Dr. Nina Shah, associate professor in the Department of Medicine at University of California San Francisco, discusses how CAR T-cell therapy may further transform the treatment of relapsed/refractory multiple myeloma and how researchers are looking to optimize these treatments for this still incurable blood cancer.

What may CAR T-cell therapies offer patients with relapsed/refractory multiple myeloma?

“The hope is that CAR T-cell therapy may be a way for some patients with relapsed/refractory multiple myeloma to have a chance for a long-lasting treatment response. Clinical trials are still in the early stages.

Currently, multiple myeloma is treated with several repeated cycles of different therapies. Patients would most likely still go through these treatment regimens before receiving CAR T in a later line of therapy, but it would be one of the few single agent treatments these patients would receive.”

Will CAR T-cell therapy be as effective in multiple myeloma treatment as it has been in other blood cancers?

“It remains to be seen. Every tumor has different properties. So it will depend on many factors, including whether targeting BCMA kills the cells that drive the cancer and whether the CAR T-cells themselves disappear or stick around.

As we continue to see follow up research, we’ll look at the longevity of these CAR T-cells as well as the duration of the response. Will finding these CAR T-cells in patients long after treatment correlate with efficacy and survival? If so, we would try to use that information to create T-cells that last longer in patients.”

What is the toxicity profile of CAR T in multiple myeloma?

“In clinical trials, patients with multiple myeloma have tolerated CAR T-cell therapy as anticipated, but further investigation is needed. We can’t compare across disease states as patients themselves may experience the treatments differently in some ways. While it is uncertain why, what we do know is that as toxicities and disease states are better understood, along with further optimization of dosing, we may be in a better position to manage these responses. We have also learned from our colleagues who have been using CAR T-cell therapy for longer in cancers such as in leukemia and lymphoma.”

How would you characterize the early results in multiple myeloma?

“CAR T-cell therapy research offers hope for patients with relapsed multiple myeloma who have already been through several lines of treatment. But we shouldn’t be overzealous.

In general, we have to work harder to understand why not all patients respond and which patients are most likely to receive a benefit from CAR T-cell therapy. If we can predict that and learn why others don’t benefit and why relapses occur, then maybe we can improve how we engineer CAR T-cells.”

Could CAR T-cell therapy be combined with other treatments for multiple myeloma?

“There may be the potential for combinations worthy of investigation as we look toward the future with therapies such as immunomodulatory regimens and checkpoint inhibitors. Moreover, further exploration of CAR T-cell therapies given simultaneously with other agents may show the potential to boost their activity. In any case, such combinations would require additional studies and careful attention should always be given toward the potential toxicities that may occur in combination strategies due to T-cell overreaction.”

What other ways could researchers optimize CAR T-cell therapy?

“We see lots of creativity in how we design these therapies. Some researchers are trying to grow CAR T-cells under conditions that would allow them to last longer once they are given back to the patients, and others are trying to add an on/off switch to CAR T-cells, so they only activate when they encounter signs of a tumor.

Meanwhile, we’re looking at when we use these therapies. Right now, CAR T-cell therapies are being studied in patients who have tried and relapsed on multiple treatments. Using it sooner might be useful for patients with high-risk disease who don’t have very durable responses to traditional treatments, but this will require additional research. So I’m looking forward to seeing the results of clinical trials as we learn more about CAR T-cell therapies in the multiple myeloma field.”