Bridging Global Treatment Gaps in Relapsed Multiple Myeloma

Multiple myeloma remains an incurable disease, so the principal goal of therapies is to extend progression-free survival. But challenges remain in the length of the manufacturing process and being able to bring the benefit of chimeric antigen receptor (CAR) T-cell therapies to patients around the world, explains Leland Metheny, MD, lead investigator for the phase 1 BAFF CAR T clinical trial, University Hospitals Seidman Cancer Center.

In part 3 of our interview, Metheny, who is also hematologist-oncologist at University Hospitals and assistant professor of medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, addresses the how he hopes cell therapy will revolutionize cancer care.

This transcript has been lightly edited.

Transcript

What treatment gaps in RRMM does triple-target CAR T-cell therapy address?

Multiple myeloma is a blood cancer. It's generally thought to be incurable, so the focus of therapies for multiple myeloma involve extending progression-free survival. They are not necessarily focused on cure. There's a few nuances or caveats there, but in general, that's the focus of most immune/chemo/cellular therapies in in multiple myeloma.

The patients who go to CAR T-cell therapy already have seen or a large number of therapies that are chemotherapy or immunotherapy, and when they go to FDA-approved CAR T-cell therapy, it's not expected those patients to have a cure. They will eventually and ultimately relapse from their disease. So how can we improve upon the existing CAR T-cell therapies for multiple myeloma and extend that progression-free survival longer than a year or a little bit over a year, which is kind of the standard of expected progression-free survival in those patients.

It's making more effective CAR T-cell therapies that expand the progression-free survival. Second, some of these CAR T-cell therapies that are FDA approved do take a little bit longer to manufacture, and sometimes people can't wait a month or plus to get their CAR T cells. So the manufacturing process that we have is actually shorter. It can actually happen within 14 to 16 days, which for some people, that makes a big difference. That extra 2 weeks can be life saving for many patients. And then thirdly, is what I kind of discussed previously, is finding CAR T cells or generating CAR T cells that do not allow cancer cells to escape the effectivity of those CAR T cells.

What are the long-term goals of this research, and how does this therapy fit into the broader treatment landscape of RRMM?

Long-term goals for cell therapy in general progress through multiple phases. Phase 1 is determining safety, but our ultimate goal in any cell therapy is to bring it to patients in clinics throughout the world, obviously. So we want it to be safe and to be effective. That's kind of the ultimate goal: getting it at a standard-of-practice therapy for patients, given that it's safe and effective.

Cell therapy is going to revolutionize cancer care whether or not it's going to be solid tumor or liquid tumor. It will help revolutionize autoimmune diseases, and it will start moving earlier up the treatment lines, because it is such an effective therapy. What that means is, is instead of somebody having to go through 2, 3, 4, 5 different types of chemotherapy that can really wreck your body, cell therapies will be brought after first line therapy to affect either a cure or a very long progression-free survival for our patients who have liquid or hematologic malignancies or solid tumors. So that's kind of the goal, I think, of anyone who's dealing with cell therapies right now: to bring it to make sure it's safe, effective, and bring it up earlier on the treatment lines to improve the lives of all our patients.

One of the things that's important to recognize in cell therapies is something I alluded to in the past, is kind of the manufacturing process and the logistical hurdles that lots of us face in the developed world. Now, you can imagine what the hurdles and logistical problems are in the near-developed world or underdeveloped parts of the world, and so there's a real kind of disparity between what's available for people in a resource-rich environment and those in not so much of a research-rich environment. And what we call point-of-care CAR T-cell manufacturing, where the car T cells can be manufactured close to the place that's getting or that's receiving the cell therapy, and they can be manufactured simply and efficiently and fast, is another kind of thing that we're focused on at University Hospitals.

We have point-of-care CAR T cells, lots of people have point of care. But then translating that to places in the near-developed or resource-poor areas of the world, so that not just Americans or Canadians or Europeans can get these cell therapies, but everyone is allowed the benefit of the science and the research that we're doing.