Exclusive Q&A with Dr. Hearn Jay Cho, Mt. Sinai Hospital, NY, NY

Ravi Vij

Cancer Research Institute Initiative
A promising avenue of clinical research in multiple myeloma is the use of immune checkpoint inhibitors. As most myeloma patients know, there is a constant need for multiple agents, with new mechanisms of actions to treat relapsed and refractory patients.

Q) Why is this initiative important to patients?

A) Immune therapy is one of the most important, recent developments in cancer treatment. The majority of progress has been in solid tumors, but we are getting the first results showing that it can also be effective in blood cancers such as Hodgkin’s lymphoma and multiple myeloma. The CRI was an early and steadfast champion for cancer immunotherapy, in much the same way as MMRF is a champion for myeloma research. This initiative brings together the expertise and support for both cancer immunotherapy and multiple myeloma to accelerate clinical trials.

Q) What patient population will benefit and why?

A) The first clinical trial of this initiative will investigate the use of tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-L1) immune checkpoint inhibitors to boost the effectiveness of autologous stem cell transplantation. We believe that transplant is a great place to investigate immune therapy, given the zero presence of myeloma cells and fresh immune cells after auto-transplant provides the best opportunity to mobilize effective anti-myeloma immunity and eradicate tumor cells. There are many ongoing clinical trials applying immune therapy in smoldering, newly diagnosed, post-transplant, and relapsed disease. We have already seen the fruits of these efforts with the approval of daratumumab (anti-CD38) and elotuzumab (anti-SLAMF7) targeting antibodies for myeloma, and we hope this is just the beginning.

Q) If patients do not participate, how does the study benefit them?

A) We believe that current clinical trials will lead to FDA approval for myeloma of one or more of this particular class of immunotherapy agents, immune checkpoint inhibitors, in the near future. These trials will provide new and effective agents for future use in the general myeloma community.

Q) Why have immune therapies such as these generated so much excitement in the field?

A) Immune therapies are important for two reasons. First, they have proven that the immune system can recognize and kill cancer cells. This was a concept that has been debated for more than a century, and now the success of treatments like the immune checkpoint inhibitors has settled that question. Second, these agents are effective even in advanced disease such as stage IV melanoma, bringing hope to patients in situations where historically there were very few options and poor prognosis.

Q) What makes treatment with immune therapies different than other existing treatments?

A) Immunotherapy is fundamentally different from chemotherapy, in that they are not necessarily designed to directly kill tumor cells with chemical toxins. instead, they mobilize the patient’s immune system to fight cancer, similar to how it fights infections. In the best case scenario, there will be a very high level of specificity for killing cancer cells. In addition, immunologic memory can theoretically provide long-lasting control of disease. There can be side effects from immune activity against normal tissue, so it is not completely risk-free, but in most cases these can be managed. Immune checkpoint inhibitors can also be combined with other immunotherapies such as the targeting antibodies mentioned earlier, and with immune modulating drugs such as Revlimid or Pomalyst, raising the possibility of combination immunotherapy improving or replacing conventional chemotherapy.