hospital

Background: Rituximab is a chimeric anti-CD20 human/mouse monoclonal antibody. As its usage has increased, there have been growing concerns about rituximab-related infusion-related reactions (IRRs). Objective: The aim of this study is to verify the clinical features and risk factors of IRRs by rituximab, and to help establish clinical guidelines for their prevention. Methods: We reviewed electronic medical records of all the adult patients who were prescribed rituximab from January 2005 to July 2010 for B cell malignancy at Seoul National University Hospital. Results: A total of 389 cases of IRRs by rituximab (12.5% of a total of 3,104 infusions) were identified in 281 patients (49.4% of a total of 568 patients). IRRs most frequently occurred during the first infusion (40.5%) and abruptly decreased in subsequent infusions to rates of 3-8% (p < 0.001). The incidence of IRRs in patients premedicated with corticosteroid for their first infusion was significantly lower when compared to patients not pretreated with corticosteroid prior to rituximab infusion (8.3 vs. 41.2%, p = 0.017). Conclusion: Almost half of all patients in the study experienced IRRs at least once during their scheduled rituximab treatment. Premedication with corticosteroid can be recommended in patients with high risk of IRR in the first infusion.

AB0302 Results from the rate-ra study: a multicenter, open-label, single-arm study to evaluate the safety of administering rituximab at a more rapid infusion rate in patients with rheumatoid arthritis

BackgroundThe labelled dose of rituximab (RTX) in rheumatoid arthritis (RA) is 2 × 1000 mg IV infusions given 2 weeks apart (1 course), with recommended times of 4.25 hours (h)...

A nurse-led accelerated infliximab infusion service: patient satisfaction and safety

Many inflammatory bowel disease (IBD) nurse specialists now have the responsibility of managing a biologics service, and with more referrals come issues of bed capacity and patient satisfaction. While accelerated infusions—where infliximab is given according to a structured protocol over a shorter period—have been shown to be safe in rheumatology patients, there are limited data looking specifically at IBD patients. In this paper, Kay Greveson and Sue Woodward describe a prospective service development review that was conducted to determine the incidence of infusion-related reactions with an accelerated-infusion protocol and to explore patient perceptions of a nurse-led accelerated-infusion regimen.

Optimizing Premedications in the Prevention of Bendamustine Infusion-Related Reactions

Bendamustine is indicated for the treatment of chronic lymphocytic leukemia (CLL) and rituximab refractory indolent non-Hodgkin lymphoma. Clinical trials have reported a 25% incidence of infusion-related reactions (IRRs) in patients receiving bendamustine. While these reactions are well documented, there is no consensus on the optimal premedication regimen for the prevention of these adverse effects. At our center, we utilize a regimen of ondansetron 16 mg orally and dexamethasone 10 mg IV push prior to each infusion of bendamustine. This report describes our experience with our current premedication regimen with regard to IRRs and the incidence of febrile neutropenia (FN). We retrospectively analyzed 73 consecutive patients receiving bendamustine infusions at our institute from June 2008 to June 2010 to determine the incidence of IRRs and FN. The primary objective was to determine the incidence of IRRs. Secondary objectives included incidence of FN and hospital admission rate. A total of 478 infusions of bendamustine were administered to 73 consecutive patients. The median patient age was 69 years. IRRs affected 19% of our population, and 10.9% experienced FN. Notably, all IRRs were attributed to rituximab infusions and no patients experienced an IRR when receiving bendamustine alone. This compares favorably to the initial reported IRRs of 25% with bendamustine alone. Based on our experience with bendamustine, ondansetron and dexamethasone provide a safe and effective prevention of IRRs associated with bendamustine. By avoiding the use of other premedications, the likelihood of additional complications or adverse affects can be minimized.

Optimizing Premedications In the Prevention of Bendamustine Infusion Related Reactions

