Easing the Side Effects of Immunotherapy

A flurry of new therapies for multiple myeloma, the second-most common type of blood cancer, has recently entered the clinic. As physicians onboard the new drugs, they are learning how to manage the side effects that sometimes accompany them.

One new drug, the immunotherapy teclistamab, can lead to a potentially deadly side effect called cytokine release syndrome (CRS). Physicians monitor patients in the hospital when they first receive the drug and treat patients for CRS if they begin to show symptoms such as fever and low blood pressure.

Acting to Prevent CRS

A new study aims to nip CRS in the bud before it starts. The findings show that providing CRS treatment prophylactically, prior to teclistamab administration, appears to slash the rate of CRS in multiple myeloma patients.

If supported by additional data, the findings could lead to the elimination of hospital stays for patients taking teclistamab or other immunotherapies, and broaden access to treatment.

“In an ideal world, you could pre-medicate patients against CRS and treat them in an outpatient setting,” said study leader C. Ola Landgren, M.D., Ph.D., chief of the Division of Myeloma at Sylvester Comprehensive Cancer Center, part of UHealth—University of Miami Health System. “There is huge interest in this worldwide.”

Blood Cancer Discovery, a journal of the American Association for Cancer Research, published the study Jan. 4.

New Drugs, New Side Effects

Teclistamab is a bispecific T-cell engager, a class of drugs that binds both a target on tumor cells and a target on T cells. The therapy activates T cells to attack the tumor.

The result is tumor shrinkage. In a key clinical study, teclistamab yielded an overall response rate of 63% in multiple myeloma patients whose tumors failed to respond or became resistant to multiple previous therapies. Teclistamab was approved for such patients in 2022, followed by two other bispecific T-cell engagers.

Immunotherapies like teclistamab work by bumping up the immune response against the tumor. But this activity can lead to overactive immune activity, the hallmark of CRS.

Physicians often treat CRS with drugs that counteract specific cytokines (immune molecules that cause T cells to go into overdrive). One such drug, tociluzumab, has been used for years to quell CRS caused by various immunotherapies.  

In case they need such treatment, patients receiving teclistamab typically stay in the hospital five to seven days for monitoring.

Some patients forgo immunotherapy because of the long stays.

“It’s a big barrier,” said Dr. Landgren.

Promising Results for Multiple Myeloma Patients

Dr. Landgren and his colleagues initiated their research after seeing preliminary data in 2022 on multiple myeloma patients treated with prophylactic tociluzumab. The approach seemed to ease CRS in patients receiving an experimental, bispecific T-cell engager that binds a different target on cancer cells than teclistamab.

Dr. Landgren then decided to move “full speed forward” with testing the approach at Sylvester in patients receiving teclistamab.

He and his colleagues now reveal the outcome in 31 multiple myeloma patients, showing that only 13% developed CRS when treated prophylactically with tocilizumab. That’s compared to the 72% observed in a key earlier study that treated patients for CRS as symptoms arose. In addition, the Sylvester patients had less severe CRS and lower rates of CRS recurrence.

The approach also seemed to ease a second, less-common side effect called ICANS (immune effector cell-associated neurotoxicity syndrome).

Prophylactic tocilizumab treatment of multiple myeloma patients receiving bispecific T-cell engagers is now standard-of-care at Sylvester and a handful of other cancer centers. Dr. Landgren and his colleagues continue to monitor outcomes in such patients.

“We are ahead of the curve,” he said.

The Sylvester findings are consistent with emerging data from a separate study of multiple myeloma patients treated prophylactically with tocilizumab. Similarly, patients receiving CAR T-cell immunotherapy also seem to benefit from prophylactic CRS treatment.

Future Treatments for Cancer

Questions under study include whether prophylactic treatment for CRS puts a dent in the effectiveness of teclistamab or other drugs in the class. So far, the answer appears to be no, said Andrew Kowalski, PharmD, BCOP, a hematology/oncology clinical pharmacist at Sylvester and the study’s lead author.

As they test new patients, Sylvester researchers also prepare for the future. They are quietly readying an outpatient service to deliver teclistamab and other bispecific T-cell engagers, anticipating that U.S. regulators may lift the requirement for hospital stays.

“This approach has the potential to be expanded into other leukemias and lymphomas, as well,” added Dr. Kowalksi.

Dr. Landgren recalls that more than 20 years ago, patients treated with the then-new drug rituximab required monitoring in the intensive care unit. Now, physicians know how to manage potential side effects and the drug is available without a hospital stay.

Dr. Landgren anticipates a similar evolution toward outpatient treatment for patients receiving teclistamab and other emerging immunotherapies.

“The field of myeloma is probably one of the biggest examples of successful drug development in modern times,” said Dr. Landgren. “We are going with full steam into an era of immunotherapy.”

Tags: CAR T cells, Dr. C. Ola Landgren, immunotherapy, multiple myeloma, Sylvester Comprehensive Cancer Center