Checkpoint blockade treatment sensitises relapsed/refractory non‐Hodgkin lymphoma to subsequent therapy

Abstract

Patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment. Seventeen North American centres retrospectively queried records. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment. Secondary aims included progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Fifty-nine patients (68% aggressive NHL, 69% advanced disease) were included. Patients received a median of three therapies before CBT. Fifty-three (90%) discontinued CBT due to progression. Post-CBT regimens included chemotherapy (49%), targeted therapy (30%), clinical trial (17%), transplant conditioning (2%) and chimeric antigen receptor T cell (CAR-T) therapy (2%). The ORR to post-CBT treatment was 51%, with median PFS of 6Á1 months. In patients with at least stable disease (SD) to post-CBT, the median DOR was significantly longer than to pre-CBT (310 vs. 79 days, P = 0Á005) suggesting sensitisation. Nineteen patients were transplanted after post-CBT therapy. Median overall survival was not reached, nor affected by regimen. Prospective trials are warranted, as this may offer R/R NHL patients a novel therapeutic approach.

Checkpoint Blockade Treatment May Sensitize Hodgkin Lymphoma to Subsequent Therapy

“…Another study showed that patients with NSCLC were more than three times more likely to achieve a partial response (PR) with salvage chemotherapy if they had prior exposure to CBT [8]. We have shown this same effect in a retrospective study of patients with non‐Hodgkin lymphoma (NHL), a disease where CBT does not appear to have much single‐agent activity [9, 10]. Given the significance of these findings, we investigated the outcome of CBT on subsequent treatment for patients with relapsed and refractory (R/R) HL in a large, multicenter, retrospective analysis.…”

Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

“…Carreau and colleagues showed that the overall response to subsequent therapy after checkpoint inhibition was 62% in 81 patients with relapsed refractory Hodgkin lymphoma 94 and 51% in 59 patients with relapsed refractory non-Hodgkin lymphoma. 95 With further studies, we are hopeful that biomarkers including PD-L1 expression, TMB, and MSI status will be used to best-select patients with hematologic malignancies for treatment with checkpoint blockade who are most likely to benefit.…”

Is it time to rethink checkpoint blockade therapy in non‐Hodgkin lymphoma?

“…It is usually assumed that increasing lines of therapy will result in decreasing response rates and DOR. Given that the trend was reversed in this study, with longer DOR to therapy after CBT, the authors argue that CBT may sensitise patients to subsequent treatments 5 . These provocative data are certainly hypothesis‐generating and provide an opportunity to re‐evaluate how we approach the use CBT in NHL, as a potential ‘sensitiser’ to chemotherapy, rather than as a single agent in refractory disease.…”

“…In this issue of the British Journal of Haematology , Carreau et al 5 . describe the outcomes of treatment beyond failure of CBT for NHL.…”

“…The retrospective study by Carreau et al 5 . reinvigorates the discussion about the potential role for combining CBT with other therapies in NHL and is of particular interest given that further data are unlikely to be forthcoming, with diminished interest in investigating single‐agent CBT in NHL.…”