Programmed death 1 expression in the peritumoral microenvironment is associated with a poorer prognosis in classical Hodgkin lymphoma

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 7507-7514 ◽  
Author(s):  
Young Wha Koh ◽  
Yoon Kyung Jeon ◽  
Dok Hyun Yoon ◽  
Cheolwon Suh ◽  
Jooryung Huh
Keyword(s):  
Hodgkin Lymphoma ◽  
Classical Hodgkin Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Final results of a phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma

2020 ◽  
Vol 50 (11) ◽  
pp. 1265-1273
Author(s):  
Dai Maruyama ◽  
Yasuhito Terui ◽  
Kazuhito Yamamoto ◽  
Noriko Fukuhara ◽  
Ilseung Choi ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Hodgkin Lymphoma ◽  
Adverse Drug Reactions ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Japanese Patients ◽  
Classical Hodgkin Lymphoma ◽  
Drug Reactions ◽  
Programmed Death ◽  
Programmed Death 1

Abstract Background Many patients with classical Hodgkin lymphoma show increased programmed death-1 ligand expression in Reed–Sternberg cells. We report the final results of a phase II study of nivolumab, an anti-programmed death-1 monoclonal antibody, in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Methods Japanese patients with previously treated classical Hodgkin lymphoma (aged ≥ 20 years) were administered nivolumab (3 mg/kg on Day 1 of 14-day cycles) until progressive disease, an unacceptable adverse event, or another clinically relevant reason. Treatment could continue beyond progressive disease at the investigator’s discretion in selected patients. Results Seventeen patients (median age: 63.0 years) were enrolled. The median follow-up was 38.8 months. One patient with non-Hodgkin lymphoma was excluded from efficacy analyses. The centrally assessed overall response rate in 16 classical Hodgkin lymphoma patients was 87.5% (95% confidence interval = 61.7–98.4%) and the disease control rate was 93.8% (95% confidence interval = 69.8–99.8%). The median (95% confidence interval) duration of response and progression-free survival were 8.5 (2.4–12.6) and 11.7 (1.8–42.3) months, respectively. The 3-year overall survival rate was 80.4% (95% confidence interval = 50.6–93.2%). Nivolumab was continued beyond progressive disease in seven patients; six were alive at the data cut-off. Adverse drug reactions occurred in all 17 patients with grades 3–4 adverse drug reactions in eight patients and no grade 5 adverse drug reactions. Pulmonary toxicities occurred in five patients; four of these occurred ≥17 months after starting nivolumab. Conclusion Nivolumab is effective and tolerable in Japanese relapsed or refractory classical Hodgkin lymphoma patients. Continued monitoring may be necessary to detect late-onset pulmonary toxicities. Clinical trial registration JapicCTI-142755 (Japan Pharmaceutical Information Center).

scholarly journals Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure

2016 ◽  
Vol 34 (31) ◽  
pp. 3733-3739 ◽  
Author(s):  
Philippe Armand ◽  
Margaret A. Shipp ◽  
Vincent Ribrag ◽  
Jean-Marie Michot ◽  
Pier Luigi Zinzani ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Cell Receptor ◽  
Interferon Γ ◽  
Genetic Alterations ◽  
Brentuximab Vedotin ◽  
Response To Treatment ◽  
Classical Hodgkin Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1

Purpose Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations leading to overexpression of the programmed death-1 (PD-1) ligands, suggesting a possible vulnerability to PD-1 blockade. The phase Ib study KEYNOTE-013 (NCT01953692) tested the safety and efficacy of the anti–PD-1 antibody pembrolizumab in patients with hematologic malignancies. Based on its genetics, HL was included as an independent cohort. Methods We enrolled patients with relapsed or refractory HL whose disease progressed on or after treatment with brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, until disease progression occurred. Response to treatment was assessed at week 12 and every 8 weeks thereafter. Principal end points were safety and complete remission (CR) rate. Results Thirty-one patients were enrolled; 55% had more than four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation. Five patients (16%) experienced grade 3 drug-related adverse events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR rate was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial remission, for an overall response rate of 65% (90% CI, 48% to 79%). Most of the responses (70%) lasted longer than 24 weeks (range, 0.14+ to 74+ weeks), with a median follow-up of 17 months. The progression-free survival rate was 69% at 24 weeks and 46% at 52 weeks. Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-γ, T-cell receptor, and expanded immune-related signaling pathways. Conclusions Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.

