Wasif M. Saif, MD, deputy physician-in-chief and medical director at Northwell Health Cancer Institute in Lake Success, New York, who was not involved in the study, said the toxicity profile shown in the study was “acceptable.” Dr Saif added, “This study warrants a randomized study to confirm the benefit of pembrolizumab in improving PFS in this high-risk patient population.”

Stephen Ansell, MD, PhD, a professor of medicine at the Mayo Clinic in Rochester, Minnesota, who was not involved in the new research, said that the new findings were important. “In general, the goal of all therapies that we’re doing to Hodgkin lymphoma patients is to try and do our best to get patients in remission and have them stay there,” he said. “[The researchers] gave pembrolizumab every 3 weeks after the person had recovered from the transplant as a strategy to keep the disease under good control, and their goal was to improve the outcomes by 20%, which I think most people feel is very relevant.”

Dr Ansell noted that other investigators have done related research in patients with Hodgkin lymphoma at high risk of progression or relapse.

For example, results from the phase 3 AETHERA trial published in 2018 in the journal Blood found that administering brentuximab vedotin (BV) to patients with the condition after autologous hematopoietic stem cell transplantation improved PFS.5 In that study, which involved nearly 330 patients, the authors administered BV 1.8 mg/kg to half of the patients and placebo to the other half, for up to 16 cycles beginning about a month following transplantation. At 5-year follow-up, PFS among the patients who received the BV treatment was 59%, compared with 41% among the patients who received placebo.

The lasting improvement in PFS found in the AETHERA study indicates that the treatment approach used in the study might actually improve the cure rate of autologous transplants, wrote the authors of the 2019 study of pembrolizumab.3 “This suggests more generally that treatments, which by themselves may not have strong curative potential in advanced [relapsed or refractory] disease can, in the context of ASCT, be delivered with curative intent,” they wrote.

More research is needed to examine and understand the mechanisms of such treatments’ curative potential following autologous transplantation. One possibility is that, after an autologous transplant, “there is a lot less tumor around,” Dr Armand said. “And it may be easier to eradicate a very small amount of tumor than a large amount of tumor.”

Moreover, as Dr Ansell put it, the transplant ends up “rebooting” the immune system after fighting the disease. “And if you can optimize the immune system as it kicks back in, that may actually provide a better outcome long term,” Dr Ansell said. “My hope is that not only will it be progression-free survival that’s improved, but actually overall survival.”

References

  1. Hoppe RT, Advani RH, Ai WZ, et al. NCCN Guidelines Insights: Hodgkin Lymphoma, Version 1.2018. J Natl Compr Canc Netw. 2018;16(3):245-254.
  2. Smith SD, Moskowitz CH, Dean R, et al. Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres. Br J Haematol. 2011;153(3):358-363.
  3. Armand P, Chen YB, Redd RA, et al. PD-1 Blockade with Pembrolizumab for Classical Hodgkin Lymphoma after Autologous Stem Cell Transplantation [published online April 5, 2019]. Blood.
  4.  US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
  5. Moskowitz CH, Walewski J, Nademanee A, et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018;132(25):2639-2642.