Abstract

Abstract 1501

Background:

Clinical data guiding colony-stimulating factor (CSF) use with emerging regimens that incorporate targeted agents for treating hematologic malignancies are not readily available, even though many of these regimens can produce increased myelosuppressive side-effects. This review assessed the diligence of reporting around neutropenia, febrile neutropenia (FN), and neutropenic complications as well as the use of CSF and antibiotics in published clinical trials evaluating emerging regimens for the treatment of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, multiple myeloma (MM), or chronic lymphocytic leukemia (CLL).

Methods:

English-language reports of randomized controlled phase 3 studies of the selected hematologic malignancies published between January 2005 and June 2009 were identified by searching Medline, EMBASE, and Cochrane databases. Publications that met the inclusion criteria were retrieved and data on the incidence of neutropenia and its complications and CSF/antibiotic use were extracted. The percentage of publications that reported each outcome was then calculated.

Results:

Fifty seven trials that met the criteria were included in this analysis. Overall, 68% of trials reported on the incidence of grade 3/4 neutropenia (80%, MM; 71% CLL; 63% NHL, and 50%, Hodgkin lymphoma). However, fewer trials (18%) reported on the incidence of FN (57%, CLL; 20%, MM; 8%, NHL; and 0%, Hodgkin lymphoma). Similarly, only a few trials (4%) reported neutropenia-related hospitalizations (8%, NHL; 0% each for Hodgkin lymphoma, MM, and CLL). Primary prophylactic use of CSF was defined in the methods section of 19% of trials and CSF use was reported in the results section of 25% of trials. Use of antibiotics for FN treatment was defined in the methods section of 2% of trials and was reported in the results section of 9% of trials.

Conclusion:

In the published phase 3 studies evaluated in this analysis, clinically significant neutropenia and neutropenia-related events (including FN) were poorly or generally not described. Furthermore, the use of CSF and antibiotics was infrequently and inconsistently reported in the published literature of emerging regimens. A standardized approach to reporting neutropenic outcomes and the related use of supportive care measures can assist clinicians to prospectively manage the relevant toxicities associated with emerging regimens for hematologic malignancies. This is essential for the safe and effective transition of these regimens into broad clinical practice.

Table:

Reporting of myelotoxicity data in published phase 3 trials

Results section Reported data, n (%) 
NHL N = 24 Hodgkin lymphomaN = 6 MMN = 20 CLLN = 7 TotalN = 57 
Grade 3/4 neutropenia 15 (63) 3 (50) 16 (80) 5 (71) 39 (68) 
FN 2 (8) 0 (0) 4 (20) 4 (57) 10 (18) 
Infection/sepsis 22 (92) 4 (67) 13 (65) 6 (86) 45 (79) 
All cause hospitalization 5 (21) 0 (0) 1 (5) 1 (14) 7 (12) 
Neutropenia-related hospitalization 2 (8) 0 (0) 0 (0) 0 (0) 2 (4) 
Infection-related mortality 15 (63) 3 (50) 9 (45) 7 (100) 34 (60) 
Dose delays/interruptions 7 (29) 0 (0) 4 (20) 1 (14) 12 (21) 
Dose reductions 6 (25) 1 (17) 9 (45) 1 (14) 17 (30) 
CSF use 7 (29) 1 (17) 3 (15) 3 (43) 14 (25) 
Antibiotic use for FN treatment 3 (13) 0 (0) 2 (10) 0 (0) 5 (9) 
      
Methods section      
CSF use 12 (50) 4 (67) 7 (35) 5 (71) 28 (49) 
    Primary prophylaxis required 8 (33) 0 (0) 1 (5) 2 (29) 11 (19) 
    Secondary prophylaxis permitted 3 (13) 2 (33) 3 (15) 0 (0) 8 (14) 
    Following physician discretion/guidelines 2 (8) 2 (33) 3 (15) 3 (43) 10 (18) 
Antibiotic use for FN treatment 0 (0) 1 (17) 0 (0) 0 (0) 1 (2) 
Results section Reported data, n (%) 
NHL N = 24 Hodgkin lymphomaN = 6 MMN = 20 CLLN = 7 TotalN = 57 
Grade 3/4 neutropenia 15 (63) 3 (50) 16 (80) 5 (71) 39 (68) 
FN 2 (8) 0 (0) 4 (20) 4 (57) 10 (18) 
Infection/sepsis 22 (92) 4 (67) 13 (65) 6 (86) 45 (79) 
All cause hospitalization 5 (21) 0 (0) 1 (5) 1 (14) 7 (12) 
Neutropenia-related hospitalization 2 (8) 0 (0) 0 (0) 0 (0) 2 (4) 
Infection-related mortality 15 (63) 3 (50) 9 (45) 7 (100) 34 (60) 
Dose delays/interruptions 7 (29) 0 (0) 4 (20) 1 (14) 12 (21) 
Dose reductions 6 (25) 1 (17) 9 (45) 1 (14) 17 (30) 
CSF use 7 (29) 1 (17) 3 (15) 3 (43) 14 (25) 
Antibiotic use for FN treatment 3 (13) 0 (0) 2 (10) 0 (0) 5 (9) 
      
Methods section      
CSF use 12 (50) 4 (67) 7 (35) 5 (71) 28 (49) 
    Primary prophylaxis required 8 (33) 0 (0) 1 (5) 2 (29) 11 (19) 
    Secondary prophylaxis permitted 3 (13) 2 (33) 3 (15) 0 (0) 8 (14) 
    Following physician discretion/guidelines 2 (8) 2 (33) 3 (15) 3 (43) 10 (18) 
Antibiotic use for FN treatment 0 (0) 1 (17) 0 (0) 0 (0) 1 (2) 

CLL = chronic lymphocytic leukemia, CSF = colony-stimulating factor; FN = febrile neutropenia, MM = multiple myeloma, NHL = non-Hodgkin lymphoma.

Disclosures:

Gregory:Amgen Inc.: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; GlaxoSmithKline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx: Research Funding; Spectrum Pharmaceuticals: Consultancy. Abella:Amgen Inc.: Employment, Equity Ownership. Moore:Amgen Inc.: Consultancy, Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.