Hodgkin Lymphoma: Assay May Predict Post-transplantation Relapse, Possibly Guiding Non-transplant Options

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The gene expression-based prognostic model, RHL30, has the potential to provide insights for the selection of treatment strategies catered to the individual patient.
The gene expression-based prognostic model, RHL30, has the potential to provide insights for the selection of treatment strategies catered to the individual patient.

A new and novel genetic assay offers the possibility of predicting autologous stem cell transplantation (ASCT) outcomes for patients with relapsed classical Hodgkin lymphoma, according to its developers.

Perhaps even more importantly, the authors of a new study wrote, the gene expression-based prognostic model dubbed RHL30 has the potential to provide powerful insights for the selection of treatment strategies catered to the individual patient.1

“The prognostic power of RHL30 might be of important translational relevance for future clinical trials and patient management,” they wrote. “Such prognostic information can provide the foundation for informed clinical decision-making supporting the use of ASCT as a second-line regimen in low-risk patients or suggesting that alternative therapeutic approaches should be considered in high-risk patients.”

One of the study's key findings, said corresponding author Christian Steidl, MD, research director at the BC Cancer Agency's Centre for Lymphoid Cancer in Vancouver, Canada, was confirming biological differences between tumor specimens taken at initial presentation and at relapse.

“What we for sure can say is that there is a dynamic aspect. There is a difference between relapse and initial diagnosis,” Dr Steidl said. “A next step is to decipher how the biological difference between relapse and initial diagnosis comes about.”

The differences, the study stated, could be linked to changes in the tumor's microenvironment (TME) caused by chemotherapy such as doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent therapy.

“We provide evidence for biologic divergence, suggesting that chemotherapy, such as ABVD, induces selective pressures resulting in tumor/TME evolution.”

Most significantly, they said: “We show that the biology at relapse, compared with primary diagnosis, provides superior prognostic information for predicting treatment outcomes after ASCT.”

The specific tool they created was derived from probes of an initial code set of 784 endogenous and 15 housekeeper genes, using the NanoString platform to perform digital gene expression profiling on 200 ng of RNA.

Comparing the immunohistochemistry of relapse specimens with corresponding gene expression data revealed a strong correlation between CD20, CD68, and CD163 proteins and mRNA expression.

Eventually, the study's authors wrote, they constructed a prognostic model “consisting of 18 outcome-associated and 12 housekeeping genes” including “B-cell, macrophage, HRS-cell, neutrophil, and natural killer–cell components, as well as a drug resistance component.”

RHL30, they stated, “identifies a low-risk group of patients who have excellent survival rates when treated with the current standard of care and a sizable group of patients who frequently experience second-line treatment failure.”

According to the American Cancer Society, “classic Hodgkin lymphoma accounts for about 95% of all cases of Hodgkin lymphomas in developed countries.”2

It is also considered highly treatable, with 5-year survival rates at about 86%, and 10-year survival rates close to 80%. Even advanced-stage cases at initial diagnosis have 5-year survival rates of around 65%.3

“We've got very effective therapy. We're going to cure 85% of patients with Hodgkin lymphoma,” said Andreas Klein, MD, director of the Hematologic Malignancies Program and assistant director of the Bone Marrow and Hematopoietic Cell Transplant Program at Tufts Medical Center in Boston, Massachusetts.

But, he continued, “what about that other 15% of patients who unfortunately follow a different trajectory? We don't have a great way of identifying who those people are going to be from the beginning.

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