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Original Article

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Blood Res 2021; 56(3):

Published online September 30, 2021

https://doi.org/10.5045/br.2021.2021039

© The Korean Society of Hematology

Bendamustine in combination with ifosfamide, etoposide, and vinorelbine (VIBE) is an effective salvage regimen for heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma: a single-center experience

Gaurav Prakash1, Arihant Jain1, Kamalkant Sahu1, Amanjit Bal2, Charanpreet Singh1, Rajender Basher3, Harmandeep Singh3, Kundan Mishra1, Aditya Jandial1, Deepesh Lad1, Alka Khadwal1, Radhika Srinivasan4, Ashim Das2, Neelam Varma5, Subhash Varma1, Pankaj Malhotra1

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1Clinical Hematology and BMT Division, Department of Internal Medicine, 2Department of Nuclear Medicine, 3Department of Histopathology, 4Department of Cytopathology, 5Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence to : Pankaj Malhotra, M.D.
Clinical Hematology and BMT Division, Department of Internal Medicine, Nehru Hospital, Postgraduate Institute of Medical Education and Research, F block, 4th floor, Chandigarh 160012, India
E-mail: malhotrapankaj@hotmail.com

Received: February 23, 2021; Revised: June 7, 2021; Accepted: July 8, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background
This study evaluated the outcomes of patients with refractory/relapsed Hodgkin lymphoma (RRHL) treated with a bendamustine-based regimen in combination with ifosfamide, etoposide, and vinorelbine (VIBE).
Methods
Consecutive RRHL patients who were treated with the VIBE regimen were identified and studied for clinicopathologic characteristics, response to VIBE regimen, event-free survival (EFS), and feasibility of an autologous stem-cell transplant (autoSCT).
Results
In total, 24 patients received the VIBE regimen, and a median of 3 cycles were administered. In this cohort, 80% of the patients had received ≥2 prior lines of therapy. The overall and complete response rates with VIBE were 79% and 42%, respectively. After a median follow-up (following VIBE regimen) of 14 months (range, 3‒76), the 3-year EFS and OS were 46% and 74%, respectively. Of the eligible patients, 92% underwent successful AutoSCT. The mean CD34+ cell count in the autograft was 5.5×106/kg (SD 2.07). Neutropenia was the commonest hematologic toxicity and it was observed in 42% of the patients. However, only 9% of the patients developed grade III/IV febrile neutropenia. Chemotherapy-induced nausea and vomiting were the second most common grade III/IV toxicities in our cohort of patients.
Conclusion
In this retrospective analysis, the combination regimen, VIBE, has shown good efficacy in heavily pre-treated patients with RRHL without compromising stem cell collection. These encouraging results provide a rationale for further development of this regimen.

Keywords Relapsed refractory, Hodgkin Lymphoma, Salvage, Bendamustine, Autologous transplant

Article

Original Article

Blood Res 2021; 56(3): 134-140

Published online September 30, 2021 https://doi.org/10.5045/br.2021.2021039

Copyright © The Korean Society of Hematology.

Bendamustine in combination with ifosfamide, etoposide, and vinorelbine (VIBE) is an effective salvage regimen for heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma: a single-center experience

Gaurav Prakash1, Arihant Jain1, Kamalkant Sahu1, Amanjit Bal2, Charanpreet Singh1, Rajender Basher3, Harmandeep Singh3, Kundan Mishra1, Aditya Jandial1, Deepesh Lad1, Alka Khadwal1, Radhika Srinivasan4, Ashim Das2, Neelam Varma5, Subhash Varma1, Pankaj Malhotra1

1Clinical Hematology and BMT Division, Department of Internal Medicine, 2Department of Nuclear Medicine, 3Department of Histopathology, 4Department of Cytopathology, 5Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence to:Pankaj Malhotra, M.D.
Clinical Hematology and BMT Division, Department of Internal Medicine, Nehru Hospital, Postgraduate Institute of Medical Education and Research, F block, 4th floor, Chandigarh 160012, India
E-mail: malhotrapankaj@hotmail.com

