Nivolumab discontinuation and retreatment in patients with relapsed or refractory Hodgkin lymphoma

Fedorova, L.; Lepik, Kirill V.; Mikhailova, N.; Kondakova, Elena; Zalyalov, Y.; Baykov, Vadim; Babenko, Elena V.; Kozlov, Andrey V.; Moiseev, Ivan S.; Afanasyev, Boris

doi:10.1007/s00277-021-04429-8

Cited by 13 publications

(14 citation statements)

References 29 publications

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“… 41 On the other hand, recent innovations including sequencing technology, gene modification and big data analytics have significantly impacted on selecting treatment strategies. 42 For instance, molecular targeted drugs, 43 chimeric antigen receptor T‐cell therapy 44 and immune checkpoint inhibitors 45 have the potential to replace HSCT as the standard curative therapy for haematopoietic malignancies in the near future. These changes in clinical practise indicate the need to reconsider the use of HSCT in various situations.…”

Section: Discussionmentioning

confidence: 99%

Identification of the minimum requirements for successful haematopoietic stem cell transplantation

et al. 2021

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Historically, defining haematopoietic subsets, including self-renewal, differentiation and lineage restriction, has been elucidated by transplanting a small number of candidate cells with many supporting bone marrow (BM) cells. While this approach has been invaluable in characterising numerous distinct subsets in haematopoiesis, this approach is arguably flawed. The haematopoietic stem cell (HSC) has been proposed as the critical haematopoietic subset necessary for transplantation. However, due to the presence of supporting cells, the HSC has never demonstrated sufficiency. Utilising the homeobox B5 (Hoxb5)-reporter system, we found that neither long-term (LT) HSCs nor short-term (ST) HSCs alone were sufficient for long-term haematopoietic reconstitution. Critically, reconstitution can be rescued by transplanting combined LT-and ST-HSCs, without supporting cells; a fraction we term the 'Minimum Subset for Transplantation' (MST). The MST accounts for only 0Á005% of nucleated cells within mouse BM, and this MST can be cultured, expanded and genetically modified while preserving its rapid haematopoietic engraftment potential. These results support the consideration of an MST approach for clinical translation, especially for gene therapy approaches that require HSC compartment modification.

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Section: Discussionmentioning

confidence: 99%

Identification of the minimum requirements for successful haematopoietic stem cell transplantation

et al. 2021

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“…In a small single institution study of 23 patients who discontinued nivolumab in CR, 11 relapsed and 9 were re-treated with single agent nivolumab. Three achieved a CR, 3 a PR and 3 an indeterminate response [ 30 ]. There is clear efficacy therefore in re-treating patients with PD1 inhibitor if stopped due to a CR.…”

Section: Moving Cpi Therapy Into the Pre-asct Settingmentioning

confidence: 99%

Checkpoint Inhibitors and the Changing Face of the Relapsed/Refractory Classical Hodgkin Lymphoma Pathway

Zhang

Collins

2022

Curr Oncol Rep

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Purpose of Review Checkpoint inhibitors (CPIs) targeting PD1 are highly active in relapsed/refractory classical Hodgkin lymphoma. A plethora of recent studies, often small and non-randomised, have raised many questions about how to optimally integrate these into clinical practice. We aim to discuss the use of CPIs in different relapsed/refractory settings in an effort to better define their role and highlight areas of research. Recent Findings CPIs have shown efficacy at first relapse, as salvage pre- and post-autologous (ASCT) and allogeneic stem cell transplant (alloSCT) and as maintenance post-ASCT. Immune-related adverse events require careful attention, especially when used peri-alloSCT, where it is associated with hyperacute graft-versus-host disease. Newer PD1 inhibitors, as well as strategies to overcome CPI resistance, are being tested. Summary CPIs are increasingly deployed at earlier points in the classical Hodgkin lymphoma pathway. Whilst progress is clearly being made, randomised studies are required to more clearly define the optimal positioning of these agents.

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“…Another retrospective study presented that 11 (48%) patients relapsed after treatment discontinuation among the 23 patients with relapsed/refractory cHL who acquired CR following nivolumab therapy, and nine patients relapsed within 18 months since treatment cessation. 23 Our study included 57 patients who discontinued decitabine-plus-camrelizumab therapy, the largest number of sample size ever published, nearly 80% of patients therein remained remission after a median follow-up of 3 years since treatment cessation. Therefore, decitabine-plus-camrelizumab therapy might be a potentially curative approach in a proportion of cHL patients, especially on 3-4-week consolidation protocol, rather than only as a bridge to transplantation.…”

Section: Discussionmentioning

confidence: 99%

Long‐term complete remission and peripheral biomarkers in Hodgkin lymphoma patients after decitabine‐plus‐camrelizumab epi‐immunotherapy and treatment cessation

Wang,

Pan,

Liu

et al. 2023

MedComm

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Patients with relapsed/refractory classical Hodgkin lymphoma (cHL) achieve complete response (CR) after decitabine‐plus‐camrelizumab therapy, while long‐term outcome especially after treatment discontinuation remains unclear. We present a retrospective analysis of 87 relapsed/refractory cHL patients who acquired CR after decitabine‐plus‐camrelizumab. Patients were divided into two groups and received consolidation treatment every 3–4 or 6–12 weeks, and 1‐year of continuous CR was guaranteed for treatment cessation. At a median follow‐up of 5.3 years, the median relapse‐free survival (RFS) after achieving CR with decitabine‐plus‐camrelizumab therapy was 4.5 years, and patients underwent consolidation per 3–4 weeks might have longer RFS. The baseline percentage of peripheral central memory T cells was not associated with RFS, while patients with higher pretreatment serum levels of interleukin‐6 (IL‐6) and lactate dehydrogenase (LDH) had significantly shorter RFS and increased risk for disease recurrence. Fifty‐seven patients completed and discontinued decitabine‐plus‐camrelizumab, and their median RFS had not been reached. The 2‐year RFS rate after treatment cessation was 78% (95% CI, 67–90%). Patients in the high‐risk subgroup with higher pretreatment IL‐6 and LDH levels showed poor treatment‐free remission. Moreover, decitabine‐plus‐camrelizumab therapy was safe and cost‐effective. In conclusion, patients who obtained CR with decitabine‐plus‐camrelizumab and received consolidation per 3–4 weeks can achieve long‐term remission after treatment discontinuation.

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Nivolumab discontinuation and retreatment in patients with relapsed or refractory Hodgkin lymphoma

Cited by 13 publications

References 29 publications

Identification of the minimum requirements for successful haematopoietic stem cell transplantation

Identification of the minimum requirements for successful haematopoietic stem cell transplantation

Checkpoint Inhibitors and the Changing Face of the Relapsed/Refractory Classical Hodgkin Lymphoma Pathway

Long‐term complete remission and peripheral biomarkers in Hodgkin lymphoma patients after decitabine‐plus‐camrelizumab epi‐immunotherapy and treatment cessation

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