Can Daratumumab Cause Diarrhea?
Yes, daratumumab can cause diarrhea, and this is a well-documented adverse effect across multiple clinical trials and treatment combinations.
Incidence of Diarrhea with Daratumumab
Diarrhea is consistently reported as one of the most common adverse reactions with daratumumab-based regimens, though the frequency varies depending on the combination therapy used:
Combination-Specific Rates
With Lenalidomide and Dexamethasone: Diarrhea occurred in patients receiving this combination, and it is listed among the most frequently reported adverse reactions (≥20%) 1
With Bortezomib and Dexamethasone: Diarrhea occurred in 32% of patients in the daratumumab arm versus 22% in the control arm (without daratumumab), representing a 10% absolute increase. Grade 3 or higher diarrhea occurred in 3% of patients 1
With Carfilzomib and Dexamethasone (twice-weekly): Diarrhea was reported in 32% of patients receiving daratumumab-based therapy versus 14% in the control arm. Grade 3-4 diarrhea occurred in 3.9% versus 0.7% 1
With Carfilzomib, Lenalidomide, and Dexamethasone (quadruplet therapy): Diarrhea was the most common adverse event, occurring in 68% of patients, with 18% experiencing grade 3-4 severity 2
Meta-Analysis Evidence
Multiple systematic reviews and meta-analyses confirm the association between daratumumab and diarrhea:
A 2023 meta-analysis of randomized controlled trials demonstrated that daratumumab-based regimens significantly increased the risk of diarrhea compared to control regimens 3
A 2025 systematic review of meta-analyses confirmed diarrhea as a consistent adverse drug event associated with daratumumab across multiple studies 4
Clinical Implications
Severity and Management
- Most cases of diarrhea are grade 1-2 (mild to moderate)
- Grade 3-4 (severe) diarrhea is less common but can occur, particularly with quadruplet regimens
- In rare cases (2% in the CANDOR trial), diarrhea led to serious adverse reactions requiring hospitalization 1
Important Caveats
- The incidence of diarrhea appears higher with combination regimens than with daratumumab monotherapy
- Quadruplet regimens (four-drug combinations) show the highest rates of diarrhea
- The contribution of daratumumab versus the backbone therapies (lenalidomide, bortezomib, carfilzomib) to diarrhea is difficult to isolate, as these agents themselves can cause gastrointestinal side effects
Patient Counseling
According to FDA labeling, patients should be educated about probable side effects of daratumumab, including gastrointestinal symptoms 1. Healthcare providers should proactively discuss diarrhea management strategies when initiating daratumumab-based therapy.
Bottom line: Diarrhea is a common and expected adverse effect of daratumumab-based regimens, occurring in approximately one-third of patients depending on the combination used, with most cases being manageable and of mild-to-moderate severity.