Immune checkpoint inhibitors (ICI) are used increasingly and earlier to treat multiple cancers. Although rates of on-treatment myelotoxicity are low, there are no published data on the long-term effects of ICI. This is a pilot study to evaluate the impact of prior ICI exposure on chemotherapy-related myelotoxicity in patients in the Phase I setting.
We conducted a retrospective chart review of patients treated between 2012 and 2016 in the Drug Development Unit, The Royal Marsden Hospital. Multivariate logistic regression (including number of previous treatment lines and type of chemotherapy) was used to assess possible relationships between G3/4 neutropenia or thrombocytopenia and previous treatment with immunotherapy in patients receiving combination chemotherapy and targeted agents.
We identified 99 patients (median age 62 years [range 34-79]; chemotherapy partners: cisplatin, carboplatin and paclitaxel). Fourteen patients (14%) received prior immunotherapy (PI) and 85 (86%) had no prior immunotherapy (NPI). Patient characteristics, including baseline full blood count, previous pelvic radiotherapy, sites of metastasis and serum albumin, were comparable between the 2 groups, apart from number of previous treatment lines, which was lower in the PI patients (median 1.5 vs 2, p = 0.003). The odds of G4 neutropenia were higher in the PI group (OR = 7.1, 95% CI = 1.7-29.6, p = 0.007). PI was associated with significantly increased odds of G3/4 thrombocytopenia (OR = 14.4, 95% CI = 2.7-77.4, p = 0.002) on chemotherapy. In multivariate analysis, incorporating lines of prior chemotherapy (OR 1.3, 95% CI = 1.0-1.5, p = 0.037) and type of chemotherapy (carboplatin vs others: OR 2.3, 95% CI = 0.9-6.2, p = 0.094), the odds of developing G3/4 myelotoxicity were significantly higher in PI patients (OR 4.3, 95% CI: 1.3-14.4, p = 0.02).
In our small cohort, previous treatment with immunotherapy was associated with the development of G3/4 myelotoxicity, especially thrombocytopenia, on subsequent chemotherapy. These preliminary data require further prospective validation but may impact on decision making regarding optimal sequencing of systemic therapy.
Clinical trial identification
Legal entity responsible for the study
The Royal Marsden Hospital NHS Foundation Trust
J. de Bono: Consulting or advisory role: Astex, AstraZeneca, Genentech, Genmab, GSK, Merck, Pfizer, Sanofix Research Funding: AstraZeneca, Genentech, GSK, Sanofi, Janssen. U. Banerji: Receipt of grants/research supports: AstraZeneca, Chugai, Onyx, BTG Receipt of honoraria or consultation fees: Astex, Karus Therapeutics, Novartis, Vernalis. All other authors have declared no conflicts of interest.