Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study

Background: Epigenetic priming prior to chemotherapy represents a promising treatment strategy for refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL). We conducted a phase II trial to evaluate the efficacy and safety of azacitidine in combination with R-GDP (rituximab/gemcitabine/dexam...

Full description

Saved in:
Bibliographic Details
Main Authors: Dong Hyun Kim, Jee Hyun Kong, Junshik Hong, Ja Min Byun, Dong-Yeop Shin, Youngil Koh, Inho Kim, Jinny Park, Young Rok Do, Jeong-A Kim, Won Seog Kim, Ho-Jin Shin, Sung-Soo Yoon
Format: Article
Language:English
Published: SAGE Publishing 2025-07-01
Series:Therapeutic Advances in Hematology
Online Access:https://doi.org/10.1177/20406207251349361
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849427661439369216
author Dong Hyun Kim
Jee Hyun Kong
Junshik Hong
Ja Min Byun
Dong-Yeop Shin
Youngil Koh
Inho Kim
Jinny Park
Young Rok Do
Jeong-A Kim
Won Seog Kim
Ho-Jin Shin
Sung-Soo Yoon
author_facet Dong Hyun Kim
Jee Hyun Kong
Junshik Hong
Ja Min Byun
Dong-Yeop Shin
Youngil Koh
Inho Kim
Jinny Park
Young Rok Do
Jeong-A Kim
Won Seog Kim
Ho-Jin Shin
Sung-Soo Yoon
author_sort Dong Hyun Kim
collection DOAJ
description Background: Epigenetic priming prior to chemotherapy represents a promising treatment strategy for refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL). We conducted a phase II trial to evaluate the efficacy and safety of azacitidine in combination with R-GDP (rituximab/gemcitabine/dexamethasone/cisplatin) in transplant-ineligible R/R DLBCL. Methods: Fifteen patients were enrolled and treated with azacitidine and R-GDP regimen (NCT03719989). Azacitidine was administered intravenously at a dose of 25 mg/m 2 /day for 5 days. Each cycle consisted of 21 days, with patients receiving up to a maximum of six cycles. The primary endpoint was the objective response rate, and the secondary objectives were toxicity, progression-free survival (PFS), and overall survival (OS). Results: Overall, 15 patients were enrolled in the study from March 2019 to August 2023, and the median age was 64 years (range: 41–75). The objective response rate was 66.7% with a complete response rate of 53.3%. The most common grade 3 or higher adverse events were hematologic toxicities, including neutropenia (66.7%) and thrombocytopenia (53.3%). Grade 3 or higher non-hematologic toxicities were rare, and most adverse events were transient and manageable. During a median follow-up of 15.8 months, five patients died, all from DLBCL. The median PFS was 12.6 months, while the median OS was not reached. Conclusion: Our study suggests that azacitidine followed by R-GDP is an effective and safe strategy for transplant-ineligible patients with R/R DLBCL. This represents the first phase II study to demonstrate the potential of epigenetic priming with azacitidine to enhance chemosensitivity in this patient population. Trial registration: ClinicalTrials.gov identifier: NCT03719989.
format Article
id doaj-art-7ef96f920aeb4fadad6f22f46ac7c818
institution Kabale University
issn 2040-6215
language English
publishDate 2025-07-01
publisher SAGE Publishing
record_format Article
series Therapeutic Advances in Hematology
spelling doaj-art-7ef96f920aeb4fadad6f22f46ac7c8182025-08-20T03:28:58ZengSAGE PublishingTherapeutic Advances in Hematology2040-62152025-07-011610.1177/20406207251349361Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II studyDong Hyun KimJee Hyun KongJunshik HongJa Min ByunDong-Yeop ShinYoungil KohInho KimJinny ParkYoung Rok DoJeong-A KimWon Seog KimHo-Jin ShinSung-Soo YoonBackground: Epigenetic priming prior to chemotherapy represents a promising treatment strategy for refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL). We conducted a phase II trial to evaluate the efficacy and safety of azacitidine in combination with R-GDP (rituximab/gemcitabine/dexamethasone/cisplatin) in transplant-ineligible R/R DLBCL. Methods: Fifteen patients were enrolled and treated with azacitidine and R-GDP regimen (NCT03719989). Azacitidine was administered intravenously at a dose of 25 mg/m 2 /day for 5 days. Each cycle consisted of 21 days, with patients receiving up to a maximum of six cycles. The primary endpoint was the objective response rate, and the secondary objectives were toxicity, progression-free survival (PFS), and overall survival (OS). Results: Overall, 15 patients were enrolled in the study from March 2019 to August 2023, and the median age was 64 years (range: 41–75). The objective response rate was 66.7% with a complete response rate of 53.3%. The most common grade 3 or higher adverse events were hematologic toxicities, including neutropenia (66.7%) and thrombocytopenia (53.3%). Grade 3 or higher non-hematologic toxicities were rare, and most adverse events were transient and manageable. During a median follow-up of 15.8 months, five patients died, all from DLBCL. The median PFS was 12.6 months, while the median OS was not reached. Conclusion: Our study suggests that azacitidine followed by R-GDP is an effective and safe strategy for transplant-ineligible patients with R/R DLBCL. This represents the first phase II study to demonstrate the potential of epigenetic priming with azacitidine to enhance chemosensitivity in this patient population. Trial registration: ClinicalTrials.gov identifier: NCT03719989.https://doi.org/10.1177/20406207251349361
spellingShingle Dong Hyun Kim
Jee Hyun Kong
Junshik Hong
Ja Min Byun
Dong-Yeop Shin
Youngil Koh
Inho Kim
Jinny Park
Young Rok Do
Jeong-A Kim
Won Seog Kim
Ho-Jin Shin
Sung-Soo Yoon
Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study
Therapeutic Advances in Hematology
title Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study
title_full Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study
title_fullStr Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study
title_full_unstemmed Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study
title_short Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study
title_sort azacitidine followed by r gdp in transplant ineligible relapsed refractory diffuse large b cell lymphoma preliminary results from a multicenter phase ii study
url https://doi.org/10.1177/20406207251349361
work_keys_str_mv AT donghyunkim azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT jeehyunkong azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT junshikhong azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT jaminbyun azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT dongyeopshin azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT youngilkoh azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT inhokim azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT jinnypark azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT youngrokdo azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT jeongakim azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT wonseogkim azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT hojinshin azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy
AT sungsooyoon azacitidinefollowedbyrgdpintransplantineligiblerelapsedrefractorydiffuselargebcelllymphomapreliminaryresultsfromamulticenterphaseiistudy