Investigators have found that providing prophylactic treatment with the biological agent tocilizumab prior to immunotherapy may reduce the incidence of cytokine-release syndrome in patients with multiple myeloma, according to a study published by Kowalski et al in Blood Cancer Discovery.
Background
Recent advances in treating multiple myeloma—the second most common hematologic malignancy—are providing improved outcomes in patients across the world. Treatment breakthroughs such as the immunotherapy drug teclistamab, known as a bispecific T-cell engager, are designed to bind targets on both tumor cells and T cells to encourage the T cells to attack and ultimately shrink tumors.
A previous study from 2022 demonstrated that teclistamab produced an overall response rate of 63% in patients with multiple myeloma whose tumors did not respond to multiple previous therapies or had become resistant to them. The drug was approved by the U.S. Food and Drug Administration for use in multiple myeloma in 2022, followed by two other bispecific T-cell engagers.
“These immunotherapy drugs work by revving the immune system’s response against the tumor,” explained senior study author C. Ola Landgren, MD, Chief of the Division of Myeloma at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.
However, teclistamab can cause an overactive immune response and may lead to potentially lethal side effects, including cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome.
Because of the potential side effects, patients are required to receive immunotherapies in hospital settings, where they remain for up to 7 days and receive other drugs such as tocilizumab to counteract cytokine-release syndrome and reduce the risk of other treatment-related complications. The required hospital stay may prompt some patients to forgo therapy.
“In an ideal world, you could premedicate patients against cytokine-release syndrome and treat them in an outpatient setting,” emphasized Dr. Landgren. “As a result, there is huge interest in this possibility worldwide,” he added.
Study Methods and Results
In the recent study, the investigators reviewed preliminary data from the 2022 study involving 31 patients with multiple myeloma who were treated prophylactically with tocilizumab.
The investigators discovered that 13% of those who received prophylactic treatment experienced cytokine-release syndrome compared with 72% among patients who participated in an earlier study where they were treated for the syndrome as symptoms arose. Additionally, the patients in this newer study had less severe cytokine-release syndrome and lower rates of recurrence.
The investigators noted that the preventive approach also appeared to ease immune effector cell–associated neurotoxicity syndrome. Similarly, patients receiving chimeric antigen receptor T-cell therapy also seemed to benefit from prophylactic treatment for cytokine-release syndrome.
Conclusions
The investigators hope their new findings may help to eliminate the need to administer teclistamab and other immunotherapies in hospital settings, thereby broadening access to the agents for more patients with cancer.
“Prophylactic treatment with tocilizumab is now standard of care at [the Sylvester Comprehensive Cancer Center] for [patients with] multiple myeloma receiving T-cell engagers,” highlighted lead study author Andrew Kowalski, PharmD, a hematology/oncology clinical pharmacist at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “We are ahead of the curve,” he revealed.
Nonetheless, the investigators listed some questions regarding prophylactic treatment that still remain: Does the new treatment strategy reduce the effectiveness of immunotherapy drugs, and can it benefit patients with other hematologic malignancies? Thus far, the results appeared to be positive. “This preventive approach has the potential to be expanded into leukemias and lymphomas as well,” Dr. Kowalski continued.
The investigators are currently preparing an outpatient service to deliver teclistamab and other emerging immunotherapies in anticipation that U.S. regulators may soon lift the hospital stay requirement. The investigators likened the decision to a previous one involving the cancer drug rituximab—which initially required monitoring in an intensive care unit but now can be administered in an outpatient setting.
“The field of myeloma is probably one of the biggest examples of successful drug development in modern times. We are going with full steam into an era of immunotherapy,” Dr. Landgren concluded.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.
