David J. Straus, MD
Since the FDA approval of nivolumab (Opdivo) in May 2016, researchers continue to explore the agent as well as its fellow PD-1 inhibitor, pembrolizumab (Keytruda), in various treatment settings for patients with Hodgkin lymphoma.
In 12-month follow-up results of the phase II CheckMate-205 trial presented at the 2016 ASH Annual Meeting,1
patients with classical Hodgkin lymphoma (cHL) who received brentuximab vedotin (Adcetris) after autologous hematopoietic stem cell transplantation (AHSCT) treated with nivolumab had an overall response rate (ORR) of 67.5%, with a duration of response of 13.1 months (95% CI, 8.7-NA). The median progression-free survival was 14.8 months.
Results from a separate CheckMate-205 cohort supported the FDA’s approval of nivolumab for patients with cHL who relapse or progress after AHSCT and posttransplantation brentuximab vedotin.
In December 2016, the FDA granted a priority review to a supplemental biologics license application for pembrolizumab as a treatment for patients with refractory cHL or those who have relapsed after ≥3 lines of therapy. This is based on findings from the phase II KEYNOTE-087 and phase Ib KEYNOTE-013 trials, which evaluated pembrolizumab for the proposed indication in the application.2
In an interview, David J. Straus, MD, an internist and hematologic oncologist at Memorial Sloan Kettering Cancer Center, provides an overview on recent findings and future directions in Hodgkin lymphoma. Straus spoke on these topics during the 2016 OncLive®
State of the Science Summit on Hematologic Malignancies.
OncLive: Can you provide a recap of your talk on Hodgkin lymphoma?
: The first portion was on overall results in a rare type of Hodgkin lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, which is about 5% of Hodgkin lymphoma. It is different biologically, as well as clinically, from cHL in that it is a lymphoma with a mature B-cell phenotype. It also has a behavior with an excellent prognosis, but late recurrences—somewhat akin to low-grade B-cell non-Hodgkin lymphoma (NHL). This is a disease where there is no evidence of a decreased survival at diagnosis. Also, there are little data to suggest that any treatment affects the overall outcome.
This was a look at patients who relapse after initial treatment on various studies of the German Hodgkin Study Group, which puts a lot of patients on treatment. They had various protocols that they use for cHL. They ended up with 99 patients who relapsed after their initial treatment. They did not include patients who transformed to an aggressive NHL, which is the clearest indication for treatment.
The bottom line was that everybody did great. They used various treatments, including autologous transplant. The survivals were close to 90% to 100% for whatever they did. In these 99 patients, they only had 10 deaths, 5 of which were due to nodular lymphocyte-predominant Hodgkin lymphoma and 5 due to treatment, including 3 secondary malignancies, 1 infection, and 1 pulmonary failure.
The other 3 abstracts I covered pertained to the use of checkpoint inhibitors. Two of them had really been tested extensively and involved the PD-1 inhibitors pembrolizumab and nivolumab. Both of these have excellent, high response rates in very heavily pretreated patients after autologous transplants and usually after brentuximab vedotin.
The 2016 ASH Annual Meeting was the first time both of these were presented in full form. Nivolumab was actually published by my colleague Eunice L. Kwak, MD, PhD. The excellent results led to an accelerated FDA approval for nivolumab in patients with Hodgkin lymphoma who relapse after autologous transplant and who fail brentuximab vedotin.
Both the pembrolizumab and nivolumab trials had 3 cohorts. Basically, they were relapse/refractory patients after autologous transplants, most of whom had brentuximab vedotin, which is the label for nivolumab, but some of them did not have brentuximab vedotin. There were some patients who were not candidates for transplants; most of them were older patients who, for 1 reason or another, were not fit to undergo transplant.
The bottom line is that they all showed an ORR of around 65% in all cohorts in both drugs, within the complete response rate of about 22%. They had longer follow-up data than had been shown before, which demonstrated durable responses. Most of the responses occurred after 2 to 3 months.
The last one was a combination of nivolumab with brentuximab vedotin prior to transplant in relapsed patients after first-line treatment. They gave 4 cycles of the 2 drugs together. In the first cycle, they staggered the drugs. In the second, third, and fourth cycle, they gave them together. Approximately 20% of patients on this follow-up had gone on to autologous transplant. They had good stem cell collection. The ORR was quite impressive at around 90%, and there was around a 60% to 65% complete response rate—which is very impressive.