FRI0155 Rituximab Associated Late Onset Neutropaenia: Safety of Retreatment Rituximab Therapy in 900 Patients
BackgroundNeutropaenia is reported as a complication of rituximab (RTX) therapy for B cell malignancies with an incidence of 3-27%. [1] Data in rheumatic diseases are more limited and the optimal management of these patients has not been defined.ObjectivesThe aims of this study were to determine the...
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| Veröffentlicht in: | Annals of the rheumatic diseases 2015-06, Vol.74 (Suppl 2), p.479 |
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| description | BackgroundNeutropaenia is reported as a complication of rituximab (RTX) therapy for B cell malignancies with an incidence of 3-27%. [1] Data in rheumatic diseases are more limited and the optimal management of these patients has not been defined.ObjectivesThe aims of this study were to determine the (1) incidence of rituximab-associated neutropaenia; (2) rates of infection; (3) time for recovery; (4) safety of retreatment with RTX, as a basis for management guidelines.MethodsWe conducted an observational study on all patients treated with RTX in a single centre between 2003 and 2014. Each cycle consisted of 2x1000mg (with a small percentage receiving half dose if in remission), repeated either on clinical relapse or pre-emptively. RAN was defined as an absolute neutrophil count 1.0×109/L), moderate (0.5-1.0×109/L) and severe (0.5 x 109/L was associated with infection. Irrespective of the degree of neutropaenia, all patients responded to RTX for the original indication. 26 (72.2%) of the episodes had complete B cell depletion as assessed by highly sensitive FACS. Of the patients who were retreated with RTX 2x1000mg: 11/19 had no recurrence of neutropaenia, 8/19 had mild neutropaenia in next cycle, and 4 patients had again recurrence of mild neutropenia. All the subsequent episodes were without |
| doi_str_mv | 10.1136/annrheumdis-2015-eular.3881 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1901807661</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4322507657</sourcerecordid><originalsourceid>FETCH-LOGICAL-b1851-19d93eb09b24cc84da72c611d6361738a5992de06813ad666bf3af574e61ac1f3</originalsourceid><addsrcrecordid>eNqVkM9Kw0AQxhdRsFbfYaHn1J1sstnoqRSrhWKl1vOySSY0pfnj7gbszYsv6pO4tYJevcwww_d9M_wIGQEbA3BxrZvGbLCvi8oGIYM4wH6nzZhLCSdkAJGQfi3YKRkwxngQpSI5JxfWbv3IJMgBaWeruTfGn-8fq8r1b1WtMzqxts0r7bCgC1_psrHo6CP2zrSdxqbSN_RZl-j2tC3pCp1B7WpsHP3NWG_Q6G5Pq4amjNEn7SovsJfkrNQ7i1c_fUheZnfr6UOwWN7Pp5NFkIGMIYC0SDlmLM3CKM9lVOgkzAVAIbiAhEsdp2lYIBMSuC6EEFnJdRknEQrQOZR8SEbH3M60rz1ap7Ztbxp_UkHKQLJECPCq26MqN621BkvVGf-92Stg6kBY_SGsDoTVN2F1IOzd4ujO6u2_jF8q8Ifh</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1901807661</pqid></control><display><type>article</type><title>FRI0155 Rituximab Associated Late Onset Neutropaenia: Safety of Retreatment Rituximab Therapy in 900 Patients</title><source>BMJ Journals - NESLi2</source><creator>Ferreira, J.F. ; Md Yusof, M.Y. ; Das, S. ; Vital, E.M. ; Emery, P.</creator><creatorcontrib>Ferreira, J.F. ; Md Yusof, M.Y. ; Das, S. ; Vital, E.M. ; Emery, P.</creatorcontrib><description>BackgroundNeutropaenia is reported as a complication of rituximab (RTX) therapy for B cell malignancies with an incidence of 3-27%. [1] Data in rheumatic diseases are more limited and the optimal management of these patients has not been defined.ObjectivesThe aims of this study were to determine the (1) incidence of rituximab-associated neutropaenia; (2) rates of infection; (3) time for recovery; (4) safety of retreatment with RTX, as a basis for management guidelines.MethodsWe conducted an observational study on all patients treated with RTX in a single centre between 2003 and 2014. Each cycle consisted of 2x1000mg (with a small percentage receiving half dose if in remission), repeated either on clinical relapse or pre-emptively. RAN was defined as an absolute neutrophil count <2.0×109/L occurring at least 4 weeks after RTX excluding chronic neutropaenia or alternative plausible explanation (e.g. Felty's syndrome).ResultsRituximab-associated neutropaenia was identified in 23 patients (2.5%) from a cohort of 912, and in 36 cycles (1.2%) out of 3062 administered. 20 patients were female; median (IQR) age 61 (54-68,2) years. 