Botanical Product Use Among Multiple Myeloma Patients in Commercial Drug Trials

Abstract

Botanical medication use is frequently reported among patients with cancer, including those undergoing treatment. The use of botanical medicines among patients with solid tumors has been frequently studied and concerns raised about the potential for botanical-drug interactions. To date, limited information exists about botanical medicine use for multiple myeloma patients. Furthermore, relatively few studies of botanical medicine use among cancer patients enrolled in commercial clinical trials have been undertaken, despite the importance of these trials for establishing the safety and efficacy of new drugs. We sought to describe botanical concomitant medication use among patients with multiple myeloma enrolled on commercial trials of anti-myeloma investigational products, the content of trial protocols regarding concomitant botanical medications, and the potential for botanical-drug interactions. Using internal FDA databases, we identified eight randomized, multi-arm trials of products submitted to FDA for regular approval from 2015 to 2018 with concomitant medication datasets that used the standard World Health Organization Anatomical Therapeutic Chemical (WHO ATC) classification. Botanical products were identified by reviewing concomitant medications from the ATC classes of unassigned/blank, all other therapeutic products, all other non-therapeutic products, and unspecified botanical and traditional medications. Frequently prescribed botanical laxatives such as senna were excluded. We pooled data across the eight trials and compared botanical use by region, disease characteristics, and sociodemographic characteristics. We also assessed the types of botanical products used. Products were categorized into types using the plant name identified from the dictionary or preferred name, where available. We also evaluated whether trial protocols provided guidelines regarding botanical medication use. Finally, we assessed if any of the products could affect CYP3A4 by reviewing information from the Memorial Sloan Kettering Cancer Center's online database for integrative medicine and the Natural Medicines online database for integrative therapies. We evaluated data from 4,712 patients recruited from 40 countries in the pooled intention-to-treat (ITT) populations, of whom 303 (6.4%) used botanical products at any time (on/off trial) and 257 (5.5%) used botanical products while on trial. Nearly all patients (91%) who used botanical products used just a single type of botanical product. The maximum number of products used per patient was three. Patients who used botanical products and those who did not were similar in terms of age, sex, and prior lines of therapy. However, use varied by region. In Asia, 27% of patients used botanicals, compared to 10% in North America and Oceania and 3% in Western Europe. Many botanical medications (49% of all products) could not be classified by plant name. Frequently used medications included ginkgo biloba (6% of all products), milk thistle (5% of all products), and saw palmetto (4% of all products). All trial protocols provided guidelines regarding the use of concomitant medications. Specifically, the protocols included the need to record any concomitant medications and discussed which medications and/or medication classes were required, allowed, and prohibited/restricted. In all protocols we examined, botanical products were not explicitly mentioned in the discussion of concomitant medications. Of the 55 botanical products that could be classified by plant names, preliminary review identified 15 products (27%) that had possible interactions with CYP3A4, although for many of these the evidence was based on in vitro or animal studies. One product, camellia sinensis, was noted to inhibit bortezomib, which was an active agent used in several of the included trials. In conclusion, multiple myeloma patients enrolled in commercial drug trials rarely use botanical medications, although use is more common in some regions. Although use is infrequent, sponsors may wish to consider inclusion of guidance regarding botanical medications in their protocol section relating to concomitant medications, particularly because of the potential for botanical-drug interaction. Of concern is the inability to group many products by plant name, which may obscure the identification of any potential interactions with drugs. Disclosures No relevant conflicts of interest to declare.