rituximab ( rituxan ) is a chimeric igg1 monoclonal antibody that targets the cd20 receptor and is used in the management of lymphoproliferative disorders .
rituximab is fda approved in the treatment of chronic lymphocytic leukemia ( cll ) , non - hodgkin 's lymphoma ( nhl ) , and rheumatoid arthritis ( ra ) .
rituximab is generally well tolerated ; however , there are risks associated with infusion - related toxicity including hypersensitivity reactions such as fever , urticaria , hypotension , and cardiovascular and respiratory compromise . the mechanism by which rituximab causes an infusion - related reaction is unclear but is thought to be due to the release of inflammatory cytokines .
the likelihood of infusion - related reactions is the highest with the first infusion and decreases with subsequent infusions with time to onset ranging from 30 to 120 minutes .
other risk factors for developing an infusion - related reaction include large tumor burden , pulmonary infiltrates , elderly patients , and individuals diagnosed with chronic lymphocytic leukemia or mantle cell lymphoma .
infusion related reactions typically resolve with supportive care and/or a decrease in the infusion rate .
the overall incidence of infusion - related reactions varies based on diagnosis but ranges from 32 to 77% with the first infusion of rituximab .
the incidence of grade 3 or 4 infusion - related reactions is reported to be 9% for the first infusion of rituximab with cyclophosphamide , doxorubicin , vincristine , and prednisone ( chop ) or cyclophosphamide , vincristine , and prednisone ( cvp ) chemotherapy regimens . in an effort to prevent infusion - related reactions
, the manufacturer recommends that the first infusion of rituximab be given at a slow initial rate and gradually titrated upward which may take up to 6 to 8 hours .
specifically the initial rituximab infusion should be started at a rate of 50  mg / hr , and if tolerated further titrate the rate by 50  mg / hr every 30 minutes to a maximum rate of 400  mg / hr . for subsequent infusions , the starting rate should be 100  mg / hr , and if tolerated , the rate can be further increased to 100  mg / hr every 30 minutes to maximum of 400  mg / hr . additionally it is recommended to premedicate with acetaminophen and an antihistamine prior to each rituximab dose .
subsequent infusions may be given at a faster rate , but they may take up to 4 hours to infuse .
rituximab therapy in the maintenance setting has shown to improve progression - free survival and overall survival .
maintenance rituximab can be administered according to several different schedules including one dose every 2 months , one dose every 3 months , or once weekly for 4 doses every 6 months [ 4 , 5 ] .
studies have been conducted to determine the safety and feasibility of administering rapid rituximab ; however , these studies did not include patients receiving rituximab maintenance for low - grade non - hodgkin 's lymphoma [ 3 , 68 ] .
herein , we present our experience at h. lee moffitt cancer center with rapid infusion rituximab administered as maintenance therapy for low - grade non - hodgkin 's lymphoma .
h. lee moffitt cancer center has been utilizing a rapid rituximab infusion protocol since december 2007 .
the rapid infusion rituximab protocol indicates to infuse rituximab at a rate of 150  ml / hr for 30 minutes then increase the rate to 275 
this method is used to prevent rate calculation errors and ensures all infusions are infused over 90 minutes ( 5 minutes ) for doses between 500  mg and 1000  mg .
additionally methylprednisolone , hydromorphone , diphenhydramine and epinephrine are available in the event of an infusion - related reaction .
if symptoms of a reaction occur , the infusion is stopped until symptoms resolve and is resumed at 50% of the previous rate and titrated every 30 minutes as tolerated .
patients must meet the following criteria in order to be eligible for rapid infusion rituximab : rituximab courses two to eight prescribed at standard doses given concurrently with chemotherapy , no grade 3/4 toxicity with previous course , subsequent rituximab monotherapy courses if no grade 3/4 toxicity with initial two courses , peripheral lymphocyte count < 4.8  k / ul , maintenance chemotherapy , following response to induction to chemotherapy.this retrospective analysis included patients diagnosed with low - grade non - hodgkin 's lymphoma who received rapid infusion rituximab for maintenance therapy from december 2007 through november 2011 .
patients were included if they were greater than 18 years of age , met eligibility requirements to receive rapid infusion rituximab per moffitt protocol , and diagnosed with low - grade non - hodgkin 's lymphoma .
data collection included diagnosis , treatment regimen prior to maintenance therapy , rituximab maintenance schedule , administration of premedications , and any adverse events .
adverse events were evaluated through documentation , vital signs , and administration of supportive care .
the primary objective of this retrospective analysis was to evaluate the incidence of grade 3 and grade 4 toxicities with maintenance rapid infusion rituximab according to the common terminology criteria for adverse events version 4 .
