Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial
In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an atte...
Gespeichert in:
| Veröffentlicht in: | Journal of clinical oncology 2012-05, Vol.30 (14), p.1647-1655 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1655 |
|---|---|
| container_issue | 14 |
| container_start_page | 1647 |
| container_title | Journal of clinical oncology |
| container_volume | 30 |
| creator | PETTITT, Andrew R JACKSON, Richard CATOVSKY, Daniel RADFORD, John A BLOOR, Adrian FOLLOWS, George A DEVEREUX, Stephen KRUGER, Anton BLUNDELL, Julie AGRAWAL, Samir ALLSUP, David PROCTOR, Stephen CARRUTHERS, Stacey HEARTIN, Earnest OSCIER, David HAMBLIN, Terry J RAWSTRON, Andrew HILLMEN, Peter DODD, James DODD, Susanna OATES, Melanie JOHNSON, Gillian G SCHUH, Anna MATUTES, Estella DEARDEN, Claire E |
| description | In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.
Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS).
The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%.
Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide. |
| doi_str_mv | 10.1200/JCO.2011.35.9695 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1551645671</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1017959474</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-5aa5bebc3bf08ca0158e5882b6de14fd610d7de62aa7627519ec94e33eb5237b3</originalsourceid><addsrcrecordid>eNqFkktv1DAURiMEokNhzwp5g2CTwY84TthVoaVFA63QINhFjnPTuDj2YDug4ffyQ_A8gCUrW9fnHn22b5Y9JXhJKMav3jXXS4oJWTK-rMua38sWhFORC8H5_WyBBaM5qdiXk-xRCHcYk6Ji_GF2QmlRs4KwRfbrzMAU55_zJDukLWrc1Gkro3YWfdZxRO8hjluz8dBbHZxxFtBVQBJd6tvRbNH5MICK-nuq2n5W-76PcKsnsGhwHt0kFdgYDrJm9M5qhVbbaTM6tY27PcxfYdISSdujN2Bg73ADWt9w9hpdpDQmKcNskiWV4wjowz5gqjfSKvC7Y5BejSlEiDrOEVCzWlFcorXX0jzOHgzSBHhyXE-zTxfn6-YyX12_vWrOVrkqRBFzLiXvoFOsG3ClJCa8Al5VtCt7IMXQlwT3ooeSSilKKjipQdUFMAYdp0x07DR7efBuvPs2Q4jtpIMCY6QFN4eWcE7KgpeC_B_FRNS8TrkSig-o8i4ED0O78XqSfpugdjcGbRqDdjcGLePtbgxSy7Ojfe4m6P82_Pn3BDw_AjIoaQaf3lGHfxyvSpoCJO7FgRvTd__QHtowSWOSlrZ3yrEUoGjTnQT7Df9dyxQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1017959474</pqid></control><display><type>article</type><title>Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial</title><source>MEDLINE</source><source>American Society of Clinical Oncology Online Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>PETTITT, Andrew R ; JACKSON, Richard ; CATOVSKY, Daniel ; RADFORD, John A ; BLOOR, Adrian ; FOLLOWS, George A ; DEVEREUX, Stephen ; KRUGER, Anton ; BLUNDELL, Julie ; AGRAWAL, Samir ; ALLSUP, David ; PROCTOR, Stephen ; CARRUTHERS, Stacey ; HEARTIN, Earnest ; OSCIER, David ; HAMBLIN, Terry J ; RAWSTRON, Andrew ; HILLMEN, Peter ; DODD, James ; DODD, Susanna ; OATES, Melanie ; JOHNSON, Gillian G ; SCHUH, Anna ; MATUTES, Estella ; DEARDEN, Claire E</creator><creatorcontrib>PETTITT, Andrew R ; JACKSON, Richard ; CATOVSKY, Daniel ; RADFORD, John A ; BLOOR, Adrian ; FOLLOWS, George A ; DEVEREUX, Stephen ; KRUGER, Anton ; BLUNDELL, Julie ; AGRAWAL, Samir ; ALLSUP, David ; PROCTOR, Stephen ; CARRUTHERS, Stacey ; HEARTIN, Earnest ; OSCIER, David ; HAMBLIN, Terry J ; RAWSTRON, Andrew ; HILLMEN, Peter ; DODD, James ; DODD, Susanna ; OATES, Melanie ; JOHNSON, Gillian G ; SCHUH, Anna ; MATUTES, Estella ; DEARDEN, Claire E</creatorcontrib><description>In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.
Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS).
The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%.
Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.2011.35.9695</identifier><identifier>PMID: 22493413</identifier><language>eng</language><publisher>Alexandria, VA: American Society of Clinical Oncology</publisher><subject>Academies and Institutes ; Adult ; Age ; Aged ; Aged, 80 and over ; Alemtuzumab ; Antibiotic Prophylaxis - methods ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antimicrobial agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Chronic lymphatic leukemia ; Clinical trials ; cotrimoxazole ; Cyclophosphamide ; Cytomegalovirus ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; fludarabine ; Follow-Up Studies ; Gene Deletion ; Genes, p53 - genetics ; Hematologic and hematopoietic diseases ; Humans ; Itraconazole ; Kaplan-Meier Estimate ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Logistic Models ; Male ; Medical sciences ; methylprednisolone ; Methylprednisolone - administration & dosage ; Middle Aged ; Monoclonal antibodies ; Mortality ; Mutation ; p53 protein ; Prophylaxis ; Proportional Hazards Models ; Remission Induction ; Risk Assessment ; rituximab ; Survival ; Survival Rate ; Toxicity ; Treatment Outcome ; Tumors ; United Kingdom ; Viremia</subject><ispartof>Journal of clinical oncology, 2012-05, Vol.30 (14), p.1647-1655</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-5aa5bebc3bf08ca0158e5882b6de14fd610d7de62aa7627519ec94e33eb5237b3</citedby><cites>FETCH-LOGICAL-c474t-5aa5bebc3bf08ca0158e5882b6de14fd610d7de62aa7627519ec94e33eb5237b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3733,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25862179$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22493413$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PETTITT, Andrew R</creatorcontrib><creatorcontrib>JACKSON, Richard</creatorcontrib><creatorcontrib>CATOVSKY, Daniel</creatorcontrib><creatorcontrib>RADFORD, John A</creatorcontrib><creatorcontrib>BLOOR, Adrian</creatorcontrib><creatorcontrib>FOLLOWS, George A</creatorcontrib><creatorcontrib>DEVEREUX, Stephen</creatorcontrib><creatorcontrib>KRUGER, Anton</creatorcontrib><creatorcontrib>BLUNDELL, Julie</creatorcontrib><creatorcontrib>AGRAWAL, Samir</creatorcontrib><creatorcontrib>ALLSUP, David</creatorcontrib><creatorcontrib>PROCTOR, Stephen</creatorcontrib><creatorcontrib>CARRUTHERS, Stacey</creatorcontrib><creatorcontrib>HEARTIN, Earnest</creatorcontrib><creatorcontrib>OSCIER, David</creatorcontrib><creatorcontrib>HAMBLIN, Terry J</creatorcontrib><creatorcontrib>RAWSTRON, Andrew</creatorcontrib><creatorcontrib>HILLMEN, Peter</creatorcontrib><creatorcontrib>DODD, James</creatorcontrib><creatorcontrib>DODD, Susanna</creatorcontrib><creatorcontrib>OATES, Melanie</creatorcontrib><creatorcontrib>JOHNSON, Gillian G</creatorcontrib><creatorcontrib>SCHUH, Anna</creatorcontrib><creatorcontrib>MATUTES, Estella</creatorcontrib><creatorcontrib>DEARDEN, Claire E</creatorcontrib><title>Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.
Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS).
The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%.
Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.</description><subject>Academies and Institutes</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alemtuzumab</subject><subject>Antibiotic Prophylaxis - methods</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antimicrobial agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Chronic lymphatic leukemia</subject><subject>Clinical trials</subject><subject>cotrimoxazole</subject><subject>Cyclophosphamide</subject><subject>Cytomegalovirus</subject><subject>Disease-Free Survival</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>fludarabine</subject><subject>Follow-Up Studies</subject><subject>Gene Deletion</subject><subject>Genes, p53 - genetics</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Itraconazole</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>methylprednisolone</subject><subject>Methylprednisolone - administration & dosage</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Mortality</subject><subject>Mutation</subject><subject>p53 protein</subject><subject>Prophylaxis</subject><subject>Proportional Hazards Models</subject><subject>Remission Induction</subject><subject>Risk