Pharmacists Lead Advances in Multiple Myeloma Care, New Research Shows
Pharmacists are increasingly vital in the treatment of hematologic malignancies like multiple myeloma (MM), optimizing supportive care, ensuring immunotherapy safety, and guiding therapeutic decisions. Recent findings presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition highlight their expanding roles in infection prevention and managing treatment-related toxicities.
Managing Cytokine Release Syndrome in Talquetamab-Treated Patients
What is Cytokine Release Syndrome?
Cytokine release syndrome (CRS) is an acute inflammatory response triggered by bispecific antibodies (bsAbs), including talquetamab (Talvey; Johnson & Johnson), an FDA-approved treatment for relapsed/refractory multiple myeloma (RRMM). The pivotal MonumenTAL-1 clinical trial (NCT03399799) revealed that up to 80% of patients experienced CRS, predominantly low grade, though some cases reached grade 3 or higher. Current guidelines recommend tocilizumab as a first-line intervention for grade 1 and 2 CRS, with dexamethasone considered as an adjunct, though data on its efficacy and safety remains limited.
Pharmacists are central to managing CRS, including medication dosing and administration, and determining the safest and most effective sequence of agents is crucial for improving patient outcomes. A recent retrospective study, led by Jessica McElwee, PharmD, BCOP, clinical pharmacist coordinator at Atrium Health, examined the safety and efficacy of dexamethasone for CRS management in patients receiving talquetamab, analyzing data from seven academic medical centers.
Data Analysis and Patient Characteristics
The analysis included data from 211 patients with RRMM receiving commercial talquetamab, all of whom received pre-medication and step-up dosing as outlined in the package insert. Patient responses were assessed using criteria from the International Myeloma Working Group (IMWG). Key outcomes included the incidence and severity of CRS events, recurrence, treatment delay, and overall response rate (ORR).
A total of 129 patients (61%) experienced CRS, with 43% experiencing grade 1 and 16% grade 2. Initial interventions varied: 46 patients (36%) received dexamethasone first, 42 (33%) received tocilizumab first, 37 (29%) received supportive care alone, and 4 patients received a combination of both agents.
Dexamethasone vs. Tocilizumab: Effectiveness in Resolving CRS
For patients initially treated with dexamethasone, 11 experienced concurrent immune effector cell-associated neurotoxicity syndrome (ICANS), 33 (72%) had grade 1 CRS, and 11 (24%) had grade 2 CRS. In contrast, among those receiving tocilizumab first, 21 patients (50%) and 20 patients (46%) experienced grade 1 and 2 CRS, respectively.
CRS resolved with a single dose of dexamethasone in 46% of patients receiving it first, with repeat doses needed in 22%, a subsequent tocilizumab dose in 26%, and multiple tocilizumab doses in 4%. For patients initially treated with tocilizumab, CRS resolved with a single dose in 71%, repeat tocilizumab doses in 12%, a single dexamethasone dose in 5%, and repeat dexamethasone doses in 12%.
Impact on Myeloma Therapy
“Like with chimeric antigen receptor (CAR) T-cell therapy, there is that theoretical risk that we could impact the response of our patients by using bispecifics,” McElwee noted. However, at 9.2 months, the overall response rate (ORR) for all patients was 77%, with 50% achieving a very good partial response or better. Importantly, the best ORR was comparable between the dexamethasone and tocilizumab groups (86% vs 90%; P = .74).
“It was encouraging to find that there were no differences in IMWG response rates,” McElwee added. While recurrent CRS was more common in the dexamethasone group, it was generally low grade and manageable. McElwee emphasized that pharmacists should collaborate with patients to determine the most suitable agent, acknowledging that many patients express a preference against dexamethasone due to its side effects. “I find that it’s a very love-hate relationship with dexamethasone,” she explained. “I find that a majority of patients do not prefer to take large quantities of dexamethasone.”
The Role of Live-Attenuated MMR Vaccination in Daratumumab-Treated Patients
Why Are Vaccinations Important in Hematologic Care?
Infection prevention is paramount in patients undergoing antibody-based treatment, such as with daratumumab (Darzalex; Johnson & Johnson). However, patients with multiple myeloma who have undergone autologous stem cell transplantation (ASCT) or are receiving antibody-based treatment are generally contraindicated for live-attenuated vaccines – including the measles-mumps-rubella (MMR) vaccine – due to the risk of disseminated infections.
Given the increasing use of anti-CD38 antibodies like daratumumab and the recent surge in measles cases – exceeding 1800 in the United States in 2025 – understanding the risks of live-attenuated vaccination in immunocompromised patients is critical. Addressing vaccine hesitancy and providing accurate information is also essential.
“Despite what the current health administration is putting out there, hopefully most of us can agree that vaccines have prevented and continue to prevent millions of deaths around the world,” stated James Davis, PharmD, BCOP, malignant hematology pharmacy specialist at the Medical University of South Carolina. Davis and his team conducted a multi-center retrospective study evaluating the safety of MMR vaccination in multiple myeloma patients receiving daratumumab after ASCT.
Assessing MMR Vaccination Safety
Data from 41 patients across five US academic medical centers was analyzed. MMR vaccinations were administered at the discretion of the treating oncologist. A key limitation of the study, acknowledged by Davis, was the lack of routine vaccine titer measurements. Investigators monitored for adverse events (AEs) following vaccination, including infectious complications, confirmed infections, rash, and malaise.
The initial MMR vaccination was administered at a median of 22 cycles (616 days) of daratumumab following ASCT, with four patients receiving a second dose. The median time from ASCT to MMR vaccination was 768 days. Common AEs included acute sinusitis (5%) and COVID-19 infection (5%), occurring a median of 8 days after vaccination. Importantly, no active MMR infections, hospitalizations, or deaths were reported post-vaccination.
Despite the limited sample size, Davis concluded that the findings suggest MMR vaccination is safe in immunocompromised patients with MM receiving daratumumab after ASCT. Pharmacists can play a crucial role in advocating for MMR vaccination, administering vaccines, and counseling patients and caregivers on the benefits and risks. Extensive monitoring is recommended for patients treated with daratumumab who receive a live-attenuated vaccine.