19 had rheumatoid arthritis (RA) (2.72% of all RA patients in this cohort), 1 SLE, 1 cryoglobulinemia, 1 Sjogren's syndrome and 1 GPA. 21 patient received concomitant methotrexate, 1 SLE patient received cyclophosphamide and 1 RA patient received hydroxychloroquine. Neutropaenia occurred at median 17 weeks (range 4-31) following RTX infusion and median 3nd cycle (range 1-9). The majority of neutropenic episodes were transient; neutrophil count was normal on the first repeat test in 24 (66.7%) of the episodes. The frequency of mild (>1.0×109/L), moderate (0.5-1.0×109/L) and severe (<0.5×109/L) neutropaenia were 18 (50%), 6 (16.7%) and 12 (32.3%) episodes respectively. Of these, 10 infections requiring antibiotics were recorded in severe neutropenia cases, most commonly chest infection (6 also required granulocyte-colony stimulating factor (GCSF)). No case of neutropaenia >0.5 x 109/L was associated with infection. Irrespective of the degree of neutropaenia, all patients responded to RTX for the original indication. 26 (72.2%) of the episodes had complete B cell depletion as assessed by highly sensitive FACS. Of the patients who were retreated with RTX 2x1000mg: 11/19 had no recurrence of neutropaenia, 8/19 had mild neutropaenia in next cycle, and 4 patients had again recurrence of mild neutropenia. All the subsequent episodes were without associated infection or requirement for GCSF.ConclusionsThis is the largest cohort analysed for rituximab-associated neutropaenia. It can be concluded: (1) at <3%, it is less common in rheumatic disease than lymphoma; (2) monitoring alone is appropriate unless there is evidence of infection, when GCSF may be required; (3) the majority of the neutropenia cases recovered promptly; (4) counts >0.5 x109/L had no infections; (5) on retreatment, mild neutropaenia recurred in less than half with few consequences, with no evidence for neutropaenia becoming more severe on repeat cycles; (6) it therefore appears retreatment with monitoring is appropriate with caution only in severely neutropenic patients. The aetiology of rituximab-associated neutropaenia needs further investigation.ReferencesTesfa D, Expert Rev. Hematol, 2011Disclosure of InterestJ. Ferreira: None declared, M. Y. Md Yusof: None declared, S. Das: None declared, E. Vital Grant/research support from: Roche and GSK., P. Emery Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Consultant for: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2015-eular.3881</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>Kidlington: Elsevier Limited</publisher><ispartof>Annals of the rheumatic diseases, 2015-06, Vol.74 (Suppl 2), p.479</ispartof><rights>2015, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Copyright: 2015 (c) 2015, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b1851-19d93eb09b24cc84da72c611d6361738a5992de06813ad666bf3af574e61ac1f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/74/Suppl_2/479.1.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/74/Suppl_2/479.1.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,77569,77600</link.rule.ids></links><search><creatorcontrib>Ferreira, J.F.</creatorcontrib><creatorcontrib>Md Yusof, M.Y.</creatorcontrib><creatorcontrib>Das, S.</creatorcontrib><creatorcontrib>Vital, E.M.</creatorcontrib><creatorcontrib>Emery, P.</creatorcontrib><title>FRI0155 Rituximab Associated Late Onset Neutropaenia: Safety of Retreatment Rituximab Therapy in 900 Patients</title><title>Annals of the rheumatic diseases</title><description>BackgroundNeutropaenia is reported as a complication of rituximab (RTX) therapy for B cell malignancies with an incidence of 3-27%. [1] Data in rheumatic diseases are more limited and the optimal management of these patients has not been defined.ObjectivesThe aims of this study were to determine the (1) incidence of rituximab-associated neutropaenia; (2) rates of infection; (3) time for recovery; (4) safety of retreatment with RTX, as a basis for management guidelines.MethodsWe conducted an observational study on all patients treated with RTX in a single centre between 2003 and 2014. Each cycle consisted of 2x1000mg (with a small percentage receiving half dose if in remission), repeated either on clinical relapse or pre-emptively. RAN was defined as an absolute neutrophil count <2.0×109/L occurring at least 4 weeks after RTX excluding chronic neutropaenia or alternative plausible explanation (e.g. Felty's syndrome).ResultsRituximab-associated neutropaenia was identified in 23 patients (2.5%) from a cohort of 912, and in 36 cycles (1.2%) out of 3062 administered. 