Final Results of a Large, Community Based Study Evaluating the Impact of First and Subsequent Cycle Pegfilgrastim on Neutropenic Events in NHL and HD Patients.
Authors: Noga Stephen J. , Choksi Janak , Ding Beiying , Dreiling Lyndah , Ozer Howard 
Published: April 2020

Abstract
Introduction: Most alterations to chemotherapy (CT) dose and schedule are due to neutropenic events, which mainly occur in the 1st cycle. A nationwide survey found that of 4522 patients (pts) with diffuse, aggressive non-Hodgkin’s lymphoma (NHL) treated with CHOP-like regimens in community practice, 40% experienced CT dose reductions, and 24% experienced CT dose delays (Lyman 2004). The ability of pegfilgrastim to reduce complications of CT-induced neutropenia has been established in clinical trials for pts receiving moderately (Vogel 2005) and highly (Holmes 2002) myelosuppressive CT. This prospective, community-based study evaluated the efficacy of 1st cycle pegfilgrastim in pts with NHL receiving CT in community practice.
Methods: Pts ≥ 18 yrs with cancers other than leukemia or MDS were eligible, including those with major comorbidities who are generally not eligible for clinical trials. Key exclusions were weekly CT and concurrent radiotherapy. Pts received pegfilgrastim 6mg ~24 hours after CT in each cycle (up to 8 cycles). Endpoints included neutropenic complications and CT dose reductions and delays. Additionally, average relative dose intensity (ARDI) was calculated for major standard regimens. Point estimates and 95% confidence limits (CL) are provided.
Results: This open-label, single-arm study enrolled 2249 pts at 319 sites. Of these, 325 pts with NHL and 46 pts with Hodgkin’s disease (HD) were included in the primary analysis set. The mean (SD) age was 65 (13) years for NHL pts and 41 (14) for HD pts. 69% of NHL pts and 26% HD pts had advanced (III–IV) disease, 90% of NHL pts and 98% of HD pts had ECOG status 0 or 1, and 31% of NHL pts and 26% of HD pts had major comorbidities (eg. vascular disease, diabetes). 49% of NHL pts received standard CHOP ± R (cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab) and 78% of HD pts received standard ABVD (bleomycin, dacarbazine, doxorubicin, vinblastine). Few pts experienced neutropenic complications (table). All serious adverse events were consistent with those observed in pts receiving myelosuppressive CT.
Conclusions: These results represent ‘real-world’ data as the only major entry criterion for pts was a confirmed diagnosis of malignancy. Pts in our study received myelosuppressive CT with very few neutropenia-related alterations in CT dose and schedule supporting the use of pegfilgrastim from the 1st cycle of CT. Use of pegfilgrastim allowed maintenance of RDI with minimal CT dose delays and reductions.
Incidence % (95% CL) NHL HD 1 physician reported; 2standard reference dose and planned cycle length were used to calculate DI in the denominator of RDI Hospitalization related to neutropenia in cycle 1 9 (6, 13) 4 (0.5, 15) Hospitalization related to FN in cycle 1 6 (4, 9) 0 (0, 8) FN in cycle 1 (ANC&lt;0.5×109/L and temperature 38.2°C) 8 (5, 12) 0 (0, 8) Incidence of grade 3/4 neutropenia in cycle 1 37 (32, 42) 4 (0.5, 15) Neutropenia-related IV antibiotic use in cycle 1 9 (6, 12) 4 (0.5, 15) Neutropenia-related CT dose reductions in cycle 21 2 (1, 5) 0 (0, 8) Neutropenia-related CT dose delays in cycle 21 2 (1, 5) 0 (0, 8) ARDI (mean % [SD])2 CHOP ± R every 21 days 77 (23) ABVD every 14 days 83 (26)