Lower glomerular filtration rate predicts increased hepatic and mucosal toxicity in myeloma patients treated with high-dose melphalan

Masaharu Tamaki, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Yuko Ishihara, Koji Kawamura, Aki Tanihara, Miki Sato, Kiriko Terasako-Saito, Kazuaki Kameda, Hidenori Wada, Misato Kikuchi, Shun-ichi Kimura, Shinichi Kako, Yoshinobu Kanda

High-dose melphalan followed by autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for younger myeloma patients. However, the correlation between its toxicity and renal impairment is not clear. We analyzed this relationship, focusing on estimated glomerular filtration rate (eGFR) as an index of renal function. We evaluated 78 multiple myeloma patients who underwent ASCT following high-dose melphalan at our center. Patients were divided into a higher eGFR group (eGFR ≥ 60) and a lower eGFR group (eGFR < 60). Multivariate analyses revealed that lower eGFR was independently associated with alkaline phosphatase elevation (OR 10.2, P = 0.038), mucositis (OR 10.5, P = 0.032), grade 2-4 co-elevation of both aspartate aminotransferase and alanine aminotransferase (OR 21.3, P = 0.016), delay of reticulocyte engraftment (HR 0.524, P = 0.034), and delay of platelet engraftment (HR 0.535, P = 0.0016). However, lower eGFR was not correlated with overall survival or time-to-next treatment. In summary, renal dysfunction secondary to administration of high-dose melphalan was associated with increased hepatic and mucosal toxicity and delay of hematological recovery, but did not affect survival outcomes.