Nivolumab before and after allogeneic hematopoietic cell transplantation

Covut, Fahrettin; Pinto, Raisa; Cooper, Brenda; Tomlinson, Ben; Metheny, Leland; Malek, Ehsan; Lazarus, Hillard M.; Lima, Marcos de; Caimi, Paolo

doi:10.1038/bmt.2017.44

Cited by 15 publications

(11 citation statements)

References 14 publications

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“…Twelve patients (46%) were treated with pembrolizumab (PD-1 blockade), three with a dose of 2.0 mg/kg every 3 weeks and two with a single dose therapy (3.3 mg/kg; not mentioned). The other fourteen patients (54%) were treated with nivolumab (PD-1 blockade), two with a single infusion at 3 mg/kg (27), two patients with six and four cycles (dose not mentioned) respectively (26). Two patients received a single dose of 100 mg (25) and 200 mg (24), two were treated with a single 3 mg/kg dose, one with two doses of 100 mg (25) two weeks apart, two cases with thirteen (23) and sixteen (20) cycles of 3 mg/kg every two weeks, one case with seven cycles of 2 mg/kg every two weeks (16), two cases with seven (19) and sixteen cycles (16) of 2 mg/kg every three weeks respectively.…”

Section: Resultsmentioning

confidence: 99%

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

Ijaz

Khan

Malik

et al. 2019

Biology of Blood and Marrow Transplantation

148

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Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further.

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Section: Resultsmentioning

confidence: 99%

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

Ijaz

Khan

Malik

et al. 2019

Biology of Blood and Marrow Transplantation

148

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“…A total of 272 records were screened (Figure ). In the investigational cohort (cohort 1), eight publications with a total of 155 patients underwent special analysis. Although two studies with the same first author were reporting on different patient numbers and outcomes, only one of these studies was included.…”

Section: Resultsmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint inhibitors: Feasibility and safety

Dada

Usman

2018

European J of Haematology

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Objectives Relapsed cHL patients after autologous hematopoietic stem cell transplantation (HSCT) with treatment‐sensitive disease are potential candidates for curative allogeneic HSCT. However, there are some concerns around performing such procedure after checkpoint inhibitors (CPIs). Methods We collected published data of patients undergoing allogeneic HSCT after treatment with CPIs (cohort 1). Abstracts of recent conferences (2015‐2017; ASCO, ASH, EBMT, ASBMT) were also included. Results were compared with safety of recent studies (2015‐2018) with allogeneic HSCT without CPIs (cohort 2). Results A total of 272 records were screened. After exclusion of duplications, cohorts 1 and 2 included each 6 publications with 122 and 978 patients, respectively. Grade 3‐4 acute GVHD in cohort 1 was found in 28% vs 8% in cohort 2 (P = 0.02). Chronic GVHD was observed in 26% vs 29%, respectively. NRM was 15% which remained relatively stable after 6 months of allogeneic HSCT vs 19% in cohort 2. Conclusions This is the largest pooled analysis of its kind published so far. Our results suggest that allogeneic HSCT after CPIs is feasible and not associated with higher mortality. However, careful consideration should be given for prevention, early detection, and effective treatment of GVHD in these cases. Additional prospective studies are needed for further clarification.

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Section: Introductionmentioning

confidence: 99%

“…There was a case report where nivolumab was used in five patients with Hodgkin lymphoma 24. Two patients on disease relapse after allogenic-haematopoietic stem cell transplantation were treated with nivolumab and one of them had a good clinical response and none of them developed graft versus host disease 24. Remaining three patients were given nivolumab before allogenic-HSCT (Hematopoietic stem cell transplantation) and two of them had a good disease response and GVHD (Graft versus has occurred in only one of the three patients 24.…”

Section: Introductionmentioning

confidence: 99%

“…Two patients on disease relapse after allogenic-haematopoietic stem cell transplantation were treated with nivolumab and one of them had a good clinical response and none of them developed graft versus host disease 24. Remaining three patients were given nivolumab before allogenic-HSCT (Hematopoietic stem cell transplantation) and two of them had a good disease response and GVHD (Graft versus has occurred in only one of the three patients 24. Another case report has demonstrated successful tumour clinical response in a patient with Hodgkin lymphoma after using nivolumab postallogenic-HSCT without the risk of GVHD 25.…”

Section: Introductionmentioning

confidence: 99%

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Immune checkpoint inhibitors in the management of malignancies in transplant recipients

Regalla

Williams

Paluri

2018

Postgraduate Medical Journal

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Cancer immunotherapy, an area of active research, has thus far yielded several exciting breakthroughs in cancer treatment strategies. So far, immune checkpoint inhibitors have been the most promising method of cancer immunotherapy. CTLA-4, PD-1 and PD-L1 are the immune checkpoint molecules against which monoclonal antibodies act against and revolutionised the treatment of several malignancies. However, it is still unclear whether using these monoclonal antibodies in patients with malignancy and a history of transplant is as beneficial as in patients without a history of transplantation. The reason being, with the therapeutic benefit, also comes the inherent disadvantage of transplant rejection because of the activation of T-cells against donor antigens. So, transplant-related complications limit the usage of the checkpoint blockade therapy to treat malignancies. Here, we review the data published in this context and suggest optimal approaches to using the currently available repertoire of immunotherapies.

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Nivolumab before and after allogeneic hematopoietic cell transplantation

Cited by 15 publications

References 14 publications

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint inhibitors: Feasibility and safety

Immune checkpoint inhibitors in the management of malignancies in transplant recipients

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