A comprehensive real-world analysis of teclistamab treatment in relapsed/refractory multiple myeloma has revealed both encouraging efficacy data and important safety considerations that differ from clinical trial experiences. The multicenter study, involving 110 patients across five U.S. academic medical centers, provides critical insights into the practical application of this BCMA-targeted bispecific antibody since its FDA approval.
Efficacy Maintains Despite Challenging Patient Population
The real-world cohort demonstrated remarkable efficacy despite treating a significantly more challenging patient population than the pivotal MajesTEC-1 trial. With a median follow-up of 3.5 months, the overall response rate reached 62% among evaluable patients, with 51% achieving very good partial response or better and 20% achieving complete response.
Notably, this patient population was substantially more heavily pretreated, with 76% having penta-refractory disease compared to 35% in the MajesTEC-1 trial. The median number of prior therapies was 6, and 35% had received prior BCMA-targeted therapy, including 18 patients who had previously undergone BCMA CAR-T cell therapy.
"The ORR were not statistically different in patients with high-risk disease, extramedullary disease, and recipients of prior BCMA directed therapy," the researchers noted, suggesting teclistamab's broad applicability across different risk categories.
Safety Profile Reveals Higher Toxicity Rates
While efficacy remained robust, the safety profile in real-world practice showed concerning differences from clinical trial data. The incidence of grade 3 or higher cytokine release syndrome (CRS) was 3.6%, substantially higher than the 0.6% reported in MajesTEC-1. Similarly, severe immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 4.5% of patients compared to 0.6% in the pivotal trial.
The study documented one grade 5 ICANS event in a heavily pretreated patient who developed steroid-refractory ICANS and hemophagocytic lymphohistiocytosis syndrome after the first full dose. Overall, 56% of patients experienced CRS, with 93% being grade 1 or 2.
Infection Risk and Prophylaxis Strategies
Infectious complications emerged as a significant concern, with 40% of patients developing infections of any grade and 26% experiencing grade 3 or higher infections. The median time to first infectious event was 60 days, with bacterial infections being most common (48%), followed by viral (45%) and fungal infections (6.7%).
A critical finding was the protective effect of primary intravenous immunoglobulin (IVIG) prophylaxis. Patients receiving IVIG supplementation showed significantly lower infection rates, with a relative risk reduction of approximately 70%. The cumulative incidence of grade 3 or higher infections at 6 months was 17% in IVIG recipients compared to 43% in those without prophylaxis.
"Primary IVIG prophylaxis was employed in 46 patients and resulted in a statistically significant reduction in the cumulative incidence of ≥ grade 3 infection," the researchers reported.
Comparative Analysis Across BCMA Therapies
A separate analysis of FDA Adverse Event Reporting System data spanning 1,803 cases across three BCMA-targeted therapies provided additional context. This study examined idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), and teclistamab, revealing distinct toxicity profiles.
Teclistamab demonstrated the highest rates of life-threatening events (11.3%) and death (22.1%) among the three therapies. The analysis showed teclistamab had the highest odds ratio for non-relapse mortality (1.72), with infections being the predominant cause of fatal events.
In contrast, CAR-T therapies showed higher rates of CRS and neurotoxicity. Ide-cel exhibited the highest reporting odds ratio for CRS (1.8) and non-ICANS neurotoxicity (2.19), while cilta-cel was associated with specific neurological complications including Bell's palsy and Parkinsonism.
Clinical Implications and Future Directions
The real-world data suggests that while teclistamab maintains its therapeutic efficacy in routine practice, careful attention to toxicity management is essential. The higher rates of severe CRS and ICANS in real-world settings likely reflect treatment of patients with higher disease burden who may have been excluded from clinical trials.
The study's findings support the implementation of comprehensive infection prophylaxis strategies, particularly primary IVIG supplementation. All three cases of Pneumocystis jirovecii pneumonia occurred in patients without prophylaxis, reinforcing the need for routine preventive measures.
The research also highlighted the potential for teclistamab treatment following BCMA CAR-T therapy failure, with prior BCMA exposure not significantly impacting response rates. This finding is particularly relevant given the expanding landscape of BCMA-targeted therapies and the need for effective sequencing strategies.
Treatment Considerations
The data emphasize the importance of patient selection and monitoring strategies in real-world practice. While 94% of patients had progressive disease at treatment initiation, reflecting the urgent need for effective therapy, this high disease burden likely contributed to increased toxicity rates.
The study's diverse patient population, including 39% racial and ethnic minorities, provides valuable insights into teclistamab's performance across different demographic groups. The inclusion of patients with comorbidities typically excluded from clinical trials offers a more comprehensive understanding of the therapy's real-world applicability.
These findings collectively suggest that while teclistamab represents a valuable addition to the multiple myeloma treatment armamentarium, successful implementation requires careful attention to supportive care measures, particularly infection prophylaxis and toxicity monitoring strategies tailored to real-world patient populations.
