“There is a group of patients that is refractory, where the disease either doesn’t go away with conventional therapy or comes right back as soon as you stop the conventional therapy, and another group of patients who enjoy months or a few years before comes back and then they relapse. It is not clear what the path forward should be, how best to help those patients.”

As the RHL30 study noted, “the current standard of care for young, fit patients who experience refractory or relapsed disease is salvage chemotherapy followed by high-dose chemotherapy and autologous stem-cell transplantation (ASCT).”

But, the authors added, the outlook for those patients is bleak. “Approximately 50% of patients are not cured by such therapy and eventually die as a result of the disease.”

The reasons why, and how to identify which patients may or may not benefit from transplantation, remain unclear.

“We have for a long time thought of cancer as a kind of a monolithic entity; it’s a clonal proliferation of cells to the exclusion of all else,” said Dr Klein. “But it turns out that cancer is far more complicated, and that cancer exists within an environment in the body and it’s not blind to this environment. It actually interacts with the environment and there are features about the environment that help to sustain the cancer. The cancer sort of manipulates its environment and is also influenced by its environment.”

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Predictors of poor outcome for patients whose lymphoma recurs include time to relapse after initial therapy, advanced stage at relapse, and poor performance status.4

“I think the challenge that we’re facing right now is that we have a lot of prognostic factors, but we don’t have a lot of predictive factors,” Dr Klein said. “We know, for example, in this study with Hodgkin lymphoma, that if you have the poor risk gene signature you’re going to do poorly despite transplant. The problem is it doesn’t tell us what else we should be doing. And that’s really the challenge.”

Dr Steidl agreed that finding identifiable relapse biomarkers is only a first step.

“Prognostic means yes, you have the knowledge, but there’s nothing you can do about it. We want to go beyond that,” he said. “Actionability comes into play when you have a biomarker that offers alternatives.”

The RHL30 study, he said, served as proof of concept.

“What now has to be done,” he said, “is we have to formally show clinical utility. Clinical utility is tied to decision-making, obviously, about picking the right treatment option.

“That is something that has to be shown in the next generation of clinical trials.”

Still, a biomarker prognostic tool such as RHL30, the study’s authors concluded, meshes perfectly with the growing arsenal of increasingly personalized therapies, including checkpoint inhibitors and new immunotherapies targeting CD30 in relapsed and refractory Hodgkin lymphoma cases.

“For these high-risk patients,” the study’s authors concluded, “the development of biomarkers at relapse, such as RHL30, comes at a timely juncture in the field, because recent studies have demonstrated the efficacy of novel therapies such as BV (brentuximab vedotin) and PD-1 blockade.”

References

  1. Chan FC, Mottok A, Gerrie AS, et al. Prognostic model to predict post-autologous stem-cell transplantation outcomes in classical Hodgkin lymphoma. J Clin Oncol. 2017 Sep 12. doi: 10.1200/JCO.2017.72.7925 [Epub ahead of print]
  2. What are the key statistics about Hodgkin lymphoma? American Cancer Society website. https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed September 2017.
  3. Survival rates for Hodgkin lymphoma by stage. American Cancer Society website. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed September 2017.
  4. Kuruvilla J, Keating A, Crump M. How I treat relapsed and refractory Hodgkin lymphoma. Blood. 2011;117(16):4208-17. doi: 10.1182/blood-2010-09-288373