Emerging BCMA-directed CAR T-Cell Therapies in RRMM - Episode 1

Progress in the Treatment of R/R Myeloma

Nikhil C. Munshi, MD:Welcome to thisTargeted Oncology™ presentation on emerging BCMA [B-cell maturation antigen]—directed CAR [chimeric antigen receptor] T-cell therapies in relapsed/refractory multiple myeloma.

I am Dr Nikhil Munshi, director of basic and correlative science at the Jerome Lipper Multiple Myeloma Center [and LeBow Institute for Myeloma Therapeutics at Dana-Farber Cancer Institute], as well as senior physician and professor of medicine at Harvard Medical School in Boston, Massachusetts.

Joining me today is my colleague Dr Parameswaran Hari, professor of medicine and chief of the Division of Hematology/Oncology of the Medical College of Wisconsin in Milwaukee.

Recent research and drug development in the multiple myeloma field has started to shift this once fatal cancer into a chronic disease, with overall survival of 10 years to 20 years. As drugs are developed, we are learning how to use them in specific patient populations to improve outcomes and make a larger impact on an individual’s life. Today we are going to talk about emerging CAR T-cell strategies in patients with relapsed/refractory multiple myeloma and will review recent data from the ASH [American Society of Hematology] 2019 meeting.

Thank you for joining us; let’s begin.

Dr Hari, welcome. Today we are discussing the changing landscape of the treatment of relapsed/refractory myeloma. With all of these new drugs becoming available and being approved, can you tell me what you think is changing in this field?

Parameswaran Hari, MD, MRCP:It’s a pleasure to be with you, Dr Munshi. As you are aware, relapse is a problem in myeloma. Unfortunately, all of our patients eventually relapse and become refractory to anything that we can offer them. Almost everyone with myeloma has that fate. In this context, it is exciting that we have several classes of drugs, including a drug class that has been approved in 2019, with selinexor. And we have, as reviewed at this ASH meeting, several classes of drugs that are targeting the BCMA pathway. And then there is more to come with the results of phase I trials that are coming out. As we very well know, the landscape is changing, as we get a new class of action and new agents belonging to a different class of drugs.

Nikhil C. Munshi, MD:So with all of the drugs that we have, we have 3 proteasome inhibitors: bortezomib, carfilzomib, and ixazomib. We have 3 immunomodulators: thalidomide, lenalidomide, and pomalidomide. And then we have 2 antibodies: daratumumab [and] elotuzumab. We have an HDAC inhibitor called panobinostat. We have selinexor as a new class of agents. So which one of those do you think would be useful as a later line of treatment?Also, the question comes up: 2-drug, 3-drug combinations? And we can also combine the old drug with the new drug, Cytoxan [cyclophosphamide], melphalan, bendamustine. Which one do you think is appropriate as the later line of treatment? And what would, in your opinion, be more useful for the later lines of treatment?

Parameswaran Hari, MD, MRCP:Yeah. You summarized this very well. We have traditional cytotoxic and the whole area of new agents that have changed the landscape. Unfortunately, most people who are in need of treatment in the fourth line and beyond are patients who have already been exposed to all 3 of the major classes. You and others have worked in this landscape and have found that these patients are clonally multiply evolved. Their genetics are significantly different. You have agents that produce responses in them, but these responses are often not sustained. We usually go back to triplet combinations or quadruplet combinations in a desperate effort to control disease in these patients. Selinexor does open up a pathway, but we haven’t identified the best partners to work with selinexor yet. And as you know, it’s approved as single therapy or with steroids. Once we get more drugs to combine with selinexor, we may have even better results.

Transcript edited for clarity.