Evaluating the adverse effects of melphalan formulations

Abstract

Introduction For multiple myeloma patients who respond to primary therapy, autologous hematopoietic stem cell transplant (HSCT) is considered standard of care with high-dose melphalan for transplant candidates. There are now two different melphalan formulations available, including a propylene glycol containing (PG-MEL) product and a propylene glycol-free (PG-free MEL) product. Although considered bioequivalent, there remains limited literature directly evaluating the adverse events between the two agents. We seek to assess the tolerability and severity of side effects between the two formulations in a real-life practice setting. Methods A retrospective, descriptive analysis was conducted of multiple myeloma patients who received autologous stem cell conditioning with either melphalan formulation when dosed at 100 mg/m2/dose for two consecutive doses. The primary outcome was the assessment of tolerability and severity of side effects. Tolerability was split into four major categories including hematologic toxicity, gastrointestinal toxicity, renal toxicity, and highest recorded mucositis grade. Results There were a total of 78 patients who received a melphalan preparation during the study. The median time to myeloablation and neutrophil engraftment was five and seven days post-HSCT, respectively, for all patients. Patients who received PG-free MEL were less likely to develop mucositis, with 22 (56%) reported highest grade 0, defined by World Health Organization oral toxicity scale, compared to those who received PG-MEL (33%), p = 0.04. Conclusion There were minimal differences in tolerability or side effects observed between PG-free MEL and PG-MEL. These data may assist in better understanding the anticipated adverse effects of a high-dose melphalan conditioning therapy.

Evaluating the incidence of engraftment syndrome with different melphalan formulations in adult multiple myeloma and immunoglobulin light chain amyloidosis patients undergoing autologous hematopoietic cell transplantation

“…[16][17][18] One study found PG melphalan to have a higher rate of mucositis and a separate study found PG-free melphalan to have a higher rate of diarrhea, though these findings have not been consistently reported in the literature. 16,17 Engraftment syndrome (ES) is a common complication of autologous HCT, typically developing within four days of granulocyte recovery. 19 ES may be classified by fever, skin rash, diarrhea, capillary leak syndrome, pulmonary infiltration, and hypoxia, among other symptoms.…”

“…14,15 While it was originally thought that PG-free melphalan may exhibit less adverse effects, comparative studies have found similar adverse effect profiles for both formulations. 16–18 One study found PG melphalan to have a higher rate of mucositis and a separate study found PG-free melphalan to have a higher rate of diarrhea, though these findings have not been consistently reported in the literature. 16,17…”

“…16–18 One study found PG melphalan to have a higher rate of mucositis and a separate study found PG-free melphalan to have a higher rate of diarrhea, though these findings have not been consistently reported in the literature. 16,17…”

β-Cyclodextrin-Based Nanosponges Inclusion Compounds Associated with Gold Nanorods for Potential NIR-II Drug Delivery

“…Among the different molecules that have been studied in the context of their potential anti-tumor effects, polyphenols and nitrogen mustards have shown to be effective against various types of tumor cell lines, such as lung, multiple myeloma, ovarian, breast and gastric cancer, among others [ 18 , 19 , 20 , 21 ]. Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally occurring polyphenol phytoconstituent obtained from Curcuma longa .…”