Assessment</subject><subject>rituximab</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>United Kingdom</subject><subject>Viremia</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAURiMEokNhzwp5g2CTwY84TthVoaVFA63QINhFjnPTuDj2YDug4ffyQ_A8gCUrW9fnHn22b5Y9JXhJKMav3jXXS4oJWTK-rMua38sWhFORC8H5_WyBBaM5qdiXk-xRCHcYk6Ji_GF2QmlRs4KwRfbrzMAU55_zJDukLWrc1Gkro3YWfdZxRO8hjluz8dBbHZxxFtBVQBJd6tvRbNH5MICK-nuq2n5W-76PcKsnsGhwHt0kFdgYDrJm9M5qhVbbaTM6tY27PcxfYdISSdujN2Bg73ADWt9w9hpdpDQmKcNskiWV4wjowz5gqjfSKvC7Y5BejSlEiDrOEVCzWlFcorXX0jzOHgzSBHhyXE-zTxfn6-YyX12_vWrOVrkqRBFzLiXvoFOsG3ClJCa8Al5VtCt7IMXQlwT3ooeSSilKKjipQdUFMAYdp0x07DR7efBuvPs2Q4jtpIMCY6QFN4eWcE7KgpeC_B_FRNS8TrkSig-o8i4ED0O78XqSfpugdjcGbRqDdjcGLePtbgxSy7Ojfe4m6P82_Pn3BDw_AjIoaQaf3lGHfxyvSpoCJO7FgRvTd__QHtowSWOSlrZ3yrEUoGjTnQT7Df9dyxQ</recordid><startdate>20120510</startdate><enddate>20120510</enddate><creator>PETTITT, Andrew R</creator><creator>JACKSON, Richard</creator><creator>CATOVSKY, Daniel</creator><creator>RADFORD, John A</creator><creator>BLOOR, Adrian</creator><creator>FOLLOWS, George A</creator><creator>DEVEREUX, Stephen</creator><creator>KRUGER, Anton</creator><creator>BLUNDELL, Julie</creator><creator>AGRAWAL, Samir</creator><creator>ALLSUP, David</creator><creator>PROCTOR, Stephen</creator><creator>CARRUTHERS, Stacey</creator><creator>HEARTIN, Earnest</creator><creator>OSCIER, David</creator><creator>HAMBLIN, Terry J</creator><creator>RAWSTRON, Andrew</creator><creator>HILLMEN, Peter</creator><creator>DODD, James</creator><creator>DODD, Susanna</creator><creator>OATES, Melanie</creator><creator>JOHNSON, Gillian G</creator><creator>SCHUH, Anna</creator><creator>MATUTES, Estella</creator><creator>DEARDEN, Claire E</creator><general>American Society of Clinical Oncology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20120510</creationdate><title>Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial</title><author>PETTITT, Andrew R ; JACKSON, Richard ; CATOVSKY, Daniel ; RADFORD, John A ; BLOOR, Adrian ; FOLLOWS, George A ; DEVEREUX, Stephen ; KRUGER, Anton ; BLUNDELL, Julie ; AGRAWAL, Samir ; ALLSUP, David ; PROCTOR, Stephen ; CARRUTHERS, Stacey ; HEARTIN, Earnest ; OSCIER, David ; HAMBLIN, Terry J ; RAWSTRON, Andrew ; HILLMEN, Peter ; DODD, James ; DODD, Susanna ; OATES, Melanie ; JOHNSON, Gillian G ; SCHUH, Anna ; MATUTES, Estella ; DEARDEN, Claire E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-5aa5bebc3bf08ca0158e5882b6de14fd610d7de62aa7627519ec94e33eb5237b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Academies and Institutes</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alemtuzumab</topic><topic>Antibiotic Prophylaxis - methods</topic><topic>Antibodies, Monoclonal, Humanized - administration & dosage</topic><topic>Antimicrobial agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Chronic lymphatic leukemia</topic><topic>Clinical trials</topic><topic>cotrimoxazole</topic><topic>Cyclophosphamide</topic><topic>Cytomegalovirus</topic><topic>Disease-Free Survival</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>fludarabine</topic><topic>Follow-Up Studies</topic><topic>Gene Deletion</topic><topic>Genes, p53 - genetics</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Itraconazole</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>methylprednisolone</topic><topic>Methylprednisolone - administration & dosage</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Mortality</topic><topic>Mutation</topic><topic>p53 protein</topic><topic>Prophylaxis</topic><topic>Proportional Hazards Models</topic><topic>Remission Induction</topic><topic>Risk Assessment</topic><topic>rituximab</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Toxicity</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>United Kingdom</topic><topic>Viremia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PETTITT, Andrew R</creatorcontrib><creatorcontrib>JACKSON, Richard</creatorcontrib><creatorcontrib>CATOVSKY, Daniel</creatorcontrib><creatorcontrib>RADFORD, John A</creatorcontrib><creatorcontrib>BLOOR, Adrian</creatorcontrib><creatorcontrib>FOLLOWS, George