Immune Reconstitution following High-Dose Chemotherapy and Autologous Stem Cell Transplantation with or without Pembrolizumab Maintenance Therapy in Patients with Lymphoma

Merryman, Reid W.; Redd, Robert A.; Jeter, Erin; Wong, Joyce; McHugh, Kristin M; Reynolds, Carol; Nazzaro, Matthew; Varden, Aine; Brown, Jennifer R.; Crombie, Jennifer; Davids, Matthew S.; Fisher, David C.; Jacobsen, Eric; Jacobson, Caron A.; Kim, Austin I.; LaCasce, Ann S.; Ng, Samuel Y.; Odejide, Oreofe O.; Parry, Erin M.; Dahi, Parastoo B.; Nieto, Yago; Joyce, Robin; Chen, Yi-Bin; Herrera, Alex F.; Armand, Philippe; Ritz, Jérôme

doi:10.1016/j.jtct.2021.10.010

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…No unexpected safety signals were detected nor significant disturbances in post-transplant immune reconstitution kinetics [ 25 ]. Instead, consolidation with pembrolizumab was associated with earlier recovery of natural killer (NK) cells and a sustained elevation of circulating plasmacytoid and immature dendritic cells, whose possible impact on disease control remains to be determined [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, the search for robust predictive biomarkers to identify patients with a long-term response after anti-PD1 discontinuation has been mostly elusive [ 30 , 39 , 40 , 41 ]. Adopting anti-PD1 antibodies as a post-ASCT consolidation involves a biologically different situation due to the combined antitumor effects of HDT conditioning and transplant-related changes in PD1-expressing target immune cells [ 25 , 26 ]. Therefore, a fixed-duration therapy after ASCT may turn equally effective as a more prolonged treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Armand and coworkers showed that post-ASCT consolidation with single-agent pembrolizumab in patients with high RR-cHL yields an 18-month PFS of 82% with an OS of 100%. No unexpected safety signals nor disturbances in post-transplant immune reconstitution were detected [ 25 , 26 ]. Based on these results, other PD-1 blockers, such as nivolumab, alone and in combination with BV, are currently being tested as post-ASCT consolidation in patients with high-risk RR-HL [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

Filippi

Marcacci

Derenzini

et al. 2022

Cancers

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(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6–30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients’ subsets more likely to benefit from this approach.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

Filippi

Marcacci

Derenzini

et al. 2022

Cancers

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“…Anti-PD-1 monoclonal antibody (mAb) therapies reconstitute the immune surveillance of malignant cells, enabling a rapid reduction in Reed-Sternberg cells and PDL1+ inflammatory cells as well as a durable PD-1 blockade that persists even after treatment cessation based on patient samples during and after treatment [ 44 ]. A rise in CD4+ T cell receptors, dendritic cells, and mature, highly differentiated NK cells is seen in peripheral blood after anti-PD1 mAb treatment, correlating with earlier and more robust clinical response [ 44 , 45 , 46 , 47 ].…”

Section: Immune Checkpoints and The Tumor Microenvironment (Tme) In Chlmentioning

confidence: 99%

Updates in the Role of Checkpoint Inhibitor Immunotherapy in Classical Hodgkin’s Lymphoma

Nakhoda

Rizwan

Vistarop

et al. 2022

Cancers

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Classical Hodgkin’s lymphoma is a highly curable disease, but 10–25% of patients with higher-risk disease relapse. The introduction of checkpoint inhibitors (CPIs) targeting PD-1 have changed the landscape of treatment for patients with relapsed/refractory disease to multiple lines of therapy. The depth of response to CPI as a monotherapy is highest in the first relapse as salvage therapy based on outcomes reported in several phase II studies. With earlier use of CPI and brentuximab vedotin, the optimal sequencing of therapy is evolving. In this review, we will summarize clinical investigation of anti-PD-1 mAb in earlier line settings to provide insights on utilizing these agents as chemotherapy- and radiation-sparing approaches, increasing depth of response, and as part of combination regimens.

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“…[5,6] IR after hematopoietic stem cell transplantation (HSCT) is critical for control infection, GVHD, and enhanced antileukemia effects, [7][8][9][10] which can be affected by various factors such as conditioning regimen and stem cell source. [11,12] Waller et al [13] monitored the IR process in 410 patients after bone marrow or peripheral blood stem cell transplantation using flow cytometry and reported the time axis and differences in IR from different stem cell sources. Thus, the detection of lymphocyte subsets could be used to monitor patient condition after transplantation and may provide preemptive therapy.…”

Section: Introductionmentioning

confidence: 99%

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Pan,

Ding,

Huang

et al. 2023

Chinese Medical Journal

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Background: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking. Methods: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD. Results: The absolute number of DNT cells in the healthy Chinese population was 109 (70–157)/μL, accounting for 5.82 (3.98–8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23–0.93; P = 0.031). Conclusions: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

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Immune Reconstitution following High-Dose Chemotherapy and Autologous Stem Cell Transplantation with or without Pembrolizumab Maintenance Therapy in Patients with Lymphoma

Cited by 7 publications

References 39 publications

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study

Updates in the Role of Checkpoint Inhibitor Immunotherapy in Classical Hodgkin’s Lymphoma

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

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