Darzalex Faspro Can Be Safely Administered in Patients with Elevated WBC and ANC
Yes, Darzalex Faspro (daratumumab) can be used to treat relapsed multiple myeloma in patients with leukocytosis (WBC 14.5 ×10⁹/L, ANC 12.6 ×10⁹/L), as elevated white blood cell counts are not a contraindication and may actually predict better treatment durability. 1
Rationale for Treatment
Higher white blood cell and monocyte counts correlate with improved treatment outcomes when daratumumab is combined with lenalidomide. A retrospective analysis of 324 relapsed/refractory multiple myeloma patients demonstrated that higher WBC counts (≥3500/μL) and higher monocyte counts (≥200/μL) predicted significantly longer time-to-next-treatment and better survival with the daratumumab-lenalidomide-dexamethasone (DLd) regimen. 1 Your patient's WBC of 14,480/μL and ANC of 12,580/μL exceed these favorable thresholds, suggesting they may derive substantial benefit from daratumumab-based therapy. 1
Evidence Supporting Daratumumab Use in Relapsed Multiple Myeloma
Daratumumab combinations are Category 1, preferred regimens for relapsed/refractory multiple myeloma according to NCCN guidelines. 2
Daratumumab-Bortezomib-Dexamethasone (DVd)
- The CASTOR trial demonstrated 82.9% overall response rate versus 63.2% with bortezomib-dexamethasone alone (P<0.001). 2, 3
- Median progression-free survival was not reached versus 7.2 months in the control arm (HR 0.39; P<0.001). 3
- After 40 months follow-up, median PFS was 16.7 versus 7.1 months (HR 0.31; P<0.0001). 2
- Patients with only one prior line of therapy showed the greatest benefit: median PFS 27.0 versus 7.9 months (HR 0.22; P<0.0001). 2
Daratumumab-Lenalidomide-Dexamethasone (DRd)
- The POLLUX trial showed 93% overall response rate versus 76% with lenalidomide-dexamethasone alone. 2
- Complete response rates were 43% versus 19% (P<0.001). 2
- Daratumumab reduced risk of progression by 66% and risk of death by 63% (P<0.0001). 2
- Benefits were independent of cytogenetic risk groups. 2
Safety Considerations with Elevated Blood Counts
The primary hematologic toxicities of daratumumab combinations include neutropenia and thrombocytopenia, not leukocytosis. 2
Expected Hematologic Adverse Events
| Toxicity | DVd Regimen | DRd Regimen |
|---|---|---|
| Thrombocytopenia (Grade 3-4) | 45.3% [2,3] | Increased risk [2] |
| Neutropenia (Grade 3-4) | 12.8% [3] | Increased risk [2] |
| Anemia (Grade 3-4) | 14.4% [3] | Common [2] |
Your patient's elevated WBC and ANC provide a hematologic reserve that may buffer against treatment-related cytopenias. 1
Infusion-Related Reactions
- Infusion reactions occur in 45-48% of patients, predominantly grade 1-2 and during the first infusion. 2, 3
- Grade 3 infusion reactions occur in only 8.6% of patients. 3
- 92% of infusion reactions occur with the first infusion only. 2
- Pre-medication with antihistamines, antipyretics, and corticosteroids mitigates these reactions. 4
Required Pre-Treatment Evaluation
Perform comprehensive red blood cell antigen typing before initiating daratumumab therapy. 2 Daratumumab binds to CD38 on erythrocytes and interferes with blood bank cross-matching techniques. 2
Use dithiothreitol-treated reagent erythrocytes for antibody screening, but transfuse only Kell-negative blood products. 2 Dithiothreitol eliminates daratumumab interference but removes the Kell antigen from test erythrocytes. 2
Monitoring Requirements
Implement the following monitoring schedule:
- Complete blood counts regularly to detect neutropenia, thrombocytopenia, and anemia. 4
- Thrombosis prophylaxis with aspirin or therapeutic anticoagulation for all patients receiving lenalidomide. 4
- Herpes zoster prophylaxis with acyclovir or valacyclovir when proteasome inhibitors are included. 4
Prognostic Scoring for Treatment Durability
A simple scoring model predicts durable response to daratumumab-lenalidomide-dexamethasone:
- 0 points: WBC ≥3500/μL AND β2-microglobulin <5.5 mg/L
- 1 point: Either WBC <3500/μL OR β2-microglobulin ≥5.5 mg/L
- 2 points: Both WBC <3500/μL AND β2-microglobulin ≥5.5 mg/L
Patients with score 0 showed significantly longer time-to-next-treatment and superior survival compared to scores 1 or 2 (P<0.001). 1 Your patient's elevated WBC of 14,480/μL places them in a favorable prognostic category if β2-microglobulin is also favorable. 1
Common Pitfalls to Avoid
Do not delay daratumumab therapy due to elevated WBC or ANC. These parameters are not contraindications and may predict better outcomes. 1
Do not interpret serum protein electrophoresis or immunofixation without considering daratumumab interference. Daratumumab is an IgG kappa antibody that can be mistaken for the patient's monoclonal protein if the myeloma also produces IgG kappa. 2 Mass spectrometry reliably distinguishes daratumumab from myeloma protein. 2
Do not perform blood bank typing after starting daratumumab. Complete red cell antigen screening must occur before the first dose. 2