AbstractAbstract 4370 IntroductionBendamustine is indicated for the treatment of CLL and rituximab-refractory indolent NHL. Clinical trials have reported 25% incidence of infusion related reactions (IRR) in patients receiving bendamustine. While these reactions are well documented, there is no consensus on the optimal premedication regimen for the prevention of these adverse effects. The Moffitt Cancer Center (MCC) utilizes a regimen of ondansetron 16 mg PO and dexamethasone 10 mg IVP prior to each bendamustine infusion. Herein, we report our experience with our current premedication regimen with regards to the IRR as well as the incidence of febrile neutropenia (FN). MethodsWe retrospectively analyzed 79 consecutive patients receiving bendamustine infusions at MCC from June 2008 to June 2010 to determine the incidence of IRR and FN. Data collected include baseline laboratory values, diagnosis, dosing, number of bendamustine infusions, concurrent rituximab use, growth factor utilization, as well as safety data including the rate of adverse reactions, interventions, and hospitalization. The primary objective was to determine the incidence of IRR. Secondary objectives include incidence of febrile neutropenia and hospital admission rate. All analyses were performed using SPSS 17.0. Descriptive statistics were used to analyze data. Results79 consecutive patients received a total of 513 bendamustine infusions at MCC. Median age was 68 years; M:F (52:27). The most common primary malignancies were indolent non-Hodgkin's lymphoma (NHL), 56%; chronic lymphocytic leukemia (CLL), 38%; and multiple myeloma (MM) 6.3%. Patients had received a median of 2 regimens prior to initiation of bendamustine. Bendamustine was utilized as first line treatment in 25% of patients, second line in 17.7%, third line in 25%, and fourth line or greater in 32.3% of patients. Bendamustine infusions were well-tolerated. Infusion-related reactions (IRR) occurred at a rate of 3.35% (17/513) with all reactions attributed to rituximab. Most commonly reported reactions reported were rigors (2%), chills (1%), and fever (<1%). IRR did not occur in patients receiving bendamustine alone. Overall incidence of FN was 11% (9/79). Of 9 patients that developed FN, 7 patients received bendamustine as 3rd line treatment or greater. The incidence of FN in patients that received bendamustine as 1st or 2nd line treatment was 6% (2/36). Patients that received bendamustine as 3rd line or greater had a 16% (7/43) incidence of FN. ConclusionBased on our experience with bendamustine, ondansetron and dexamethasone provide safe and effective prevention of infusion related reactions associated with bendamustine. Notably, all infusion reactions were attributed to rituximab infusions and no patients experienced an infusion related reaction when receiving bendamustine alone. This compares favorably to the initial reported infusion-related reactions with bendamustine alone (25%). In avoiding the use of other premedications, the likelihood of additional complications or adverse affects can be minimized. The overall incidence of FN was comparable to previously published studies. As may be expected, heavily pretreated patients had a higher incidence of FN (6% vs. 16%) than those who had received 1 or no previous treatments and may warrant growth factor support. Disclosures:Tombleson:Cephalon: Research Funding. Off Label Use: Bendamustine used for the treatment of myeloma. Ho:Cephalon: Consultancy, Research Funding. Pinilla-Ibarz:Cephalon: Speakers Bureau. Wetzstein:Cephalon: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Comparison of 2 Doses of Liposomal Amphotericin B and Conventional Amphotericin B Deoxycholate for Treatment of AIDS‐Associated Acute Cryptococcal Meningitis: A Randomized, Double‐Blind Clinical Trial of Efficacy and Safety

BACKGROUND. It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis. However, administration of this drug is accompanied by substantial adverse effects. This double-blind study, performed before the routine availability of highly active antiretroviral therapy, was designed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome (AIDS) and acute cryptococcal meningitis. METHODS. Patients were randomized (ratio, 1:1:1) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day (n = 87), liposomal amphotericin B at 3 mg/kg/day (n = 86), or liposomal amphotericin B at 6 mg/kg/day (n = 94). RESULTS. Efficacy was similar among all 3 treatment groups. The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B, compared with conventional amphotericin B (P < .001). Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity, indicated by a doubling of the serum creatinine value, compared with recipients of conventional amphotericin B (P = .004). Overall mortality at 10 weeks was 11.6%, with no significant differences among the treatment groups. CONCLUSIONS. Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis. Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects.

Premedication and incidence of infusion-related reactions in patients with metastatic colorectal cancer treated with cetuximab plus irinotecan-based chemotherapy.

