In the Phase 3 SUCCESSOR‑02 trial, which Grade 3 or higher adverse event was most frequently reported in patients treated with mezigdomide combined with carfilzomib and dexamethasone?

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Last updated: October 9, 2026 • View editorial policy

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Neutropenia (Answer C)

In the Phase 3 SUCCESSOR-02 trial, neutropenia was the most commonly reported Grade 3+ adverse event in patients receiving mezigdomide plus carfilzomib and dexamethasone (Kd), occurring in 61% of patients. 1

Evidence from SUCCESSOR-02

The trial enrolled 606 patients with relapsed/refractory multiple myeloma who had received at least one previous regimen including anti-CD38 antibodies and lenalidomide. The safety profile clearly demonstrated:

  • Neutropenia (Grade 3-4): 61% in the mezigdomide-Kd arm versus only 9% in the Kd-alone arm
  • Infections (Grade 3-4): 34% versus 16%
  • Overall Grade 3-4 adverse events: 84% versus 56%

The dramatic difference in neutropenia rates (61% vs 9%) represents a 7-fold increase attributable to mezigdomide addition, making it by far the most frequent severe hematologic toxicity 1.

Comparison with Other Answer Options

While the trial reported multiple Grade 3+ adverse events:

  • Thrombocytopenia was not specifically highlighted as a predominant toxicity in the mezigdomide arm
  • Hypogammaglobulinemia was not reported among the most common Grade 3+ events
  • Diarrhea occurred but was not among the most frequent severe toxicities

Clinical Management Implications

The high rate of Grade 3-4 neutropenia (61%) requires:

  • Proactive monitoring: Complete blood counts should be checked regularly, particularly during the first several cycles
  • Growth factor support: Consider prophylactic G-CSF in high-risk patients or those who develop Grade 3-4 neutropenia
  • Infection prophylaxis: Given that 34% experienced Grade 3-4 infections, antimicrobial prophylaxis should be strongly considered
  • Dose modifications: The study protocol included dose adjustments for hematologic toxicity, which were generally effective in managing these events

The infections were noted to be "mostly manageable with standard clinical practice and supportive care," but the substantial rate necessitates vigilant monitoring 1.

References

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