New cellular therapy offers hope for multiple myeloma patients

Although several effective treatments exist for multiple myeloma, patients with this blood cancer face a disheartening reality: Most will experience relapses over several years, and with each relapse, treatment becomes less effective.

“Nevertheless, we continue to add new drugs and new treatment regimens to push that moment patients run out of options further and further away,” said hematologist-oncologist Andrzej Jakubowiak, MD, PhD, an internationally recognized expert on multiple myeloma who heads a team of University of Chicago Medicine researchers leading the charge to cure the disease.

Patients with multiple myeloma may have no symptoms for years. When the disease is active —for example, at the time a patient first seeks medical help or when the disease is at an advanced stage —they may experience bone pain, fatigue and even confusion, among other symptoms. Because the cancer comes from plasma cells that normally help fight infections by secreting antibodies, multiple myeloma also weakens patients’ immune systems, leading to frequent infections.

Jakubowiak, however, is especially excited about the effectiveness of a new cellular therapy called idecabtagene vicleucel (brand name Abecma.)

“Suddenly we have a tool that completely changes the natural history of the advanced stage of this disease,” he said.

Suddenly we have a tool that completely changes the natural history of the advanced stage of this disease.

In March 2021, the FDA approved Abecma as the first cell-based gene therapy for patients with treatment-resistant multiple myeloma. It works by specifically targeting the BCMA receptor on the surface of myeloma cells. Patients with triple-refractory multiple myeloma who have already undergone four or more therapies, including anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory drug, are eligible and should discuss the treatment with their doctor.

“We were desperate without this treatment,” said Jakubowiak, who directs UChicago Medicine’s multiple myeloma program. “That’s why this type of therapy is a game changer.”

UChicago Medicine was chosen as the first hospital in Chicago to offer Abecma because of its expertise in cellular therapy and strong program for treating multiple myeloma, which includes a multidisciplinary clinic devoted to fast-tracking care for new patients. UChicago Medicine is a member of the Multiple Myeloma Research Consortium, an association of 25 academic hospitals dedicated to bringing promising therapies to patients.

UChicago Medicine multiple myeloma researchers are lead investigators and co-investigators on numerous clinical trials and more recently have used innovative treatment regimens to achieve excellent and durable responses — even among patients with advanced stages of the disease.

“This is why patients should receive cellular therapies at a specialized center,” said Benjamin Derman, MD, a hematologist-oncologist specializing in multiple myeloma. “We’re increasingly achieving impressive responses at any stage of the disease.”

Derman explains that the treatment process with Abecma is similar to the one used to collect stem cells for a transplant but with key differences. Patients are hooked up to a special machine that draws their blood, filters out the T cells, then returns the blood to their body. The T cells are taken to a lab, where over the course of several weeks, they are genetically modified to identify and attack cancerous myeloma cells.

Patients then undergo three days of chemotherapy to knock down any remaining T cells in their body before receiving the modified T cells a few days later. That infusion takes less than 30 minutes.

“In many cases, this is a one-and-done treatment,” said Derman. “This does not require continual treatment and allows for a treatment break.”

Doctors closely watch patients for side effects in the two weeks after the infusion. One possible secondary effect is systemic inflammation called cytokine release syndrome, which is characterized by a fever, fast heartbeat and low blood pressure. Another is neurotoxicity, when certain elements of the nervous system become temporarily impaired. This can present as tremors, confusion and communication problems.

“There are antidotes for many of these side effects,” said Derman. “We can provide this treatment safely and, in most cases, avoid the need for intensive care.”

After receiving Abecma, patients in the karMMa clinical trial experienced longer remission periods, improving from three to four months (using the best previous therapies) to roughly a year; some achieved remission for more than 20 months. And while Abecma is not a cure, Derman said the current pace of innovation in multiple myeloma care suggests new treatments should be available by the time the effects of Abecma wear off.

“We keep working to extend patients’ lives while making sure they feel well,” said Derman. “I think it’s something we do really well at UChicago Medicine.”