20 patients were female; median (IQR) age 61 (54-68,2) years. 19 had rheumatoid arthritis (RA) (2.72% of all RA patients in this cohort), 1 SLE, 1 cryoglobulinemia, 1 Sjogren's syndrome and 1 GPA. 21 patient received concomitant methotrexate, 1 SLE patient received cyclophosphamide and 1 RA patient received hydroxychloroquine. Neutropaenia occurred at median 17 weeks (range 4-31) following RTX infusion and median 3nd cycle (range 1-9). The majority of neutropenic episodes were transient; neutrophil count was normal on the first repeat test in 24 (66.7%) of the episodes. The frequency of mild (>1.0×109/L), moderate (0.5-1.0×109/L) and severe (<0.5×109/L) neutropaenia were 18 (50%), 6 (16.7%) and 12 (32.3%) episodes respectively. Of these, 10 infections requiring antibiotics were recorded in severe neutropenia cases, most commonly chest infection (6 also required granulocyte-colony stimulating factor (GCSF)). No case of neutropaenia >0.5 x 109/L was associated with infection. Irrespective of the degree of neutropaenia, all patients responded to RTX for the original indication. 26 (72.2%) of the episodes had complete B cell depletion as assessed by highly sensitive FACS. Of the patients who were retreated with RTX 2x1000mg: 11/19 had no recurrence of neutropaenia, 8/19 had mild neutropaenia in next cycle, and 4 patients had again recurrence of mild neutropenia. All the subsequent episodes were without associated infection or requirement for GCSF.ConclusionsThis is the largest cohort analysed for rituximab-associated neutropaenia. It can be concluded: (1) at <3%, it is less common in rheumatic disease than lymphoma; (2) monitoring alone is appropriate unless there is evidence of infection, when GCSF may be required; (3) the majority of the neutropenia cases recovered promptly; (4) counts >0.5 x109/L had no infections; (5) on retreatment, mild neutropaenia recurred in less than half with few consequences, with no evidence for neutropaenia becoming more severe on repeat cycles; (6) it therefore appears retreatment with monitoring is appropriate with caution only in severely neutropenic patients. The aetiology of rituximab-associated neutropaenia needs further investigation.ReferencesTesfa D, Expert Rev. Hematol, 2011Disclosure of InterestJ. Ferreira: None declared, M. Y. Md Yusof: None declared, S. Das: None declared, E. Vital Grant/research support from: Roche and GSK., P. Emery Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Consultant for: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB.</description><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqVkM9Kw0AQxhdRsFbfYaHn1J1sstnoqRSrhWKl1vOySSY0pfnj7gbszYsv6pO4tYJevcwww_d9M_wIGQEbA3BxrZvGbLCvi8oGIYM4wH6nzZhLCSdkAJGQfi3YKRkwxngQpSI5JxfWbv3IJMgBaWeruTfGn-8fq8r1b1WtMzqxts0r7bCgC1_psrHo6CP2zrSdxqbSN_RZl-j2tC3pCp1B7WpsHP3NWG_Q6G5Pq4amjNEn7SovsJfkrNQ7i1c_fUheZnfr6UOwWN7Pp5NFkIGMIYC0SDlmLM3CKM9lVOgkzAVAIbiAhEsdp2lYIBMSuC6EEFnJdRknEQrQOZR8SEbH3M60rz1ap7Ztbxp_UkHKQLJECPCq26MqN621BkvVGf-92Stg6kBY_SGsDoTVN2F1IOzd4ujO6u2_jF8q8Ifh</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Ferreira, J.F.</creator><creator>Md Yusof, M.Y.</creator><creator>Das, S.</creator><creator>Vital, E.M.</creator><creator>Emery, P.</creator><general>Elsevier Limited</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>201506</creationdate><title>FRI0155 Rituximab Associated Late Onset Neutropaenia: Safety of Retreatment Rituximab Therapy in 900 Patients</title><author>Ferreira, J.F. ; Md Yusof, M.Y. ; Das, S. ; Vital, E.M. ; Emery, P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1851-19d93eb09b24cc84da72c611d6361738a5992de06813ad666bf3af574e61ac1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferreira, J.F.</creatorcontrib><creatorcontrib>Md Yusof, M.Y.</creatorcontrib><creatorcontrib>Das, S.</creatorcontrib><creatorcontrib>Vital, E.M.</creatorcontrib><creatorcontrib>Emery, P.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferreira, J.F.</au><au>Md Yusof, M.Y.</au><au>Das, S.</au><au>Vital, E.M.