Lost in Translation: The Critical Need for CRS Awareness in Talquetamab Therapy

Introduction/Background/Significance: Multiple Myeloma (MM) is an abnormal growth of plasma cells in the bone marrow and remains a major contributor to mortality. The current treatments for MM include proteasome inhibitors, immunomodulating drugs, anti-CD38 monoclonal antibodies and bone marrow transplant (BMT). Even with these modalities, MM can recur, for which new therapies such as chimeric antigen receptor T cell (CAR-T) and bispecific antibodies (BsAbs) were developed. Talquetamab is a novel BsAbs that binds the G-protein-coupled receptor in MM plasma cells and has induced remission of MM in patients that have failed at least four prior lines of therapy. In this case report, we present a patient with refractory MM who received Talquetamab.

Materials and Methods/Case Presentation/Objective: This is the case of 56-year-old male with recurrent metastatic MM who failed multiple lines of therapy, including a BMT in 2021 and CAR-T. He came to the ED due to progressive weakness, fevers, multiple tender palpable masses and violaceous nodular lesions throughout his body. Abdominal CT scan and PET/CT reported extensive lymphadenopathy and innumerable hypermetabolic lesions, suggesting progression of MM. His initial laboratory work up was remarkable for anemia, thrombocytopenia and mild transaminitis. A new BM biopsy revealed persistent plasma cell proliferative disorder. Based on these results, the patient was started on Talquetamab as a last line of therapy. The first three step-up doses were tolerated with expected complications, such as tumor lysis syndrome and anemia. On day 10 of therapy, the patient received his first full dose of Talquetamab, which resulted in hypotension refractory to fluids and respiratory distress requiring O2 supplementation. Due to his worsening condition, he was transferred to the Intensive Care Unit (ICU) for low-dose vasopressor support and mechanical ventilation. Despite these supportive measures, the patient developed kidney and liver failure. After a discussion with the patient's wife, she decided that there would be no escalation of therapy. The patient was placed on hospice care and made DNR; he passed away the next day.

Results/Description/Main Outcome Measure(s)

According to the MonumenTAL-1 trial, Talquetamab causes cytokine release syndrome (CRS), a rare but known adverse effect (AE) where circulating cytokines, mainly IL-6, cause multi-organ damage with severity divided into four grades. All CRS grades require supportive care, with grades 3 and 4 warranting an IL-6R antagonist and steroids. Without proper guidance, a new medical team may misinterpret a refractory MM patient's poor prognosis and overlook the benefits of CRS treatment. Unfortunately, IL-6R antagonist was not administered because the patient's wife, possibly unaware that CRS can be treated independently of overall prognosis, opted against further intervention. This underscores the vital need for clear communication with both the patient's family and other medical specialties. Additionally, the primary team must reinforce to the ICU staff that, despite the patient's poor prognosis, supportive measures are still essential.

Conclusions: Talquetamab is a novel therapy for patients who have failed multiple MM treatments, and its most common AE is CRS. Although the clinical picture of CRS might seem catastrophic, it is vital provide all necessary supportive measures until symptoms subside, regardless of patient prognosis.