Feasibility and Toxicity of Pharmacokinetic (PK)-Directed Dosing of Evomela® (propylene glycol free melphalan, PGF-MEL) for Multiple Myeloma (MM) and AL Amyloidosis (AL) Patients Undergoing Autologous Hematopoietic Stem Cell Transplant (AHCT)

Abstract

point in the gut microbiome and was not detected at baseline and at T+30. At the genus level, in oral wash samples, Haemophilus parainfluenzae abundance significantly decreased between T-2 and T+7 (P = .01) and subsequently increased at T+30 (P = .005). In the gut microbiome, Desulfovibrio D168 species significantly decreased from baseline to T+7 (P = .03). Conclusion and Future Directions: Microbial composition and bacterial diversity is altered significantly during HCT, with the lowest diversity noted during marrow aplasia. This change is likely multifactorial owing to the conditioning regimen, antimicrobial exposure and immune dysregulation. We hypothesize that this state of microbiota dysbiosis could contribute to the development of unwanted toxicities during HCT including: infections, oral mucositis and gastrointestinal toxicities (nausea, vomiting and diarrhea) due to bacterial domination by a pathogen. The next objective(s) is to correlate these microbiome changes to clinical endpoints including engraftment rates and toxicities. Further analysis is also underway to explore the fungal component of the microbiome in the same cohort.

Comparable outcomes using propylene glycol-free melphalan for autologous stem cell transplantation in multiple myeloma

“…38 Further, several recent studies have demonstrated the feasibility of using pharmacokinetic-directed dosing of PG-free MEL to optimize serum melphalan concentrations. 24, 39 Future prospective studies should clarify these findings and investigate if this method could be used to improve ASCT outcomes while sparing patients of undue toxicities.…”

Pharmacokinetics of High-Dose Propylene Glycol–Free Melphalan in Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation

“…For example, a split-dosing schema starts at an initial dose of 100 mg/m 2 with PK monitoring and increasing the second dose proportionately based on first-dose PK to achieve the desired level of exposure. Shah et al [21] reported early results with a 10-mg/m 2 test dose and subsequent PK-based dosing. Although the collection of PK and calculation of a target dose was feasible using results from the test dose, the target AUC could not be achieved in this study.…”

Busulfan, melphalan, and bortezomib compared to melphalan as a high dose regimen for autologous hematopoietic stem cell transplantation in multiple myeloma: long term follow up of a novel high dose regimen

“…There appears to be increasing enthusiasm for intensifying the preparatory regimen in MM using other approaches, including 2 randomized phase II studies comparing bendamustine and melphalan [22] as well as BEAM (carmustine, etoposide, cytarabine, Melphalan) (NCT03570983) to Mel200 in addition to the above mentioned PETHEMA-GEM study comparing BuMel to Mel200 [16] . Similar to our work with busulfan, pharmacokinetic based melphalan dosing which was once thought not feasible is being explored utilizing propylene glycol free melphalan (Evomela) [23], [24] . Finally, the incorporation of proteasome inhibitors into the preparatory regimen is particularly attractive as they have been shown to enhance the sensitivity of multiple myeloma tumor cells to chemotherapeutic agents without affecting normal hematopoietic cells [25] .…”