Safety and efficacy of anti-programmed cell death-1 monoclonal antibodies before and after allogeneic hematopoietic cell transplantation for relapsed or refractory Hodgkin lymphoma: a multicenter retrospective study

Ito, Ayumu; Kim, Sung Won; Matsuoka, Ken; Kawakita, Toshiro; Tanaka, Takashi; Inamoto, Yoshihiro; Toubai, Tomomi; Fujiwara, Shin ichiro; Fukaya, Masafumi; Kondo, Tadakazu; Sato, Junichi; Nara, Miho; Katsuoka, Yoji; Imai, Yosuke; Nakazawa, Hayakazu; Kawashima, Ichiro; Sakai, Rika; Ishii, Arata; Onizuka, Makoto; Takemura, Tomonari; Terakura, Seitaro; Iida, Hiroatsu; Nakamae, Mika; Higuchi, Kohei; Tamura, Shinobu; Yoshioka, Satoshi; Togitani, Kazuto; Kawano, Noriaki; Suzuki, Ritsuro; Suzumiya, Junji; Izutsu, Koji; Teshima, Takanori; Fukuda, Takahiro

doi:10.1007/s12185-020-02960-4

Cited by 19 publications

(21 citation statements)

References 42 publications

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“…Table 1 summarizes previous studies on allo-HCT after PD-1 blockade [2,[8][9][10][11]. Although patient characteristics and transplant procedures were heterogeneous between studies, immune-related complications early after allo-HCT were frequent.…”

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

“…Regarding chronic GVHD, the follow-up periods were not long enough, and the data on the proportion of moderate-to-severe disease was not available in most studies (Table 1). In a Japanese cohort, the cumulative incidence of moderate-to-severe chronic GVHD was 34.1% at 1 year after allo-HCT [11], which was higher than those observed in the pre-anti-PD-1 blockade era [4,6]. Reported treatment-related complications included veno-occlusive disease/sinusoidal obstruction syndrome, which occurred at high incidences (7-8%) in 3 of the 5 studies even though a large proportion of patients received reduced-intensity conditioning (RIC) [8][9][10].…”

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

“…Merryman et al reported that > 80 days from the last dose to allo-HCT was associated with a lower risk of grade II-IV (hazard ratio (HR), 0.4; P = 0.04) and grade III-IV (HR, 0.4; P = 0.01) acute GVHD, but intervening chemotherapy between PD-1 blockade and allo-HCT was associated with a higher risk of relapse (HR, 2.9; P = 0.003) [12]. Recent studies showed that PTCy is an especially promising strategy to reduce GVHD in this setting [11,12,[14][15][16]. Paul et al reported that among 105 cHL patients who received RIC allo-HCT with PTCy, the GVHD and NRM rates were comparable between individuals who received an immune checkpoint inhibitor (ICI) before allo-HCT and those who did not (grade II-IV acute GVHD, 33% vs. 17%, respectively; P = 0.11; chronic GVHD, 3% vs. 14%, respectively; P = 0.19) [16].…”

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

“…It is controversial whether anti-thymocyte globulin (ATG) effectively reduces GVHD associated with allo-HCT after PD-1 blockade. In a Japanese cohort, ATG (Thymoglobu-lin™) was used in 7 patients at a median dose of 2.00 mg/ kg (range 1.25-3.00) and did not reduce acute GVHD [11]. Conversely, in an international retrospective cohort, ATG was used in 46 patients, and there was a trend toward reduced acute GVHD among patients who received ATG (HR, 0.5; P = 0.058) [12].…”

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

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Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review

