Pegfilgrastim Use and Risk of Bleomycin Induced Pulmonary Toxicity in Hodgkin Lymphoma

Background

Hodgkin lymphoma (HL) is a potentially curable malignancy when treated with bleomycin-containing chemotherapy regimens such as ABVD at full dose intensity. Growth factor support may be necessary to maintain dose intensity. The major limitation of bleomycin use is the development of bleomycin induced pulmonary toxicity (BPT). Bleomycin-induced cell injury stimulates an inflammatory response n the lung. G-csf has been shown in animal models to augment this response. Clinically, filgrastim (g-csf) use appears to increase the risk of BPT in HL, with BPT occurring in 25.6% of ABVD treated pts who were exposed to filgrastim in one study¹. It remains unclear whether pegylated filgrastim, with a delayed onset of action, also leads to increased BPT. We previously reported² a small series of HL pts who were predominantly treated with pegfilgrastim with ABVD and did not find increased BPT. We now report an update of our experience, including a larger subset who did not receive pegfilgrastim.

Methods

All cases of HL diagnosed from 1/2004 to 2/2016 and treated at MetroHealth Medical Center, a safety net hospital in Cleveland, OH, were reviewed. Pts who did not receive bleomycin or received filgrastim were excluded. 69 cases were identified, all of whom were treated with ABVD. 34 of these patients (Group A) received pegfilgrastim (all at least 24 hours after bleomycin) while 35 (Group B) did not receive pegfilgrastim. BPT was defined by the presence of new pulmonary symptoms, radiographic findings of interstitial infiltrates and absence of infection.

Results

Group A: mean age of 38 (19-73), stage I-2/34, II-17/34, III-6/34 and IV-9/34. 30 of 34 patients received full doses of ABVD, 2 of 34 patients received 4 cycles of ABVD followed by radiation therapy, one patient received ABD and one patient received ABVD with bleomycin on hold after 3 cycles due to lung toxicity. Complete remission (CR) was found in 27 of 34 patients, partial remission (PR) was identified in 5 of 34 patients and response was unavailable in the remaining 2 patients. 3/34 pts developed relapse of HL. Of 34 patients, one (2.9%) developed BPT (age 44).

Group B: mean age of 37 (22-69), stage II-18/35, III-11/35 and IV-6/35, 26 of 35 patients received full doses of ABVD and 4 of those were given radiation therapy. 2 patients had bleomycin held due to pulmonary toxicity. CR was identified in 29 of 35 patients, PR was found in 3 patients and response was unavailable in the remaining 3 patients due to being lost to follow up or transfer of care. 3/35 pts developed relapse of HL. Of 35 patients, 3 developed BPT (8.6%). All 3 patients were older than age 40 (42-69).

Conclusions

In this retrospective study, pegfilgrastim use with ABVD in HL was associated with a low (2.9%) risk of BPT. This risk was not higher than in our HL ABVD treated pts who did not receive pegfilgrastim (8.6% risk of BPT). All of the pts who developed BPT were >age 40. The 2.9% risk of BPT with pegfilgrastim use contrasts with much higher previously reported BPT with filgrastim use (25.6%)¹. One explanation for this may be the delayed onset of pegfilgrastim.

¹Martin WG et al. J Clin Oncol. 2005; 23 (30): 7614

² Janakiram M and O'Brien TE. ASH Proceedings. 2008; 112: Abstract #4950