Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma

Cheikh, Jean El; Massoud, Radwan; Abu-Dalle, Iman; Haffar, Basel; Mahfouz, Rami; Kharfan-Dabaja, M.; Jisr, T.; Mougharbel, Anas; Ibrahim, Ahmad; Bazarbachi, Ali

doi:10.1038/bmt.2017.69

Cited by 41 publications

(31 citation statements)

References 15 publications

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“…We found that the incidence of GVHD was 60% versus 70%, but the number of patients in each group was very limited. Increased rate of efficacy with GVT effect correlated positively with increasing risk of GVHD activity (grade 2–4) in three studies (5, 10, 27), complementing the association between GVT and GVHD, as previously reported in animal studies which tested PD-1 blockade (31, 32). US Food and Drug Administration (FDA) has issued label warnings for use of HSCT after prior PD-1 blockade.…”

Section: Discussionsupporting

confidence: 81%

“…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%

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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

150

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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: Discussionsupporting

confidence: 81%

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

150

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“…Unfortunately, a significant number of patients with relapsed/refractory HL have chemo‐resistant disease and have received multiple lines of therapy. Therefore, novel monoclonal antibodies, such as brentuximab vedotin (BV), or checkpoint inhibitors are increasingly used as a bridge to transplant (Chen et al , , ; Ansell et al , ; Illidge et al , ; El Cheikh et al , ; Hegerova et al , ; Merryman et al , ).…”

mentioning

confidence: 99%

Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party

et al. 2018

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Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre-transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow-up for survivors was 41 months. Patients in the BV group were more heavily pre-treated (median pre-allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre-allograft BV had no impact on acute graft-versus-host disease (GVHD), non-relapse mortality, cumulative incidence of relapse, progression-free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45-0·92; P < 0·02). Older age, poor performance status, use of pre-transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.

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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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Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma

Cited by 41 publications

References 15 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

Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party

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

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