Efficacy of chemotherapy or chemo‐anti‐PD‐1 combination after failed anti‐PD‐1 therapy for relapsed and refractory hodgkin lymphoma: A series from lysa centers

Abstract

Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pre-treated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n=24) and partial response (PR) (n=6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95%CI, 6.3; not reached) and the median of overall survival was not reached. These observations in highly pre-treated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT. This article is protected by copyright. All rights reserved.

Early 18F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

“…(11) Second, recent reports suggested that anti PD-1 mAb could be discontinued in patients achieving complete metabolic response (31) and that more aggressive strategies (i.e., addition of chemotherapy, consolidation with allograft) may be required for patients who are unable to achieve a complete response. (32) The limitations of this study are the retrospective analysis of a multicenter population of patients with moderate sample size. First, the sample size is small compared to datasets evaluating standard of care drugs.…”

Effectiveness of chemotherapy after anti‐PD‐1 blockade failure for relapsed and refractory Hodgkin lymphoma

“…Based on a rationale that DNA damaging agents are able to promote immunogenicity of cancer cells trough increasing neo‐antigen repertoire, inducing immunogenic cell death and changing the cytokine milieu into the tumor microenvironment, with a consequence redistribution and increase expression of PDL‐1 on tumor cells, good results are being achieved combining PD1 inhibitors with chemotherapy, both in solid tumors and in lymphomas setting 20‐24 . On the other side, patients who already failed anti‐PD1 therapy, seems to benefit from a re‐treatment with conventional CHT, leading to the idea that PD1 inhibitors can re‐sensitize tumor cells to conventional treatment, previously failed 12,13 . Rossi et al showed an overall response in 16 (67%) out of 30 R/R HL patients treated with conventional CHT after anti‐PD1 treatment (CR: 46%), regardless of whether patients had been re‐exposed to an agent to which they were previously resistant.…”

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

“…182 Besides evidence supporting the optimization of tumor response to PD1-blockade with the addition of hypomethylating agents, a retrospective trial of 30 patients with rr-cHL and unsatisfactory response to anti-PD1 therapy proposed the beneficial effect of previous checkpoint blockade on the following chemotherapy administration, either alone or in combination with the previous anti-PD1 agent, by demonstrating 61% and 90% objective response rates in the 'sequential' and 'combination' strategy, respectively. 183 Recently, Carreau and colleagues evaluated 77 heavily pretreated cHL patients who received a subsequent line of therapy after anti-PD1 blockade.…”