1. bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) proteins, was shown to achieve objective response rates amongst a majority of 33 patients with refractory or relapsed multiple myeloma participating in a phase 1 safety trial.
2. A majority of patients in this study were noted to have grade 3 hematologic adverse events. Non-hematologic adverse events were not as common and were often grade 2 or lower in severity.
Evidence Rating Level: 2 (Good)
Study Rundown: Multiple myeloma is an incurable plasma-cell cancer associated with the accumulation of immunoglobulin proteins. Previously proposed treatments for this disease have included monoclonal antibodies and immunomodulatory drugs, however these have not shown to be successful treatment methods and have eventually led to relapses amongst this patient group. Chimeric antigen receptor (CAR) T-cell therapy and anti-CD19 CAR T-cell therapy have proven to be promising agents for patients with leukemia and lymphoma. In this phase 1 study, researchers studied the safety of bb2121, an engineered compound which uses BCMA protein and autologous T-cell lentiviral vectors. The therapy was associated with high levels of hematologic-related adverse events including neutropenia, leukopenia, anemia, and thrombocytopenia, although most patients recovered neutrophil counts within 1 month. However, while other types of adverse events also occurred, the severity of non-hematologic adverse events were often grade 2 or below. Additionally, many patients showed an objective response to treatment, with almost half of patients experiencing a complete response.
While the sample size of this study was low and more safety and efficacy analyses are needed, these results show promise that bb2121 can be used to achieve the needed response efficacy rates for multiple myeloma treatment. Strengths of this study include its novel treatment approach and thorough evaluation of the treatment safety profile.
In-Depth [prospective cohort]: This phase 1, multi-center, open-label study enrolled 36 patients between 2016 to 2018. Eligible patients were adults with minimal physical disability, measurable multiple myeloma disease, and had undergone at least three previous therapies. All patients underwent lymphodepletion with fludarabine followed by a dose-escalation and a dose-expansion phase in which infusions of bb2121 was administered. The primary end point of this phase 1 study was safety. Any adverse events occurring through 8 weeks post-infusion, as well as through 6 months post-infusion were noted and grade according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Secondary end points included response rate and duration of response. Results for 33 patients were available for analysis for this study. Overall, 32 (97%) of patients had grade 3 or higher adverse events after treatment. The most common adverse events were hematologic in nature and included: neutropenia (28/33; 85%), leukopenia (20/33; 61%), anemia (19/33; 58) and thrombocytopenia (19/33; 58%). Of patients with grade 3 or higher cytopenia, 32 or 97% were noted to have recovered after 1 month to an absolute neutrophil count recovery of at least 1000 cells/mm3. The median recovery time to reach an absolute neutrophil count of at least 1000 cellsmm3 was 1.3 weeks (95% confidence interval [CI], 1.0-1.4). There were 25 patients (75%) who had noted cytokine release syndrome; 70% of patients had grade 1 or 2 symptoms while 6% had grade 3 symptoms. Neurologic adverse events were noted in 14 patients (42%) and were of grade 1 or 2 in severity in 13 patients (39%). The response rate to treatment was 85% (95% CI, 68.1-94.9%). A complete of stringent complete response was observed in 45% of patients. The median progression-free survival was 11.8 months (95% CI, 6.2-17.8).
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