Patients with both Hodgkin’s and non-Hodgkin’s lymphoma who receive immune checkpoint inhibitors as their second-line or later treatment might respond better to their subsequent therapy, even if they failed to respond or progressed after checkpoint inhibitor treatment, two recent studies suggest.
The studies, “Checkpoint Blockade Therapy May Sensitize Aggressive and Indolent Non-Hodgkin Lymphoma to Subsequent Therapy” and “Checkpoint Blockade Therapy May Sensitize Hodgkin Lymphoma to Subsequent Therapy,” were presented at the American Society of Hematology (ASH) 2018 Annual Meeting.
Immune checkpoint inhibitors, including Opdivo (nivolumab) and Keytruda (pembrolizumab), block inhibitory signals that cancer cells can send immune cells, preventing the immune cells from attacking the tumor. By removing this inhibitory signal, checkpoint inhibitors can allow immune cells to more effectively kill cancer cells.
Yet this therapy often shows only modest results, and researchers were particularly interested in those patients who had been given checkpoint inhibitors after failing at least one prior treatment, had seen progressive disease, and then had been given a different therapy.
The researchers wondered whether the immunotherapy, even if it wasn’t successful in totally controlling the cancer on its own, might “prime” the tumor to be more vulnerable to subsequent treatment with traditional chemotherapy, targeted therapies, or investigational agents in clinical trials.
In the studies, medical records from lymphoma patients treated at 17 centers across the United States between 2012 and 2018 were reviewed. Both studies had similar designs, but analyzed patients with non-Hodgkin’s or Hodgkin’s lymphoma respectively.
The results supported the hypothesis. Among the 59 patients with non-Hodgkin’s lymphoma, only 10% had responded to checkpoint inhibitors, and their responses to the prior treatment had only lasted a median of two months. However, 51% of these patients responded to additional treatment, and they remained alive and progression-free for 12.5 months. Of the 29 patients still surviving and receiving subsequent therapy, 16 have seen no worsening of the disease.
Similarly, of the 81 Hodgkin’s lymphoma patients who required additional therapy after checkpoint inhibitor treatment, 66 are still alive, and 30 have seen no disease progression. In these patients, response to subsequent therapy correlated with response to the checkpoint inhibitor; that is, patients who had a good initial response to the checkpoint inhibitor were more likely to respond well to subsequent treatment.
“These are very high success rates for post-checkpoint blockade therapy, especially in patients for whom several drug therapies have failed, including the same or similar drugs used again after checkpoint therapy,” Catherine Diefenbach, senior author on both studies, said in a press release.
Diefenbach cautioned that future prospective studies — which monitor patients over the course of their treatment, rather than retroactively analyzing records — will be needed before scientists can say with certainty whether immunotherapy makes lymphomas more vulnerable to future treatments.
