Multiple myeloma has long vexed medical researchers because of the cancer’s specific ability to both weaken and “hide” from a patient’s own immune system. The result is that while many treatments have been able to treat the disease for some time, patients subsequently relapse.
But newer medications now can control the disease for extended lengths of time. “We want to turn this into a chronic disease we can manage with minimal side effects,” says Washington University hematologist/oncologist Michael Slade, MD. “We are particularly excited about two novel immunotherapies, CAR T-cells and bispecific antibodies.”
CAR T-Cells
CAR T-cells are a re-engineered version of a patient’s own T-cells that are modified to attack the cancer. Currently, the U.S. Food and Drug Administration has approved two CAR T-cell therapies for adult patients with relapsed and refractory multiple myeloma. The two, Abecma and Carvykty, both target the B-cell maturation antigen (BCMA), a cell surface protein found in almost all cases of multiple myeloma.
“Patients who receive approved CAR T-cell therapy are those who have relapsed after receiving several other courses of treatment,” notes Slade. “But results have been promising and we now have open clinical trials that are investigating whether we can have better, longer responses if we give CAR T-cell therapy earlier in the disease process and before patients have multiple failed therapies.”
Physicians at Siteman Cancer Center at Barnes-Jewish Hospital and Washington Unviersity School of Medicine have long-standing expertise in CAR T-cell therapy research and clinical care. Early clinical trials for the two multiple myeloma therapies were offered here and research helped lead to FDA approval.
Bispecific Antibodies
Bispecific antibodies are another area of rapid development. These stick to two different proteins at the same time, linking attacking T-cells directly to cancer cells. The advantage of these therapies is that they are universal, off-the-shelf treatment options.
“CAR T-cell therapies are customized therapies. We must retrieve T-cells from the patient, send them for manufacturing in a lab, and then infuse them back into the patient, all of which can take weeks,” explains Slade. “With bispecific antibodies, we can treat a patient in days.”
Already, one bispecific antibody, Tecvayli, has been FDA-approved for the treatment of relapsed, refractory multiple myeloma in patients who have previously received four other lines of therapy. Tecvayli targets both BCMA and CD3 antigens and clinical trials showed it had an overall response rate of more than 60 percent among study participants. Multiple other bispecific antibodies have shown promise in clinical trials and are expected to be approved within the next several years.
Slade says patient fitness is one factor that determines whether CAR T-cell therapies or a bispecific antibody is the best choice. “CAR T-cell therapy is more intensive and requires one to two weeks of hospitalization for the infusion and close monitoring for about a month,” he says. “But patients have experienced long durations of remission and can often go off therapy completely for quite a long time. Bi-specifics can be less toxic but require more doctor visits because they are given by infusion every one to four weeks.”
As with CAR T-cell therapy, newer clinical trials are under way to start bispecific antibody treatments earlier in the disease process. “The key is for physicians to think about clinical trials at every stage of the disease journey, from diagnosis onwards,” stresses Slade. “Treatments are becoming more effective, and remissions are lasting longer. Our goal is to keep patients ahead of the drug development curve and keep them alive, healthy, and eligible for the latest therapy until a cure for myeloma can be developed.”
To view the list of active clinical trials at Siteman, go to siteman.wustl.edu/clinical-trials.