aExcludes laboratory derived hematologic adverse events (see Table 6).

bThe COSTART term for infection includes a subset of infections (e.g., upper respiratory infection). Other terms are mapped to preferred terms (e.g., pneumonia and sepsis). For a more inclusive summary see ADVERSE REACTIONS, Infectious Events.

Table 6: Hematologic Toxicity a (N = 230)  Endpoint
 Values
 
Platelets
 
Median nadir (cells/mm3)
 43,000
 
Per patient incidencea platelets<50,000/mm3
 53% (n = 123)
 
Medianb duration of platelets<50,000/mm3 (days)
 32
 
Grade 3/4 without recovery to Grade 2, N (%)
 16 (7%)
 
Per patient incidencec platelets<25,000/mm3
 21% (n = 47)
 
ANC
 
Median nadir (cells/mm3)
 690
 
Per patient incidencea ANC<1,000 cells/mm3
 63% (n = 145)
 
Medianb duration of ANC<1,000 cells/mm3 (days)
 31
 
Grade 3/4 without recovery to Grade 2, N (%)
 15 (7%)
 
Per patient incidencec ANC<500 cells/mm3
 25% (n = 57)
 
Hemoglobin
 
Median nadir (gm/dL)
 10
 
Per patient incidencea <8 gm/dL
 29% (n = 66)
 
Medianb duration of hemoglobin <8.0 gm/dL (days)
 23
 
Grade 3/4 without recovery to Grade 2, N (%)
 12 (5%)
 
Per patient incidencec hemoglobin <6.5 gm/dL
 5% (n = 11)
 

aGrade 3/4 toxicity was assumed if patient was missing 2 or more weeks of hematology data between Week 5 and Week 9.

bDuration of Grade 3/4 of 1,000+ days (censored) was assumed for those patients with undocumented Grade 3/4 and no hematologic data on or after Week 9.

cGrade 4 toxicity was assumed if patient had documented Grade 3 toxicity and was missing 2 or more weeks of hematology data between Week 5 and Week 9.

Delayed Adverse Reactions
Delayed adverse reactions, including hypothyroidism, HAMA, and myelodysplasia/leukemia, were assessed in 230 patients included in clinical studies and 765 patients included in expanded access programs. The entry characteristics of patients included from the expanded access programs were similar to the characteristics of patients enrolled in the clinical studies, except that the median number of prior chemotherapy regimens was fewer (2 vs. 3) and the proportion with low-grade histology was higher (77% vs. 70%) in patients from the expanded access programs.

Secondary Leukemia and Myelodysplastic Syndrome (MDS)
There were 44 cases of MDS/secondary leukemia reported among 995 (4.0%) patients included in clinical studies and expanded access programs, with a median follow-up of 29 months. The overall incidence of MDS/secondary leukemia among the 230 patients included in the clinical studies was 10% (24/230), with a median follow-up of 39 months and a median time to development of MDS of 34 months. The cumulative incidence of MDS/secondary leukemia in this patient population was 4.7% at 2 years and 15% at 5 years. The incidence of MDS/secondary leukemia among the 765 patients in the exp