PD-1 Blockade in Mediastinal Gray-Zone Lymphoma

Melani, Christopher; Major, Ajay; Schowinsky, Jeffrey; Roschewski, Mark; Pittaluga, Stefania; Jaffe, Elaine S.; Pack, Svetlana D.; Abdullaev, Zied; Ahlman, Mark A.; Kwak, Jennifer; Morgan, Rustain; Rabinovitch, Rachel; Pan, Zenggang; Haverkos, Bradley M.; Gutman, Jonathan A.; Pollyea, Daniel A.; Smith, Clayton A.; Wilson, Wyndham H.; Kamdar, Manali

doi:10.1056/nejmc1704767

Cited by 51 publications

(38 citation statements)

References 5 publications

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“…Other translocations can be associated with a subset of DLBCL, such as primary mediastinal B lymphoma (PMBL). The 9p24.1 translocation found in PMBL, especially in grey‐zone lymphoma, is associated with a dramatic response rate to the immune checkpoint inhibitor anti‐PD1 (also termed anti‐PDCD1) (Melani et al , ), providing a good example of the evolution of biology related to targeted treatment. With the development of new technologies, such as whole‐exome sequencing, it will be possible to reveal novel disease drivers and risk groups (Reddy et al , ) and design more rational targeted therapy (Sehn & Gascoyne, ).…”

Section: How To Manage Patients At the First Relapsementioning

confidence: 99%

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

2018

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SummaryDespite progress in the upfront treatment of diffuse large B cell lymphoma (DLBCL), patients still experience relapses. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second‐line treatment for relapsed and refractory (R/R) DLBCL. However, half of the patients will not be eligible for transplantation due to ineffective salvage treatment, and the other half will relapse after ASCT. In randomized studies, no salvage chemotherapy regimen is superior to another. The outcomes are affected by the secondary International Prognostic Index at relapse and various biological factors. The strategy is less clear in patients who require third‐line treatment. A multicohort retrospective non‐Hodgkin lymphoma research (SCHOLAR‐1) study conducted in 636 patients with refractory DLBCL showed an objective response rate of 26% (complete response 7%) to the next line of therapy with a median overall survival of 6·3 months. In the case of a response followed by transplantation, long‐term survival can be achieved in DLBCL patients. There is clearly a need for new drugs that improve salvage efficacy. Encouraging results have been reported with chimeric antigen receptor ‐T cell engineering, warranting further studies in a well‐defined control group of refractory patients. The Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) was used as a handy framework to build the discussion.

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Section: How To Manage Patients At the First Relapsementioning

confidence: 99%

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

2018

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“…Based upon recent reports, the patient's situation drove our decision toward novel therapeutic modalities including checkpoint inhibition and the use of ruxolitinib. 10,17,18 To our knowledge, we describe the first pediatric GZL patient receiving pembrolizumab. However, in contrast to the three successfully treated adult cases described by Melani et al, 10 PD-1 blockade had to be omitted in our patient upon reprogression with loss of 9p24.1 amplification and due to severe pembrolizumabassociated colitis.…”

Section: Discussionmentioning

confidence: 98%

Management of children and adolescents with gray zone lymphoma: A case series

Perwein

Lackner

Ebetsberger‐Dachs

et al. 2020

Pediatric Blood & Cancer

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Background Data on management of gray zone lymphoma (GZL) in children and adolescents are scarce. Procedure This retrospective study assessed clinical characteristics and outcome in six Austrian patients with GZL less than 18 years of age (male‐to‐female ratio: 1:1; median age: 15.8 years). Results Two patients each had a classical Hodgkin lymphoma (cHL)‐like and composite GZL subtype, and one patient each had a large B‐cell non‐Hodgkin lymphoma (LBCL)‐like and sequential GZL subtype. All had advanced disease with mediastinal and extranodal involvement. Five patients received an LBCL‐ and one patient a cHL‐directed polychemotherapy ± radiotherapy. Out of the former patients, three survived, including two who relapsed and underwent high‐dose chemotherapy with autologous stem cell rescue. The latter patient survived. Conclusions GZL remains a diagnostic and therapeutic challenge, necessitating the development of novel treatment concepts performed in a prospective setting.

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“…Future studies should evaluate incorporating post-transplantation consolidation or maintenance strategies incorporating new therapies, especially in patients who are at higher risk of relapse. Anecdotal data show that PD-1 blockade is capable of inducing CR in patients with refractory GZL [20].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Gray Zone Lymphoma: A US Multicenter Collaborative Study

Kharfan‐Dabaja

Raj

Nikolaenko

et al. 2018

Biology of Blood and Marrow Transplantation

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High-dose therapy (HDT) and autologous hematopoietic cell transplantation (auto-HCT) has been anecdotally prescribed in gray zone lymphoma (GZL), showing encouraging efficacy. We conducted a multicenter retrospective study aimed at assessing outcomes after auto-HCT in 32 patients with GZL treated at 9 transplantation centers in the United States. The median age of patients at transplantation was 38 years (range, 18 to 70 years), and the majority were male (n = 21; 66%). The median number of lines of therapy before transplantation was 2 (range, 1 to 4). BEAM was the most commonly prescribed regimen (n = 23; 72%). The median duration of follow-up for surviving patients was 34 months (range, 1 to 106 months). Median overall survival (OS) was not reached. The 3-year progression-free survival (PFS) and OS for all patients were 69% and 78%, respectively. Three-year PFS and OS were 100% for patients who received only 1 line of therapy before auto-HCT versus 65% (PFS, P = .25) and 75% (OS, P = .39) for those receiving >1 line. The cumulative incidence of relapse/progression was 4% at 1 year post-transplantation and 31% at 3 years post-transplantation. The 3-year nonrelapse mortality was 0%. These findings suggest that HDT and auto-HCT is an effective treatment in patients with GZL. Our findings ideally require confirmation in a larger cohort of patients, preferably in the setting of large prospective multicenter randomized controlled trials. However, we acknowledge that such studies could be difficult to conduct in patients with GZL owing to the disease's rarity. Alternatively, a multicenter prospective study that includes tissue banking and a data registry is warranted to help better understand the biology and natural history of the disease.

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PD-1 Blockade in Mediastinal Gray-Zone Lymphoma

Cited by 51 publications

References 5 publications

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

Management of children and adolescents with gray zone lymphoma: A case series

Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Gray Zone Lymphoma: A US Multicenter Collaborative Study

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