Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group
Summary Background In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of ear...
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| creator | Peyrade, Frédéric, Prof Bologna, Serge, MD Delwail, Vincent, MD Emile, Jean François, Prof Pascal, Laurent, MD Fermé, Christophe, MD Schiano, Jean-Marc, MD Coiffier, Bertrand, Prof Corront, Bernadette, MD Farhat, Hassan, MD Fruchart, Christophe, MD Ghesquieres, Herve, Prof Macro, Margaret, MD Tilly, Hervé, Prof Choufi, Bachra, MD Delarue, Richard, MD Fitoussi, Olivier, MD Gabarre, Jean, MD Haioun, Corinne, Prof Jardin, Fabrice, Prof |
| description | Summary Background In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. Methods For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m2 of intravenous doxorubicin, 400 mg/m2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov , number NCT01195714. Findings Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions. Interpretation Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and p |
| doi_str_mv | 10.1016/S2352-3026(16)30171-5 |
| format | Article |
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The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. Methods For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m2 of intravenous doxorubicin, 400 mg/m2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov , number NCT01195714. Findings Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions. Interpretation Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years. Funding The Lymphoma Study Association, GlaxoSmithKline.</description><identifier>ISSN: 2352-3026</identifier><identifier>EISSN: 2352-3026</identifier><identifier>DOI: 10.1016/S2352-3026(16)30171-5</identifier><identifier>PMID: 28041583</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject><![CDATA[Aged, 80 and over ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic Agents, Immunological - administration & dosage ; Antineoplastic Agents, Immunological - adverse effects ; Antineoplastic Agents, Immunological - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cyclophosphamide - administration & dosage ; Cyclophosphamide - adverse effects ; Cyclophosphamide - therapeutic use ; Doxorubicin - administration & dosage ; Doxorubicin - adverse effects ; Doxorubicin - therapeutic use ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Lymphoma, Large B-Cell, Diffuse - drug therapy ; Male ; Prednisone - administration & dosage ; Prednisone - adverse effects ; Prednisone - therapeutic use ; Sialic Acid Binding Ig-like Lectin 2 - antagonists & inhibitors ; Treatment Outcome ; Vincristine - administration & dosage ; Vincristine - adverse effects ; Vincristine - therapeutic use]]></subject><ispartof>The Lancet. Haematology, 2017, Vol.4 (1), p.e46-e55</ispartof><rights>Elsevier Ltd</rights><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-256a1f6e44dd4d5f0de1e532b828bab57ff80240a60b84f27809611c5700137c3</citedby><cites>FETCH-LOGICAL-c486t-256a1f6e44dd4d5f0de1e532b828bab57ff80240a60b84f27809611c5700137c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28041583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peyrade, Frédéric, Prof</creatorcontrib><creatorcontrib>Bologna, Serge, MD</creatorcontrib><creatorcontrib>Delwail, Vincent, MD</creatorcontrib><creatorcontrib>Emile, Jean François, Prof</creatorcontrib><creatorcontrib>Pascal, Laurent, MD</creatorcontrib><creatorcontrib>Fermé, Christophe, MD</creatorcontrib><creatorcontrib>Schiano, Jean-Marc, MD</creatorcontrib><creatorcontrib>Coiffier, Bertrand, Prof</creatorcontrib><creatorcontrib>Corront, Bernadette, MD</creatorcontrib><creatorcontrib>Farhat, Hassan, MD</creatorcontrib><creatorcontrib>Fruchart, Christophe, MD</creatorcontrib><creatorcontrib>Ghesquieres, Herve, Prof</creatorcontrib><creatorcontrib>Macro, Margaret, MD</creatorcontrib><creatorcontrib>Tilly, Hervé, Prof</creatorcontrib><creatorcontrib>Choufi, Bachra, MD</creatorcontrib><creatorcontrib>Delarue, Richard, MD</creatorcontrib><creatorcontrib>Fitoussi, Olivier, MD</creatorcontrib><creatorcontrib>Gabarre, Jean, MD</creatorcontrib><creatorcontrib>Haioun, Corinne, Prof</creatorcontrib><creatorcontrib>Jardin, Fabrice, Prof</creatorcontrib><title>Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group</title><title>The Lancet. Haematology</title><addtitle>Lancet Haematol</addtitle><description>Summary Background In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. Methods For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m2 of intravenous doxorubicin, 400 mg/m2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov , number NCT01195714. Findings Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions. Interpretation Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years. Funding The Lymphoma Study Association, GlaxoSmithKline.