Received: February 23, 2021; Revised: June 7, 2021; Accepted: July 8, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
This study evaluated the outcomes of patients with refractory/relapsed Hodgkin lymphoma (RRHL) treated with a bendamustine-based regimen in combination with ifosfamide, etoposide, and vinorelbine (VIBE).
Methods
Consecutive RRHL patients who were treated with the VIBE regimen were identified and studied for clinicopathologic characteristics, response to VIBE regimen, event-free survival (EFS), and feasibility of an autologous stem-cell transplant (autoSCT).
Results
In total, 24 patients received the VIBE regimen, and a median of 3 cycles were administered. In this cohort, 80% of the patients had received ≥2 prior lines of therapy. The overall and complete response rates with VIBE were 79% and 42%, respectively. After a median follow-up (following VIBE regimen) of 14 months (range, 3‒76), the 3-year EFS and OS were 46% and 74%, respectively. Of the eligible patients, 92% underwent successful AutoSCT. The mean CD34+ cell count in the autograft was 5.5×106/kg (SD 2.07). Neutropenia was the commonest hematologic toxicity and it was observed in 42% of the patients. However, only 9% of the patients developed grade III/IV febrile neutropenia. Chemotherapy-induced nausea and vomiting were the second most common grade III/IV toxicities in our cohort of patients.
Conclusion
In this retrospective analysis, the combination regimen, VIBE, has shown good efficacy in heavily pre-treated patients with RRHL without compromising stem cell collection. These encouraging results provide a rationale for further development of this regimen.

Keywords: Relapsed refractory, Hodgkin Lymphoma, Salvage, Bendamustine, Autologous transplant

Fig 1.

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Figure 1.Y-axis: CR/CRu rates (expressed in percentage); X-axis: various variables.
Blood Research 2021; 56: 134-140https://doi.org/10.5045/br.2021.2021039

Fig 2.

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Figure 2.Kaplan-Meier survival curve for event-free survival (A). Whole group. EFS according to response to VIBE therapy (B). EFS according to age group (C). EFS according to AutoHSCT status (D).
Blood Research 2021; 56: 134-140https://doi.org/10.5045/br.2021.2021039

Table 1 . Patient characteristics and disease-related variables..

ParametersN (%)
Age, years, median (range)25 (13–60)
Gender ratioM:F=3:1
B-symptoms13 (54)
Bulky disease5 (20.8)
Extranodal disease5 (20.8)
cHL subtypes
Nodular sclerosis13 (54)
Mixed cellularity4 (16.6)
Unclassified7 (33.3)
Previous 2 lines failed19 (80)
Stage at the time of starting VIBE stage
Stage II6 (25)
Stage III10 (41.6)
Stage IV8 (33.3)
Numbers of VIBE regimen received
Two courses9 (37.5)
Three courses6 (25)
Four courses9 (37.5)

Abbreviations: cHL, classical Hodgkin lymphoma; VIBE, vinorelbine, ifosfamide, bendamustine, etoposide..

Table 2 . Characteristics of individual patients..