3561 Background: The randomized phase III CRYSTAL study (n=1,202) and the large phase II MABEL study (n=1,147) confirmed the benefit of adding cetuximab respectively to infusional 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) or irinotecan alone in the first- or subsequent-line treatment of patients (pts) with metastatic colorectal cancer (mCRC). Methods: A post hoc analysis of the pooled population of pts receiving cetuximab was performed to investigate the effect of adding corticosteroid to antihistamine prophylactic premedication on the incidence of infusion-related reactions (IRRs) occurring following the first cetuximab infusion. Results: The incidence of grade 3/4 IRRs based on a broad selection of medical conditions (preferred Medical Dictionary for Regulatory Activities terms) was 1.0% in pts who received antihistamine plus corticosteroid as prophylactic premedication compared with 2.7% in those who received antihistamine alone. A comparable trend was seen for any grade IRRs (8.3% vs. 21.0%, respectively). In pts with a known or suspected or without predisposition to allergic reactions, a lower incidence of grade 3/4 and any grade IRRs occurred in each case for pts receiving antihistamine plus corticosteroid compared with antihistamine alone. Conclusions: These retrospective results indicate that the incidence of cetuximab-related grade 3/4 IRRs was reduced to 1.0% by a combined prophylaxis consisting of an antihistamine and a corticosteroid. N IRR incidence, N (%) Grade 3/4 Grade 4 Any grade Pooled population 1,747 Prophylactic pretreatment Antihistamine alone 596 125 (21.0) 16 (2.7) 7 (1.2) Antihistamine plus corticosteroid 1,061 88 (8.3) 11 (1.0) 2 (0.2) Other 90 Patients without predisposition to allergies 1,507 Prophylactic pretreatment Antihistamine alone 531 106 (20.0) 13 (2.4) 6 (1.1) Antihistamine plus corticosteroid 899 70 (7.8) 8 (0.9) 2 (0.2) Other 77 Patients with known or suspected* predisposition to allergies 240 Prophylactic pretreatment Antihistamine alone 65 19 (29.2) 3 (4.6) 1 (1.5) Antihistamine plus corticosteroid 162 18 (11.1) 3 (1.9) 0 Other 13 * For example, asthma, dermatitis (if not clearly of allergic origin). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA, Merck Serono Amgen, AstraZeneca, Celgene, Fresenius Biotech, Merck Serono, Roche Amgen, Bristol-Myers Squibb, Merck Serono, Pfizer, Roche, sanofi-aventis Merck Serono

Reduced incidence of infusion‐related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication

: The multinational MABEL study of 1147 patients with metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen confirmed in a community practice setting the efficacy and safety of cetuximab combined with irinotecan. : This report describes a post hoc analysis of the influence of prophylactic premedication on the incidence of infusion-related reactions (IRRs) in the MABEL study. The analysis was focused on the subpopulation of patients premedicated with antihistamines either with (n = 700) or without (n = 422) corticosteroids. Stepwise Cox regression modeling was used to examine the explanatory value of the type of premedication on progression-free survival (PFS) and overall survival (OS) times. : The incidence of IRRs was lower in the group of patients who received antihistamine plus corticosteroid (9.6%) compared with those who received antihistamine alone (25.6%). A similar trend was seen for grade 3 or 4 IRRs (1.0% vs 4.7%, respectively). The 12-week PFS rates (61% vs 60%), median PFS (16.1 vs 13.1 weeks) and OS (9.2 vs 9.0 months) times for patients who received, respectively, antihistamines with and without corticosteroids were similar. Cox regression modeling did not identify any impact of type of premedication used (antihistamine with or without corticosteroids) on the efficacy of treatment in relation to PFS or OS. : Prophylactically premedicating mCRC patients with both antihistamine and a corticosteroid appeared to reduce the frequency of cetuximab-associated IRRs. Given that this was a post hoc analysis, caution must be exercised in the interpretation of these data, which require formal confirmation in a randomized study. Cancer 2010. (c) 2010 American Cancer Society.

Liposomal Amphotericin B

Liposomal Amphotericin B

Premedication Practices and Incidence of Infusion-related Reactions in Patients Receiving AMPHOTEC: Data from the PRoACT-Patient Registry of Amphotericin B Cholesteryl Sulfate Complex for Injection Clinical Tolerability

Premedication Practices and Incidence of Infusion-related Reactions in Patients Receiving AMPHOTEC: Data from the PRoACT-Patient Registry of Amphotericin B Cholesteryl Sulfate Complex for Injection Clinical Tolerability

Pre-medication practices and incidence of infusion-related reactions in patients receiving AMPHOTEC®: data from the Patient Registry of Amphotericin B Cholesteryl Sulfate Complex for Injection Clinical Tolerability (PRoACT) registry