Abscopal effect in a Hodgkin lymphoma patient treated by an anti-programmed death 1 antibody

2016 ◽  
Vol 66 ◽  
pp. 91-94 ◽  
Author(s):  
Jean-Marie Michot ◽  
Renaud Mazeron ◽  
Laurent Dercle ◽  
Samy Ammari ◽  
Charles Canova ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Abscopal Effect ◽  
Lymphoma Patient ◽  
Hodgkin Lymphoma Patient ◽  
Programmed Death ◽  
Programmed Death 1

Programmed death-1 (PD-1) and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e19514-e19514
Author(s):  
Semra Paydas ◽  
Emine Bagir ◽  
Melek Ergin ◽  
Berna Bozkurt Duman ◽  
Vehbi Ercolak
Keyword(s):  
Hodgkin Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1

Programmed Death Ligand 1 Expression in Classical Hodgkin Lymphoma in Pediatric Patients

2018 ◽  
Vol 40 (4) ◽  
pp. 334-335
Author(s):  
Takahiro Aoki ◽  
Masashi Kyushiki ◽  
Hiroshi Kishimoto ◽  
Masato Yanagi ◽  
Makiko Mori ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Pediatric Patients ◽  
Classical Hodgkin Lymphoma ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals Where Do Programmed Death-1 Inhibitors Fit in the Management of Malignant Lymphoma?

2016 ◽  
Vol 12 (2) ◽  
pp. 101-106 ◽  
Author(s):  
Stephen M. Ansell
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Hodgkin Lymphoma ◽  
Cytotoxic T Cells ◽  
Single Agent ◽  
Antitumor Immune Response ◽  
Non Hodgkin Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1

Tumor-specific cytotoxic T cells have the capacity to target and eradicate malignant B cells in patients with Hodgkin and non-Hodgkin lymphoma; however, multiple mechanisms, including regulatory T cells, immunosuppressive ligands, and immune exhaustion, suppress an effective antitumor immune response. One mechanism that is used by malignant cells to inhibit the immune response is overexpression of programmed death ligand 1 or 2 (PD-L1 or PD-L2) on the cancer cell surface. These ligands interact with the programmed death-1 (PD-1) receptor expressed on intratumoral T cells and provide an inhibitory signal, thereby suppressing the antitumor immune response. Monoclonal antibodies that block PD-1 signaling prevent T-cell inhibition and promote a T-cell–mediated antilymphoma response. Blocking antibodies that are directed against PD-1 or PD-L1 are currently being tested in patients with lymphoma and have shown remarkable efficacy, particularly in patients with relapsed Hodgkin lymphoma. On the basis of the promising activity of this approach, PD-1 inhibitors are being used as single-agent therapy in patients with relapsed Hodgkin lymphoma, and these inhibitors are also being tested in combination with standard chemotherapy or targeted agents in ongoing clinical trials.

scholarly journals Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial

2018 ◽  
Vol 36 (14) ◽  
pp. 1428-1439 ◽  
Author(s):  
Philippe Armand ◽  
Andreas Engert ◽  
Anas Younes ◽  
Michelle Fanale ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Objective Response Rate ◽  
Hematopoietic Cell Transplantation ◽  
Response Rate ◽  
Objective Response ◽  
Classic Hodgkin Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Autologous Hematopoietic Cell Transplantation

Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)–naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.

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