</description><subject>Aged, 80 and over</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic Agents, Immunological - administration & dosage</subject><subject>Antineoplastic Agents, Immunological - adverse effects</subject><subject>Antineoplastic Agents, Immunological - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Cyclophosphamide - adverse effects</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - adverse effects</subject><subject>Doxorubicin - therapeutic use</subject><subject>Female</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Lymphoma, Large B-Cell, Diffuse - drug therapy</subject><subject>Male</subject><subject>Prednisone - administration & dosage</subject><subject>Prednisone - adverse effects</subject><subject>Prednisone - therapeutic use</subject><subject>Sialic Acid Binding Ig-like Lectin 2 - antagonists & inhibitors</subject><subject>Treatment Outcome</subject><subject>Vincristine - administration & dosage</subject><subject>Vincristine - adverse effects</subject><subject>Vincristine - therapeutic use</subject><issn>2352-3026</issn><issn>2352-3026</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFqFDEUhgdRbKl9BOVcVtjRJDPJTr1Q6qJWKFSoXngVMsnJbmoymSYzwr6dj2Z2txbxRggkOfz_dzjnr6rnlLyihIrXN6zhrG4IE2dUvGwIXdKaP6qOH8qP_3ofVac53xJCaLMUXJw_rY5YR1rKu-a4-rWKoXeDmlwcINpy1DSHOage1GAgoZk1mtrEjLC6vP4CNiYwztq5FLxKa4T3tUbvwW_DuIlBZXADjAWIw5RBrdFAR2CLKmUo3ugNpjcFDnHEofaqR7-AMPvJ6eJIuIDshrXHWqWwgHGjSiMGU3LKg00xwLRBuPp-cwHrFOfxWfXEKp_x9P4-qb59_PB1dVlfXX_6vLq4qnXbialmXChqBbatMa3hlhikyBvWd6zrVc-X1naEtUQJ0netZcuOnAtKNV_u96abk-rswB1TvJsxTzK4vBtcDRjnLGnH2440gtMi5QepTjHnhFaOyQWVtpISuctP7vOTu3Bk-e3zk7z4Xty3mPuA5sH1J60ieHcQYBn0p8Mksy5rLgG5hHqSJrr_tnj7D0F7Nzit_A_cYr6NcxrKFiWVmUlygOwYVOwJvPkN2UC-9A</recordid><startdate>2017</startdate><enddate>2017</enddate><creator>Peyrade, Frédéric, Prof</creator><creator>Bologna, Serge, MD</creator><creator>Delwail, Vincent, MD</creator><creator>Emile, Jean François, Prof</creator><creator>Pascal, Laurent, MD</creator><creator>Fermé, Christophe, MD</creator><creator>Schiano, Jean-Marc, MD</creator><creator>Coiffier, Bertrand, Prof</creator><creator>Corront, Bernadette, MD</creator><creator>Farhat, Hassan, MD</creator><creator>Fruchart, Christophe, MD</creator><creator>Ghesquieres, Herve, Prof</creator><creator>Macro, Margaret, MD</creator><creator>Tilly, Hervé, Prof</creator><creator>Choufi, Bachra, MD</creator><creator>Delarue, Richard, MD</creator><creator>Fitoussi, Olivier, MD</creator><creator>Gabarre, Jean, MD</creator><creator>Haioun, Corinne, Prof</creator><creator>Jardin, Fabrice, Prof</creator><general>Elsevier Ltd</general><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>7X8</scope></search><sort><creationdate>2017</creationdate><title>Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group</title><author>Peyrade, Frédéric, Prof ; Bologna, Serge, MD ; Delwail, Vincent, MD ; Emile, Jean François, Prof ; Pascal, Laurent, MD ; Fermé, Christophe, MD ; Schiano, Jean-Marc, MD ; Coiffier, Bertrand, Prof ; Corront, Bernadette, MD ; Farhat, Hassan, MD ; Fruchart, Christophe, MD ; Ghesquieres, Herve, Prof ; Macro, Margaret, MD ; Tilly, Hervé, Prof ; Choufi, Bachra, MD ; Delarue, Richard, MD ; Fitoussi, Olivier, MD ; Gabarre, Jean, MD ; Haioun, Corinne, Prof ; Jardin, Fabrice, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-256a1f6e44dd4d5f0de1e532b828bab57ff80240a60b84f27809611c5700137c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged, 80 and over</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antineoplastic Agents, Immunological - administration & dosage</topic><topic>Antineoplastic Agents, Immunological - adverse effects</topic><topic>Antineoplastic Agents, Immunological - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Cyclophosphamide - adverse effects</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - adverse effects</topic><topic>Doxorubicin - therapeutic use</topic><topic>Female</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Lymphoma, Large B-Cell, Diffuse - drug therapy</topic><topic>Male</topic><topic>Prednisone - administration & dosage</topic><topic>Prednisone - adverse effects</topic><topic>Prednisone - therapeutic use</topic><topic>Sialic Acid Binding Ig-like Lectin 2 - antagonists & inhibitors</topic><topic>Treatment Outcome</topic><topic>Vincristine - administration & dosage</topic><topic>Vincristine - adverse effects</topic><topic>Vincristine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peyrade, Frédéric, Prof</creatorcontrib><creatorcontrib>Bologna, Serge, MD</creatorcontrib><creatorcontrib>Delwail, Vincent, MD</creatorcontrib><creatorcontrib>Emile, Jean François, Prof</creatorcontrib><creatorcontrib>Pascal, Laurent, MD</creatorcontrib><creatorcontrib>Fermé, Christophe, MD</creatorcontrib><creatorcontrib>Schiano, Jean-Marc, MD</creatorcontrib><creatorcontrib>Coiffier, Bertrand, Prof</creatorcontrib><creatorcontrib>Corront, Bernadette, MD</creatorcontrib><creatorcontrib>Farhat, Hassan, MD</creatorcontrib><creatorcontrib>Fruchart, Christophe, MD</creatorcontrib><creatorcontrib>Ghesquieres, Herve, Prof</creatorcontrib><creatorcontrib>Macro, Margaret, MD</creatorcontrib><creatorcontrib>Tilly, Hervé, Prof</creatorcontrib><creatorcontrib>Choufi, Bachra, MD</creatorcontrib><creatorcontrib>Delarue, Richard, MD</creatorcontrib><creatorcontrib>Fitoussi, Olivier, MD</creatorcontrib><creatorcontrib>Gabarre, Jean, MD</creatorcontrib><creatorcontrib>Haioun, Corinne, Prof</creatorcontrib><creatorcontrib>Jardin, Fabrice, Prof</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet. Haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peyrade, Frédéric, Prof</au><au>Bologna, Serge, MD</au><au>Delwail, Vincent, MD</au><au>Emile, Jean François, Prof</au><au>Pascal, Laurent, MD</au><au>Fermé, Christophe, MD</au><au>Schiano, Jean-Marc, MD</au><au>Coiffier, Bertrand, Prof</au><au>Corront, Bernadette, MD</au><au>Farhat, Hassan, MD</au><au>Fruchart, Christophe, MD</au><au>Ghesquieres, Herve, Prof</au><au>Macro, Margaret, MD</au><au>Tilly, Hervé, Prof</au><au>Choufi, Bachra, MD</au><au>Delarue, Richard, MD</au><au>Fitoussi, Olivier, MD</au><au>Gabarre, Jean, MD</au><au>Haioun, Corinne, Prof</au><au>Jardin, Fabrice, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group</atitle><jtitle>The Lancet. Haematology</jtitle><addtitle>Lancet Haematol</addtitle><date>2017</date><risdate>2017</risdate><volume>4</volume><issue>1</issue><spage>e46</spage><epage>e55</epage><pages>e46-e55</pages><issn>2352-3026</issn><eissn>2352-3026</eissn><abstract>Summary Background In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49–67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. Methods For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day −7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day −7 to day −4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m2 of intravenous doxorubicin, 400 mg/m2 of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m2 of oral prednisone on days 1–5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov , number NCT01195714. Findings Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2–3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5–30·1). The 2-year overall survival was 64·7% (95% CI 55·3–72·7) and median overall survival was not reached (95% CI 30·2–not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3–4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3–4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions. Interpretation Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years. Funding The Lymphoma Study Association, GlaxoSmithKline.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28041583</pmid><doi>10.1016/S2352-3026(16)30171-5</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2352-3026 |
| ispartof | The Lancet. Haematology, 2017, Vol.4 (1), p.e46-e55 |
| issn | 2352-3026 2352-3026 |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Aged, 80 and over Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Antineoplastic Agents, Immunological - administration & dosage Antineoplastic Agents, Immunological - adverse effects Antineoplastic Agents, Immunological - therapeutic use Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cyclophosphamide - administration & dosage Cyclophosphamide - adverse effects Cyclophosphamide - therapeutic use Doxorubicin - administration & dosage Doxorubicin - adverse effects Doxorubicin - therapeutic use Female Hematology, Oncology and Palliative Medicine Humans Lymphoma, Large B-Cell, Diffuse - drug therapy Male Prednisone - administration & dosage Prednisone - adverse effects Prednisone - therapeutic use Sialic Acid Binding Ig-like Lectin 2 - antagonists & inhibitors Treatment Outcome Vincristine - administration & dosage Vincristine - adverse effects Vincristine - therapeutic use |
| title | Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group |
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