Recommendations for managing PD-1 blockade in the context of allogeneic HCT in Hodgkin lymphoma: taming a necessary evil

Abstract

PD-1 blockade is an effective therapy in relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) who have relapsed after or are ineligible for autologous hematopoietic cell transplantation (HCT). Although single-agent anti-PD-1 monoclonal antibodies (mAb's) are associated with high response rates and durable remissions, available results to date suggest that a large majority of patients will eventually progress on therapy. Many of these patients are potential candidates for allogeneic HCT (allo-HCT) after receiving anti-PD-1 mAb's, and allo-HCT remains for now the only treatment with demonstrated curative potential in this setting. However, initial reports suggested that allo-HCT in this setting may be associated with increased risk of early transplant-related toxicity, likely driven by lingering effects of PD-1 blockade. Furthermore, many patients with R/R cHL who undergo allo-HCT will relapse after transplantation, most often with limited treatment options. Here again, PD-1 blockade appears to yield high response rates, but with an increased risk of attendant immune toxicity. Many questions remain regarding the use of PD-1 blockade before or after allo-HCT, especially in relation to the feasibility, outcome, optimal timing, and method of allo-HCT after PD-1 blockade. Despite the scarcity of prospective data, these questions are unavoidable and must be tackled by clinicians in the routine care of patients with advanced cHL. We provide consensus recommendations of a working group based on available data and experience, in an effort to help guide treatment decisions until more definitive data are obtained.

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

“…The patient died shortly thereafter of a sepsis‐like syndrome. Recently published consensus‐based guidelines have been put forth regarding the use and toxicity of checkpoint inhibitors either prior to or following allogeneic SCT .…”

“…The patient died shortly thereafter of a sepsis-like syndrome. Recently published consensus-based guidelines have been put forth regarding the use and toxicity of checkpoint inhibitors either prior to or following allogeneic SCT [20]. A history of autoimmunity has previously been thought to confer a higher risk of toxicity to PD-1 inhibitors; therefore, patients with such a history have been excluded from clinical trials with these drugs.…”

“…At the time of data collection, 16 patients (31%) remained on the original PD-1 inhibitor. For those patients who remained on therapy at the data cutoff, median duration of treatment with a PD-1 inhibitor was 21 months (range, 2-34); among patients who discontinued therapy, median treatment duration was 6 months (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Nine of the 24 patients (38%) who achieved CR remained on the original PD-1 inhibitor at the data cutoff; those with CR who discontinued the PD-1 inhibitor did so because of toxicity (4, 17%), autoSCT (2, 8%), disease progression (1, 4%), or patient or physician preference (7, 29%).…”

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

“…This CPI use has led to many serious immune related side effects (i.e., autoimmune diseases) and data is emerging on serious and potentially fatal GVHD in patients who undergo allo-HSCT (2, 4, 5). Researchers have strongly recommended starting PD-1 blockers at low doses and close monitoring of patients for signs of GVHD, when using in pre or post allo-HSCT settings for patients with relapsed or refractory classical Hodgkin lymphoma (6). There is a paucity of data on the safety and efficacy regarding the use of CPI in the peri-allo-HSCT setting.…”

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies

“…Given the complexity of patient and timing selection, specific recommendations on the application of PD-1 inhibitors in the context of alloSCT have been published recently: experts in the field recommend to keep responders on PD-1 inhibitors rather than stopping treatment and proceeding to alloSCT, whereas heavily pretreated patients due to multiply refractory disease are the ones who should be considered for an early alloSCT, after response to PD-1 treatment. 232 For patients scheduled for alloSCT, a 6-week PD-1 treatment-free period is recommended before the procedure. Other considerations include the use of bone marrow grafts instead of peripheral blood, the use of PtCy for GvHD prevention, and prompt implementation of GvHD treatment.…”