</au><au>Emery, P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FRI0155 Rituximab Associated Late Onset Neutropaenia: Safety of Retreatment Rituximab Therapy in 900 Patients</atitle><jtitle>Annals of the rheumatic diseases</jtitle><date>2015-06</date><risdate>2015</risdate><volume>74</volume><issue>Suppl 2</issue><spage>479</spage><pages>479-</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>BackgroundNeutropaenia is reported as a complication of rituximab (RTX) therapy for B cell malignancies with an incidence of 3-27%. [1] Data in rheumatic diseases are more limited and the optimal management of these patients has not been defined.ObjectivesThe aims of this study were to determine the (1) incidence of rituximab-associated neutropaenia; (2) rates of infection; (3) time for recovery; (4) safety of retreatment with RTX, as a basis for management guidelines.MethodsWe conducted an observational study on all patients treated with RTX in a single centre between 2003 and 2014. Each cycle consisted of 2x1000mg (with a small percentage receiving half dose if in remission), repeated either on clinical relapse or pre-emptively. RAN was defined as an absolute neutrophil count <2.0×109/L occurring at least 4 weeks after RTX excluding chronic neutropaenia or alternative plausible explanation (e.g. Felty's syndrome).ResultsRituximab-associated neutropaenia was identified in 23 patients (2.5%) from a cohort of 912, and in 36 cycles (1.2%) out of 3062 administered. 20 patients were female; median (IQR) age 61 (54-68,2) years. 19 had rheumatoid arthritis (RA) (2.72% of all RA patients in this cohort), 1 SLE, 1 cryoglobulinemia, 1 Sjogren's syndrome and 1 GPA. 21 patient received concomitant methotrexate, 1 SLE patient received cyclophosphamide and 1 RA patient received hydroxychloroquine. Neutropaenia occurred at median 17 weeks (range 4-31) following RTX infusion and median 3nd cycle (range 1-9). The majority of neutropenic episodes were transient; neutrophil count was normal on the first repeat test in 24 (66.7%) of the episodes. The frequency of mild (>1.0×109/L), moderate (0.5-1.0×109/L) and severe (<0.5×109/L) neutropaenia were 18 (50%), 6 (16.7%) and 12 (32.3%) episodes respectively. Of these, 10 infections requiring antibiotics were recorded in severe neutropenia cases, most commonly chest infection (6 also required granulocyte-colony stimulating factor (GCSF)). No case of neutropaenia >0.5 x 109/L was associated with infection. Irrespective of the degree of neutropaenia, all patients responded to RTX for the original indication. 26 (72.2%) of the episodes had complete B cell depletion as assessed by highly sensitive FACS. Of the patients who were retreated with RTX 2x1000mg: 11/19 had no recurrence of neutropaenia, 8/19 had mild neutropaenia in next cycle, and 4 patients had again recurrence of mild neutropenia. All the subsequent episodes were without associated infection or requirement for GCSF.ConclusionsThis is the largest cohort analysed for rituximab-associated neutropaenia. It can be concluded: (1) at <3%, it is less common in rheumatic disease than lymphoma; (2) monitoring alone is appropriate unless there is evidence of infection, when GCSF may be required; (3) the majority of the neutropenia cases recovered promptly; (4) counts >0.5 x109/L had no infections; (5) on retreatment, mild neutropaenia recurred in less than half with few consequences, with no evidence for neutropaenia becoming more severe on repeat cycles; (6) it therefore appears retreatment with monitoring is appropriate with caution only in severely neutropenic patients. The aetiology of rituximab-associated neutropaenia needs further investigation.ReferencesTesfa D, Expert Rev. Hematol, 2011Disclosure of InterestJ. Ferreira: None declared, M. Y. Md Yusof: None declared, S. Das: None declared, E. Vital Grant/research support from: Roche and GSK., P. Emery Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Consultant for: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB.</abstract><cop>Kidlington</cop><pub>Elsevier Limited</pub><doi>10.1136/annrheumdis-2015-eular.3881</doi></addata></record> |
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| title | FRI0155 Rituximab Associated Late Onset Neutropaenia: Safety of Retreatment Rituximab Therapy in 900 Patients |
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