How Classification of Lymphoma in the Modern Era Impacted Patient Treatment, Patient Care

Pharmacy Times interviewed Elaine Jaffe, MD, National Institutes of Health (NIH) distinguished investigator at the National Cancer Institute (NCI) at NIH, who is receiving the American Society for Investigative Pathology Gold-Headed Cane Award and is presenting an award lecture at the Experimental Biology 2022 conference on the classification of lymphoma in the modern era—a marriage of pathology and genomics.

Question: How has classification of lymphoma in the modern era impacted patient treatment and patient care opportunities?

Elaine Jaffe: So, I think as we identify the molecular pathogenesis, this has helped us to develop targeted therapies. So, speaking about some of the histiocytoses, which I mentioned earlier, a recognition of the genetic alteration can lead to targeted therapy.

So we now have [anaplastic lymphoma kinase (ALK)] inhibitors that can be used to treat ALK-positive histiocytosis, BRAF inhibitors that can treat Langerhans cell histiocytosis, and other specific drugs that can target different components of the pathway of these neoplasms.

In addition, for lymphomas, for example, we used to lump all diffuse large B-cell lymphomas together. Now, we recognize the so-called activated B-cell subtype of diffuse large B-cell lymphoma and the germinal center-derived subtype of large B-cell cell lymphoma.

In fact, greater complexity is emerging. We know that some of the drugs that we use to treat diffuse large B cell lymphoma, such as the [Bruton’s tyrosine kinase (BTK)] inhibitors, are much more effective in tumors of the activated B-cell subtype, the ABC subtype, than the germinal center B-cell subtype. So, this is really influencing drug development and new therapeutic approaches.

Question: Where do you see the classification of lymphoma progressing in the coming years?

Elaine Jaffe: Well, I think we’ll see continued evolution with greater integration of sequencing methodologies that will be introduced into the clinical setting. Most routine laboratories do not have [next-generation sequencing (NGS)] technology widely available, but I think this will become a much more standardized approach to diagnosis for lymphomas and leukemias.

Question: What are your hopes for the future of lymphoma classification?

Elaine Jaffe: Well, I mean, I think we’ll continue to show progress in understanding individual disease entities and development of targeted therapy. When I started in pathology, there were only 4 subtypes of lymphoma: lymphoma sarcoma, reticulum cell sarcoma, giant follicular lymphoma, and Hodgkin’s lymphoma. Today, we have more than 100 subtypes.

Some of the new therapeutic programs that are being developed are developed to target particular pathways. For example, at the NCI, we have a regimen called [venetoclax, ibrutinib, prednisone, obinutuzumab, and Revlimid (ViPOR)] that’s now in testing, and it was really developed to target key pathways in lymphoma development. So, it includes venetoclax—which is a BCL-2 inhibitor, BTK inhibitors, and inhibitors of NF-κB survival pathways. So I think that this will be a continued approach in the future.