Toxicity of weight-based vs. flat dosing for immune checkpoint inhibitors in patients with low weight: Retrospective analysis from a tertiary care center.

Abstract

e14616 Background: Immune checkpoint inhibitors (ICI) have come to the forefront of cancer therapy. Barring Ipilimumab, all other ICIs are dosed at flat doses for ease of administration. Pharmacokinetic studies have shown a wide range of peak and trough concentrations for flat doses. However, for underweight patients (<50 Kg), when one looks at weight-based dosing, it may seem that flat dose may deliver excessive amounts of the drug within a short period of time, which in turn may cause an immune-related adverse event (irAE). We conducted a retrospective study comparing the toxicities and outcomes of weight based and flat doses in underweight patients treated with ICI. Methods: This is a retrospective study of patients receiving ICI for any cancer-related indication. Patients receiving chemotherapy with pembrolizumab, nivolumab and/or ipilimumab were included. Patients on other ICI were excluded. All grade toxicities were recorded, and Odds ratio (OR) was calculated using the Z-test. Results: 313 patients were included where 255 (81.5%) were females, median age 66 years (range 19-93), and 225 (72%) were White. Lung cancer was the most common histology (n-170, 54%) followed by H&N (n-34, 11%) and GI cancers (n- 27, 9%). The median weight was 47 Kgs (range: 31-50). 252 patients (80.5%) received flat dose ICI and 61 patients (19.5%) received weight-based ICI, most of whom (n-45, 74%) received prior to 2018. Median ICI cycles was 4 (2-9) vs. 5 (3-10). Single agent PDL-1 inhibitor was prescribed to 205 patients (65%) of which 120 received pembrolizumab (59%) and 85 received nivolumab (41%), and 89 patients (28%) received ICI in combination with chemo or targeted therapy. 94 patients (30%) experienced all grade toxicities. Thyroid dysfunction (n-47, 15%) and colitis (n-24, 8%) were the most common. There was a non-significant trend towards lower toxicity in weight-based dosing: 13 (21.3%) vs. 81 (32.1%), OR =0.57, 95% CI (0.29 - 1.11) p =0.10, and a trend toward less hospitalization or need for treatment for iRAE: 8 (13.1%) vs. 55 (21.8%), OR =0.54, 95% CI (0.24 - 1.20) p=0.13. Significantly higher toxicity was recorded when chemotherapy-ICI or TT-ICI combinations: 56 (24.8%) vs. 38 (43.7%) OR = 0.42, 95% CI (0.25 - 0.71) p= 0.001. There was no difference in death or needing hospice care rates: 43 (70.5%) vs 169 (67.1%), OR= 1.17 (95% CI, 0.64 - 2.16) p= 0.61. Conclusions: Compared to standard flat dosing, weight-based dosing of ICI was associated with a trend towards lower iRAE in patients < 50 Kgs without a difference in survival. These results urge the oncology community to consider the potential financial toxicity savings if weight-based dosing of ICI is adopted more broadly in underweight patients without negatively impacting outcomes, large scale and prospective studies are needed to support this hypothesis.