Immunotherapy Modalities Are Here to Stay

The Society of Hematologic Oncology (SOHO) is a dedicated group of academicians, clinicians, research scientists, and related specialists who are committed to advancing efforts in the research and treatment of hematologic malignancies. SOHO’s mission is to expedite worldwide research and education through the exchange of scientific information. We believe that every member of the society plays a valuable role in reaching this goal.

As we congregate this year at the 10th Annual Meeting, let’s remember one of our major functions is to provide an update on the most relevant and recent discoveries. SOHO is an excellent forum in which to learn about the maturity and true value in real life of these discoveries, providing an excellent tool to understand where the treatment—not the research—is heading, and how it incorporates well with existing treatments, which is extremely important for the practicing hematologist.

The Annual Meeting also serves to provide updates to physicians in developing countries who may not routinely have access to this information, and who also appear to be participating in larger numbers in SOHO than ever before.

I chose this year’s theme, “Novel Immunotherapies in Hematologic Malignancies: BiTEs, TRiTEs, and Cellular Therapies,” to highlight the incredible pace at which treatments for hematologic malignancies are advancing. This is really the renaissance of immunotherapy, which is at the forefront in the fight against these diseases.

The progress to date has been remarkable. There are at least four areas that are reaching fruition. The first is the chimeric antigen receptor (CAR) T-cell therapy program.

Several of the CAR-Ts have been already clinically approved. One is the CAR-T directed against CD19. It is approved for treatment of acute lymphoblastic leukemia and is also used in other lymphomas. Another CAR-T, which targets B-cell maturation antigen (BCMA), has been approved for the treatment of myeloma. These treatments have remarkable activity and provide another effective tool in the management of patients.

In parallel, another tool has been developed, and that is bispecific antibodies (BiTEs). BiTEs are reaching fruition, with tremendous numbers of them being developed. Just to mention a few, there are many studies with BCMAs and studies with CD123 in acute leukemia.

A third approach is monoclonal antibodies, which serve as carriers of cargo (such as cellular poisons) and thus become targeted therapies.

Finally, another immunotherapeutic direction is the development of new and existing checkpoint inhibitors. Inhibitors of CTLA-4/CD86 and PD-1/PDL-1 have been approved for the treatment of hematologic malignancies and solid tumors. A whole host of new checkpoint inhibitors, such as TIM-3 and others, are under development. So, there are at least four unique novel immunotherapeutic disciplines that are reaching fruition and playing a major role in treatment of hematologic malignancies.

This immunotherapy renaissance is the culmination of the maturation of the old discoveries combined with new discoveries and new technologies. The clinical application of gene sequencing improved our understanding of the immune system and its targets; consequently, it helped to identify diseases and disease stages that respond better to these therapies.

At the same time, old immunotherapy concepts, such as interferons, are gaining popularity in the treatment of myeloproliferative neoplasia. For instance, pegylated interferon alfa-2b has just been approved for the treatment of polycythemia vera in the United States.

Today, there’s no question that immunotherapy modalities are here to stay and will have a major role in the treatment of advanced cancers. The key question of interest is: Do all tumors respond to the immune system and we simply need to identify more and more targets? Or is it restricted, and we’ve reached the limit? We don’t know, but there is good reason to believe that we are far away from reaching the limits of these modalities.

Moshe Talpaz, MD, is a Professor in the Department of Internal Medicine at the University of Michigan Health’s Rogel Cancer Center and the 2022-2023 President of SOHO.