Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases

<b>Background/Objectives</b><i>:</i> Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambuc...

Full description

Saved in:
Bibliographic Details
Main Authors: Igor Aurer, Ozren Jakšić, Sandra Bašić-Kinda, Karla Mišura-Jakobac, Jasminka Sinčić-Petričević, Sabina Novaković-Coha, Davor Galušić, Hrvoje Holik, Toni Valković, Dubravka Županić-Krmek, Ida Hude-Dragičević, Vibor Milunović, Vlatko Pejša
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/12/12/2902
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850240166923337728
author Igor Aurer
Ozren Jakšić
Sandra Bašić-Kinda
Karla Mišura-Jakobac
Jasminka Sinčić-Petričević
Sabina Novaković-Coha
Davor Galušić
Hrvoje Holik
Toni Valković
Dubravka Županić-Krmek
Ida Hude-Dragičević
Vibor Milunović
Vlatko Pejša
author_facet Igor Aurer
Ozren Jakšić
Sandra Bašić-Kinda
Karla Mišura-Jakobac
Jasminka Sinčić-Petričević
Sabina Novaković-Coha
Davor Galušić
Hrvoje Holik
Toni Valković
Dubravka Županić-Krmek
Ida Hude-Dragičević
Vibor Milunović
Vlatko Pejša
author_sort Igor Aurer
collection DOAJ
description <b>Background/Objectives</b><i>:</i> Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. <b>Methods:</b> This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. <b>Results:</b> Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (<i>p</i> = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. <b>Conclusions:</b> The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.
format Article
id doaj-art-d8d2366cd134447bb4f0a91302698c4e
institution OA Journals
issn 2227-9059
language English
publishDate 2024-12-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj-art-d8d2366cd134447bb4f0a91302698c4e2025-08-20T02:00:55ZengMDPI AGBiomedicines2227-90592024-12-011212290210.3390/biomedicines12122902Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic DiseasesIgor Aurer0Ozren Jakšić1Sandra Bašić-Kinda2Karla Mišura-Jakobac3Jasminka Sinčić-Petričević4Sabina Novaković-Coha5Davor Galušić6Hrvoje Holik7Toni Valković8Dubravka Županić-Krmek9Ida Hude-Dragičević10Vibor Milunović11Vlatko Pejša12Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb and Medical School, University of Zagreb, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Dubrava and Medical School, University of Zagreb, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Centre Osijek, 31000 Osijek, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Centre Sisters of Mercy, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, Division of Haematology, University Hospital Centre Split, 21000 Split, CroatiaHematology-Oncology Unit, Internal Medicine Service, General Hospital Dr. Josip Benčević, 35000 Slavonski Brod, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Centre Rijeka and Medical School, University of Rijeka, 51000 Rijeka, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Holy Spirit, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Merkur, 10000 Zagreb, CroatiaDivision of Hematology, Department of Internal Medicine, University Hospital Dubrava and Medical School, University of Zagreb, 10000 Zagreb, Croatia<b>Background/Objectives</b><i>:</i> Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. <b>Methods:</b> This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. <b>Results:</b> Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (<i>p</i> = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. <b>Conclusions:</b> The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.https://www.mdpi.com/2227-9059/12/12/2902chronic lymphocytic leukemiaobinutuzumabchlorambucil
spellingShingle Igor Aurer
Ozren Jakšić
Sandra Bašić-Kinda
Karla Mišura-Jakobac
Jasminka Sinčić-Petričević
Sabina Novaković-Coha
Davor Galušić
Hrvoje Holik
Toni Valković
Dubravka Županić-Krmek
Ida Hude-Dragičević
Vibor Milunović
Vlatko Pejša
Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases
Biomedicines
chronic lymphocytic leukemia
obinutuzumab
chlorambucil
title Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases
title_full Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases
title_fullStr Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases
title_full_unstemmed Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases
title_short Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases
title_sort obinutuzumab in combination with alternative chlorambucil schedules in front line treatment of chronic lymphocytic leukemia a study by krohem the croatian cooperative group for hematologic diseases
topic chronic lymphocytic leukemia
obinutuzumab
chlorambucil
url https://www.mdpi.com/2227-9059/12/12/2902
work_keys_str_mv AT igoraurer obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT ozrenjaksic obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT sandrabasickinda obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT karlamisurajakobac obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT jasminkasincicpetricevic obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT sabinanovakoviccoha obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT davorgalusic obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT hrvojeholik obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT tonivalkovic obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT dubravkazupanickrmek obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT idahudedragicevic obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT vibormilunovic obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases
AT vlatkopejsa obinutuzumabincombinationwithalternativechlorambucilschedulesinfrontlinetreatmentofchroniclymphocyticleukemiaastudybykrohemthecroatiancooperativegroupforhematologicdiseases