Clinical studies have suggested that rates of infusion-related reactions (IRRs) may be higher with amphotericin B colloidal dispersion (ABCD) versus other forms of amphotericin B. However, these studies did not permit the use of pre-medications upfront, which are now commonly used. Objectives To describe the use of pre-medications and determine the rate of IRRs in the real-world setting. PRoACT, a multicentre, worldwide observational registry, captured real-world data about pre-medication practices and IRRs in patients receiving ABCD. Eligible patients were those beginning treatment with ABCD; treatment was according to the site's standard treatment practice. Incidence of IRRs was collected during the first 10 days of ABCD therapy. Clinical response data were collected 12 weeks after treatment start. One hundred and seventy patients from 21 worldwide sites were included (median age 37 years; 52% male). There were a total of 1230 ABCD infusions (mean dose 2.8 mg/kg/day); 90% of the infusions (1105/1230) had pre-medication. Common pre-medications included corticosteroids, antihistamines, paracetamol (acetaminophen) and metamizole. The overall IRR rate was 12% (147/1230) and was lower in infusions with pre-medication (11%) versus no pre-medication (22%), P < 0.001. Corticosteroids were associated with a decreased incidence of IRRs (P < 0.05), while paracetamol and antihistamines were not. The most common IRRs were chills (7%), fever (7%) and rigors (5%). Clearance of the fungal infection occurred in 52% of the participants. These data suggest a lower rate of IRRs with ABCD than previously reported. Pre-medication is associated with decreased IRR incidence. Corticosteroids in particular appear to decrease IRRs while paracetamol and antihistamines, though commonly used, do not.

411: Rituximab Monitoring in Hematopoietic Stem Cell Transplant: How much is Necessary?

Background: Rituximab, an uncongugated monoclonal antibody that reacts with the CD20 molecule present on most malignant B-cells, is standard treatment for patients with lymphoma. Most rituximab infusions are well tolerated with a mild infusion related symptom complex (fever, chills/rigors) usually occurring within 1 hour after initiation. Severe infusion related reactions (IRR), such as bronchospasm and hypotension, occur infrequently; most often within 2 hours after initiating the first dose. Reactions are caused by cytokine release associated with high numbers of circulating tumor cells. Incidence of IRRs decreases markedly with subsequent infusions. At a university based comprehensive cancer center, controlled trials using rituximab for treatment of NHL are underway in hematopoietic stem cell transplant patients to determine optimal dosing and scheduling. Patients participating in these trials are heavily pretreated with rituximab, and are in partial or complete remission before admission for transplant. Based on phase I and II trials, frequent vital sign (VS) monitoring and concurrent administration of normal saline are recommended. Current organizational clinical practice standards require between 10–16 sets of VS over 5–6 hours for average rituximab infusions; interfering with patient comfort and requiring significant nursing time. Purpose: To determine the frequency and risk of IRRs in patients admitted for transplant and an optimal vital sign monitoring schedule. Method: A nurse initiated, IRB-approved, retrospective review of 200 medical records was conducted. Data analysis is in progress to determine IRR frequency, identify patients at high risk for reactions, and determine an appropriate VS schedule. Results: Study findings will be reported.

Clinical effectiveness of trastuzumab: early experience

Objective. To assess the clinical effectiveness of trastuzumab among metastatic breast cancer (MBC) patients and compare the results to those reported in the two pivotal clinical trials and product monograph. Design. Retrospective chart review of all patients who had initiated trastuzumab monotherapy or combination therapy for MBC within the Alberta Cancer Board (ACB) from August 1998 to May 2001. Setting. Two public tertiary cancer centres in the Canadian province of Alberta. Patients. Of 90 patients reviewed within the ACB, 72 women were eligible for the study. Main outcome measures. The primary endpoints measured were time to treatment failure (TTF) and survival. Secondary end-points measured included adverse events and compliance with ACB guidelines for trastuzumab administration. Results. Among all 72 patients, median TTF was 7.6 months and median survival was 14.4 months. Trastuzumab combination therapy was associated with a significantly longer median TTF compared to trastuzumab monotherapy (P= 0.011). With respect to survival, no significant advantage was seen with combination therapy over monotherapy (P= 0.438). Infusion-related reactions were reported in 11.1% of our patients, while cardiotoxicity was reported in12.5%. Conclusions. Overall, we found that trastuzumab performs better in the clinical setting than it did in the pivotal trials with respect to TTF (2.5 vs. 2.4 months and 8.2 vs. 6.9 months), but not as well with respect to survival (10.0 vs. 13.0 months and 21.0 vs. 25.1 months). In comparison to the product monograph, we report a significantly lower incidence of infusion-related reactions and a slightly higher incidence of cardiotoxicity.