secondary objectives included evaluating all infusion - related adverse events ( grades 14 ) with maintenance rituximab and evaluating correlation of adverse events with varying schedules of rituximab maintenance therapy .
rituximab courses two to eight prescribed at standard doses given concurrently with chemotherapy , no grade 3/4 toxicity with previous course , subsequent rituximab monotherapy courses if no grade 3/4 toxicity with initial two courses , peripheral lymphocyte count
< 4.8  k / ul , maintenance chemotherapy , following response to induction to chemotherapy .
a total of 1,070 patients received rituximab as part of their treatment regimen from december 1 , 2007 through november 25 , 2011 .
rapid rate maintenance rituximab therapy was given to 109 patients for a total of 647 doses .
all of the patients received premedication with acetaminophen and an antihistamine as directed by the package insert .
patients who had a prior infusion - related reaction with rituximab premedicated with corticosteroids in addition to acetaminophen and diphenhydramine .
each patient received an average of six doses of maintenance rituximab therapy at a rapid infusion rate , and the average infusion time for each dose administered was approximately ninety minutes .
administration of rituximab at a rapid rate saved approximately 68 minutes per patient ( table 1 ) .
the majority of patients ( 64% ) were diagnosed with follicular lymphoma and 8% had an unspecified low - grade lymphoma .
the remainder of patients were diagnosed with one of the following low - grade lymphomas : mantle cell lymphoma , marginal zone lymphoma , mucosa - associated lymphoid tissue ( malt ) , small lymphocytic leukemia , and chronic lymphocytic leukemia ( figure 1 ) .
a small minority of patients received rituximab maintenance regimen every two months based on data published from the prima study   ( figure 2 ) . out of the 109 patients analyzed ,
3 patients developed an infusion - related reaction including one patient who developed a reaction twice .
two of the patients required pharmacological management with corticosteroids , additional antihistamines , and/or inhaled beta - agonists .
this analysis supports that rituximab can be safely administered as a rapid infusion during maintenance therapy .
our experience resulted in a low incidence of grade 3 reactions and no grade 4 reactions .
the data also reveals the incidence of developing a grade 2 reaction is quite low . out of the 109 patients analyzed ,
one patient experienced nausea ( grade 1 ) with the first dose of the 3rd cycle of maintenance therapy .
the other two patients experienced symptoms such as shortness of breath , facial flushing , and chest tightness ( grade 3 ) ( table 3 ) .
two of the patients were rechallenged at the rapid rate and tolerated therapy without further complications . in the patients who developed a grade 3 reaction , the incidence was too low to determine a correlation with the administration schedule of maintenance therapy .
when rituximab is administered at the standard rate , the patient 's infusion time may last up to 6 hours .
longer administration time is inconvenient for the patient as well as nurses . with implementation of the rapid infusion method
as previously mentioned , h. lee moffitt cancer center administers rapid infusion rituximab at an initial rate of 150  ml / hr for 30 minutes followed by an increase of the rate to 275  ml / hr until completion of infusion .
our method of infusion varies from the package insert recommendation ; however , the average infusion time was 90 minutes for our patients . with our method , over one hour of chair time
rapid rituximab infusion improves the turn - around time for each patient and decreases resource utilization in the infusion center .   with the low incidence of infusion - related reactions in combination with short administration time
 rituximab is an anti - cd-20 monoclonal antibody used in the management of lymphoproliferative disorders . 
 the use of maintenance rituximab has improved progression free survival and overall survival in follicular lymphomas . although rapid rituximab infusions have been studied extensively , 
 there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas . 
 the primary objective of this retrospective analysis was to evaluate the incidence of grade 3 and 4 toxicities with maintenance rapid infusion rituximab according to the common terminology criteria for adverse events version 4 ( ctc v. 4 ) . 
 secondary objectives included evaluating all grade infusion related adverse events and correlation of adverse events with varying schedules of rituximab maintenance therapy . 
 all patients who received rapid infusion rituximab as maintenance therapy for low grade lymphoma between december 2007 and november 2011 were included . 
 rapid rituximab infusions were administered over 90 minutes . 
 demographic , laboratory and clinical data were collected . 
 a total of 109 patients received 647 rapid rituximab infusions . 
 three patients experienced an adverse reaction which resulted in one grade 1 infusion reaction and three grade 3 infusion reactions . 
 no patients required hospitalization . 
 all 3 patients received pharmacological and/or supportive care to relieve symptoms associated with the reaction . 
 
1. Introduction
2. Methods
3. Results
4. Discussion