Philippe Armand, MD, MPH
Amid continuing excitement over the potential for PD-1 pathway immune checkpoint blockade strategies in anticancer therapies, research presented at the 2014 American Society of Hematology (ASH) Annual Meeting in San Francisco in December helped established a foundation for the use of anti- PD-1/PD-L1 agents in hematologic malignancies. Philippe Armand, MD, MPH, of Harvard Medical School, and Alexander Lesokhin, MD, of Memorial Sloan Kettering Cancer Center, are among the leading researchers in the field. They discussed their recent findings and other key questions in separate interviews with OncologyLive.OncLive: Until now, success with PD-1 pathwaytargeting agents was seemingly limited to solid tumors. What has driven the more recent successes in hematologic malignancies?Armand
: Because of the success in the solid tumor world, many people were interested in bringing the drugs into hematologic malignancies. In most diseases, it’s a little bit of a shot in the dark, although there is a fair amount of preclinical evidence for at least the presence of PD-L1 on some of the malignant cells in some of the tumors. The one disease that is different in this respect is classical Hodgkin lymphoma (cHL) because there’s already very strong science to show that this disease is different from the others. cHL very often has a genetic abnormality that amplifies the genetic material on the short arm of the 9th chromosome and this results in increased expression of the PD-1 ligands, specifically PD-L1 and PD-L2. It’s something that hasn’t been shown before for any solid tumor and very few hematologic malignancies, which implies that HL may have a different behavior under PD-1 blockade than the other set of diseases. Can you briefly discuss the significance of research presented at ASH?Armand:
There were two studies that were presented on PD-1 blockade in cHL. That’s where the results are the most promising. The studies were similar, the treatments were similar; one treated 23 patients and one treated 31 but analyzed 29 patients. The overall results in terms of response rates and apparent duration of response were also similar. In the nivolumab study,1 which treated 23 patients, the overall response rate was 87% with 13% complete remission. In the pembrolizumab study,2 the overall response rate was 65% with 21% complete remission. It seems from relatively early data that the responses may be durable and there are patients who are over 1 year in response already. So both studies really supported a strong activity of these drugs and they were both done in populations of very advanced patients, most of whom had already failed prior transplant and prior brentuximab. So these were patients who were very heavily pretreated who had these phenomenal responses.
A third study 3
was on non-Hodgkin lymphoma and multiple myeloma using nivolumab, and there the results were interesting but a little bit less definitive. There were some histologies like large cell lymphoma, follicular lymphoma (FL), and T-cell lymphoma where some of the patients responded, but the response rates were more in the 30% to 40% range in a very small number of patients. That is certainly a strong signal, but there were a small number of patients and the responses seem less durable, so more work is needed to understand the biology that underlies this phenomenon.Lesokhin:
I think the activity [in HL] is remarkable. I participated in the nivolumab study.1 I’ve treated patients with this agent who have relapsed and refractory HL and I saw patients with very advanced disease with multiple prior therapies—up to 14 prior lines of therapy—all of whom responded and are doing great with very little toxicity. I think it’s absolutely amazing. It’s not a home run, it’s a grand slam. You know—the ninth inning of the World Series with two outs, no runners on base, or bases loaded—whatever analogy you’d like to use.
Do you think that these agents will ultimately prove useful in all hematologic malignancies or does the data so far suggest that it is likely to be limited to certain types?