No.Age/
sex		Stage at the time of diagnosisPrior regimen usedPrevious N of therapyDiagnosis to VIBE (mo)Stage before VIBEVIBE cyclesResponse after VIBEAuto HSCT
yes/no
Relapsed cases of cHL
121/FII-AABVD×6 (2012)-CR, IFRT 30Gy, GDP×4 (2013)-PD322III2CRYes
228/MII-BABVD×6 (2014)-CR, GDP×3 (2016)-PR231III2CRUYes
313/MII-AABVD×6 (2013)-CR, GDP×4 (2016)-SD254III2CRUYes
425/MII-AXABVD×6 (2014)-CR, Bendamustine×2, RT (PR)
GDP×2-PR, Nivolumab×8 doses-PR but soon progressed		241III2PDNo
515/MII-BABVD×6 (2010)-CR, IEV×4 RT to mediastinum (2012)-CR, GDP×2 (2019)-SD490III3
CRYes
613/MIII-BABVD×6 (2016)-CR
GDP×2 (2019)-PD		244III3CRUNo
729/MIII-BSABVD×6 (2016)-CR148III4CRUYes
Primary refractory cases of cHL
821/MIII-BEXABVD×4 (2013)-PR, BEACOPP×3 (2013)-PR, IFRT 30 Gy, GDP× (2014)-PR420I2CRYes
920/MIII-BCOPP×1
BEACOPP×5,-PD		26III2PDNo
1060/MIV -BSABVD×6 (2016)-PD, Splenectomy216IV4CRNo
1127/MIV-AECHV+Bleomycin, Etoposide×6 (2014)-PR
DHAP×2 (2014)-PD, ICE×4 (2015)-SD		327IV4CRYes
1226/MIV-BEABVD×6 (2016)-PD18IV3CRUYes
1333/MIV AEXABVD×4 (2015)-SD,
GDP×4 (2016)-PD		220IV4CRUYes
1427/MII-AABVD×4 (2017)-PD15III4CRYes
1518/MIII BXABVD×4 (2015)-SD15III3CRNo
1627/FII-BXABVD×6 (2017) PR, GDP×2 (2018)-PR, IFRT-PD313I4PRNo
1721/FIV-BABVD×6 (2018) PR, GDP×2 (2019)-PR212IV3CRUNo
1821/MIII-BABVD×6 (2018) PD, GDP×4 (2019)-PD210III3CRYes
1926/MIVBABVD×5 (2018)-SD
GDP×2 (2019)-PR		224IV4PDNo
2025/MIVBECOPP×1
ABVD×5 (2019)-PD
GDP×2 (2019)-PD		215IV2SDNo
2114/FIVACOPP×2 (2019)-PR
ABVD×6 (2020)-PD		213II3CRYes
2228/FIVBSABVD×6 (2019)-PR125IV4PDNo
2322/fII-BABVD×6 (2018)-PD, GDP×2 (2019)-SD219IV2CRUNo
2425/mIII-AABVD×6 (2012-13)-PD
COPP×6 (2013)-PD
IFRT 10 Fr (2015), CEP×3 (2016)-PR		460III2CRNo

Abbreviations: ABVD, adriamycin, bleomycin, vinblastine, dacarbazine; BEACOPP, bleomycin, etoposide, cytarabine, cyclophosphamide, oncovin, procarbazine, prednisolone; COPP, cyclophosphamide, oncovin, procarbazine, prednisolone; CR, complete remission; CRU, complete remission unconfirmed; DHAP, dexamethasone, cytarabine, cisplatin; GDP, Gemcitabine, dexamethasone, cisplatin; ICE, ifosfamide, carboplatin, etoposide; IFRT, involved field radiotherapy; PD, progressive disease; PR, partial remission; SD, stable disease..

Table 3 . Comparison of various salvage regimens for relapsed or refractory Hodgkin lymphoma..

RegimenMedian lines failedCR (%)ORR (%)Successful stem cell mobilisation (%)PFS
ICE [15]126889658% at 3.5 yr
GDP [6]110629774% at 18 mo
miniBEAM [6]120685735% at 18 mo
IGEV [11]1548198NR
BeGEV [12]173839662% 2 yr
BV [8]3.53475NR22% at 5 yr
BV+nivolumab [9]16285NRNR
VIBE current study342799261% 2 yr, EFS

Abbreviations: BeGEV, bendamustine, gemcitabine, and vinorelbine; BV, brentuximab vedoin; CR, complete remission; EFS, event free survival; GDP, gemcitabine, dexamethasone, cisplatin; ICE, ifosfamide, carboplatin, etoposide; IGEV, ifosfamide, gemcitabine, etoposide, and vinorelbine; miniBEAM, carmustine, etoposide, cytarabine, melphalan; NR, not reported; ORR, overall response rate; PFS, progression free survival..
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