A</creatorcontrib><creatorcontrib>DEVEREUX, Stephen</creatorcontrib><creatorcontrib>KRUGER, Anton</creatorcontrib><creatorcontrib>BLUNDELL, Julie</creatorcontrib><creatorcontrib>AGRAWAL, Samir</creatorcontrib><creatorcontrib>ALLSUP, David</creatorcontrib><creatorcontrib>PROCTOR, Stephen</creatorcontrib><creatorcontrib>CARRUTHERS, Stacey</creatorcontrib><creatorcontrib>HEARTIN, Earnest</creatorcontrib><creatorcontrib>OSCIER, David</creatorcontrib><creatorcontrib>HAMBLIN, Terry J</creatorcontrib><creatorcontrib>RAWSTRON, Andrew</creatorcontrib><creatorcontrib>HILLMEN, Peter</creatorcontrib><creatorcontrib>DODD, James</creatorcontrib><creatorcontrib>DODD, Susanna</creatorcontrib><creatorcontrib>OATES, Melanie</creatorcontrib><creatorcontrib>JOHNSON, Gillian G</creatorcontrib><creatorcontrib>SCHUH, Anna</creatorcontrib><creatorcontrib>MATUTES, Estella</creatorcontrib><creatorcontrib>DEARDEN, Claire E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PETTITT, Andrew R</au><au>JACKSON, Richard</au><au>CATOVSKY, Daniel</au><au>RADFORD, John A</au><au>BLOOR, Adrian</au><au>FOLLOWS, George A</au><au>DEVEREUX, Stephen</au><au>KRUGER, Anton</au><au>BLUNDELL, Julie</au><au>AGRAWAL, Samir</au><au>ALLSUP, David</au><au>PROCTOR, Stephen</au><au>CARRUTHERS, Stacey</au><au>HEARTIN, Earnest</au><au>OSCIER, David</au><au>HAMBLIN, Terry J</au><au>RAWSTRON, Andrew</au><au>HILLMEN, Peter</au><au>DODD, James</au><au>DODD, Susanna</au><au>OATES, Melanie</au><au>JOHNSON, Gillian G</au><au>SCHUH, Anna</au><au>MATUTES, Estella</au><au>DEARDEN, Claire E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2012-05-10</date><risdate>2012</risdate><volume>30</volume><issue>14</issue><spage>1647</spage><epage>1655</epage><pages>1647-1655</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination.
Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS).
The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%.
Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.</abstract><cop>Alexandria, VA</cop><pub>American Society of Clinical Oncology</pub><pmid>22493413</pmid><doi>10.1200/JCO.2011.35.9695</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0732-183X |
| ispartof | Journal of clinical oncology, 2012-05, Vol.30 (14), p.1647-1655 |
| issn | 0732-183X 1527-7755 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1551645671 |
| source | MEDLINE; American Society of Clinical Oncology Online Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Academies and Institutes Adult Age Aged Aged, 80 and over Alemtuzumab Antibiotic Prophylaxis - methods Antibodies, Monoclonal, Humanized - administration & dosage Antimicrobial agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Chronic lymphatic leukemia Clinical trials cotrimoxazole Cyclophosphamide Cytomegalovirus Disease-Free Survival Dose-Response Relationship, Drug Drug Administration Schedule Female fludarabine Follow-Up Studies Gene Deletion Genes, p53 - genetics Hematologic and hematopoietic diseases Humans Itraconazole Kaplan-Meier Estimate Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - mortality Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Logistic Models Male Medical sciences methylprednisolone Methylprednisolone - administration & dosage Middle Aged Monoclonal antibodies Mortality Mutation p53 protein Prophylaxis Proportional Hazards Models Remission Induction Risk Assessment rituximab Survival Survival Rate Toxicity Treatment Outcome Tumors United Kingdom Viremia |
| title | Alemtuzumab in Combination With Methylprednisolone Is a Highly Effective Induction Regimen for Patients With Chronic Lymphocytic Leukemia and Deletion of TP53: Final Results of the National Cancer Research Institute CLL206 Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T08%3A58%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alemtuzumab%20in%20Combination%20With%20Methylprednisolone%20Is%20a%20Highly%20Effective%20Induction%20Regimen%20for%20Patients%20With%20Chronic%20Lymphocytic%20Leukemia%20and%20Deletion%20of%20TP53:%20Final%20Results%20of%20the%20National%20Cancer%20Research%20Institute%20CLL206%20Trial&rft.jtitle=Journal%20of%20clinical%20oncology&rft.au=PETTITT,%20Andrew%20R&rft.date=2012-05-10&rft.volume=30&rft.issue=14&rft.spage=1647&rft.epage=1655&rft.pages=1647-1655&rft.issn=0732-183X&rft.eissn=1527-7755&rft_id=info:doi/10.1200/JCO.2011.35.9695&rft_dat=%3Cproquest_cross%3E1017959474%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1017959474&rft_id=info:pmid/22493413&rfr_iscdi=true |