Ito¹,

Kim²,

Fukuda³

2022

Int J Hematol

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Approximately 10-30% of patients with classic Hodgkin lymphoma (cHL) have relapsed or refractory (r/r) disease after standard first-line therapy. Clinical trials have shown an acceptable safety profile and high response rate for anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) in patients with r/r cHL. Although anti-PD-1 mAbs have significantly increased treatment options for r/r cHL, most patients eventually relapse. In the current era, allogeneic hematopoietic cell transplantation (allo-HCT) is still a clinical option for r/r cHL. Anti-PD-1 mAbs have been explored as bridging therapy to allo-HCT and salvage therapy for relapse after allo-HCT. Although early reports showed increased risks of severe graftversus-host disease (GVHD) in patients who received anti-PD-1 mAb before or allo-HCT, survival outcomes were favorable, suggesting the feasibility of PD-1 blockade around the time of allo-HCT. Based on clinical and biological data, posttransplant cyclophosphamide-based GVHD prophylaxis is a promising strategy to reduce GVHD and improve survival after allo-HCT following PD-1 blockade. Close monitoring and early intervention are needed for treatment-emergent GVHD following PD-1 blockade after allo-HCT. Further studies with a larger cohort and extended follow-up will provide insights into better patient selection, optimal dosing, and strategies to manage complications of PD-1 blockade in the context of allo-HCT.

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Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

Section: Allo-hct After Anti-pd-1 Mab Therapymentioning

confidence: 99%

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Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review

Ito¹,

Kim²,

Fukuda³

2022

Int J Hematol

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“…71 Data from two small studies of anti-PD-1 suggest that prophylactic cyclophosphamide post-transplant may improve GVHD-related outcomes in this population. 72,73 In a systematic review of 19 studies, receiving ICI [ipilimumab (n ¼ 85), nivolumab (n ¼ 76), pembrolizumab (n ¼ 16)] after allo-HSCT had high efficacy (ORR: 54%) and risk of GVHD (14% acute, 11% chronic), with a GVHD mortality risk of 7%. 70 Incidentally, historical rates of GVHD in patients without any ICI exposure (before or after) were found to be 30%-50% for acute 70,74 and up to 28% for de novo chronic GVHD.…”

Section: Immunodeficiency Including Transplant Recipientsmentioning

confidence: 99%

Immunotherapy use outside clinical trial populations: never say never?

et al. 2021

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Background: Based on favourable outcomes in clinical trials, immune checkpoint inhibitors (ICIs), most notably programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, are now widely used across multiple cancer types. However, due to their strict inclusion and exclusion criteria, clinical studies often do not address challenges presented by non-trial populations. Design: This review summarises available data on the efficacy and safety of ICIs in trial-ineligible patients, including those with autoimmune disease, chronic viral infections, organ transplants, organ dysfunction, poor performance status, and brain metastases, as well as the elderly, children, and those who are pregnant. In addition, we review data concerning other real-world challenges with ICIs, including timing of therapy switch, relationships to radiotherapy or surgery, re-treatment after an immune-related toxicity, vaccinations in patients on ICIs, and current experience around ICI and coronavirus disease-19. Where possible, we provide recommendations to aid the oftendifficult decision-making process in those settings. Conclusions: Data suggest that ICIs are often active and have an acceptable safety profile in the populations described above, with the exception of PD-1 inhibitors in solid organ transplant recipients. Decisions about whether to treat with ICIs should be personalised and require multidisciplinary input and careful counselling of patients with respect to potential risks and benefits. Clinical judgements need to be carefully weighed, considering factors such as underlying cancer type, feasibility of alternative treatment options, or activity in trial-eligible patients.

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Clinical Experiences with Immune Checkpoint Inhibitors in Lymphomas

Timmerman

2024

Precision Cancer Therapies Vol 2 ‐ Immunologic Approaches for the Treatment of Lymphoid Malignancies ‐ From Concept to Practice

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Safety and efficacy of anti-programmed cell death-1 monoclonal antibodies before and after allogeneic hematopoietic cell transplantation for relapsed or refractory Hodgkin lymphoma: a multicenter retrospective study

Cited by 19 publications

References 42 publications

Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review

Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review

Immunotherapy use outside clinical trial populations: never say never?

Clinical Experiences with Immune Checkpoint Inhibitors in Lymphomas

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