Welcome to the final day of coverage from the latest advances on myeloma treatment presented at the American Society of Clinical Oncology (ASCO) meeting. Highlights from today featured updates on tocilizumab pretreatment to improve tolerability of the BCMA bispecific antibody Tecvayli (teclistamab), as well as investigational CAR T-cell therapy and maintenance therapy. Here’s a quick recap!
Tocilizumab has proven to be an effective treatment to lessen the impact of cytokine release syndrome (CRS), which presents as flu-like symptoms experienced by most patients who receive either CAR T-cell therapy or bispecific antibody treatment. Early phase trials suggest that tocilizumab could prevent the development of CRS without limiting the anti-myeloma activity of bispecific antibody therapy.
In the first abstract, (Abstract: 7517) researchers from the Netherlands reported their findings from an 8-month follow up of patients from a MajesTEC-1 cohort, investigating the use of tocilizumab pretreatment for the reduction of CRS in patients treated with Tecvayli. The data showed that a single dose of tocilizumab pretreatment reduced the risk of CRS in 24 patients with RRMM by 65%. In this study, tocilizumab was given by injection up to 4 hours before the first dose of Tecvayli was given.
Outpatient administration of Tecvayli is being examined in the early phase OPTec study. Early data (Abstract: 7528) from 10 patients showed that tocilizumab pretreatment 2 to 4 hours before the first dose of Tecvayli reduces the incidence of CRS and neurotoxicity.
These findings suggest that tocilizumab treatment before the first dose in a community clinic setting could reduce the need for patients to visit the hospital for drug administration and make Tecvayli more accessible for those who have limited treatment options. Further data from ongoing clinical trials with more patients will shed light on the potential role tocilizumab pretreatment could play in reducing the risk of CRS and improving treatment accessibility.
GPRC5D, a receptor expressed on multiple myeloma cells, has become a promising target for novel immunotherapeutic strategies such as bispecific antibodies and CAR T-cell therapy, especially for patients who no longer respond to BCMA-targeted therapies such as Tecvayli and Elrexfio (bispecific antibodies) as well as Abecma and Carvykti (CAR T-cell therapy options).
In this abstract (Abstract: 7511) , investigators from China presented their findings from an early phase trial evaluating OriCAR-017, a CAR T-cell therapy designed to specifically target GPRC5D, in patients with RRMM. After 2 years of follow up, all 10 patients who received a single infusion of OriCAR-017 responded to therapy, with 80% achieving a stringent complete response, and a 100% minimal residual disease negative rate—that is, no disease was detected after treatment—was confirmed 3 months after therapy. Low-grade cytokine release syndrome was the most common side effect reported.
Future studies will provide more information on the clinical potential of GPRC5D-targeted CAR T-cell therapy in RRMM.
Maintenance therapy with Empliciti (elotuzumab) and Revlimid (lenalidomide) may improve progression-free survival in patients with myeloma who recently underwent a stem cell transplant, according to recent results from an early phase trial. In addition, this combination maintenance therapy was safe and tolerable in patients, according to Dr. Sheeba Thomas and colleagues from the University of Texas MD Anderson Cancer Center.
Data from their abstract (Abstract: 7509) revealed that progression free survival (PFS)—that is, the length of time during and after treatment in which a patient is living with a disease that does not get worse—was 75 months. Most common side effects were low white blood cell counts, respiratory infections, diarrhea, and fatigue. Additional studies will help determine the role and potential benefit of this combination maintenance therapy.
Venetoclax is a potent and selective oral BCL-2 inhibitor with demonstrated anti-myeloma activity in patients with RRMM and a translocation of chromosomes 11 and 14 [t(11;14)]. The phase 3 CANOVA study evaluated the safety and efficacy of venetoclax plus dexamethasone (VenDex) for patients with t(11;14)-positive RRMM who have had at least two prior lines of therapy. The results showed numerically longer PFS compared with Pomalyst (pomalidomide) and dexamethasone (PomDex), though the difference was not statistically significant. The most common adverse events experienced by patients treated with VenDex included infection and diarrhea.
In the final abstract (Abstract 7510), researchers from Canada presented findings of their analysis of patient biomarkers—that is, substances like proteins, genes, and DNA that show the presence and severity of myeloma—to identify patients who may respond to treatment with VenDex. Patients with either normal 1q or (1q) gain—that is, the presence of one extra copy of DNA—had numerically improved PFS, ORR, and MRD negativity with VenDex compared to PomDex.
The findings suggest that treatment with VenDex can help patients with (1q) gain. Additional studies will help determine the potential role of VenDex and RRMM treatment.
Keep an eye out for MMRF updates from the annual European Hematology Association meeting later this month!
