Angiotensin-I Converting Enzyme Inhibitors and the Survival of Patients with Multiple Myeloma Treated by Autologous Stem Cell Transplantation.

Introduction:

The aim of our study was to analyze the impact of angiotensin-I converting enzyme inhibitors (ACEI) on the outcome of patients with multiple myeloma (MM) treated by autologous peripheral blood stem cell transplantation (APBSCT), as it has been reported that low angiotensin-converting enzyme (ACE) activities are associated with poor prognosis in multiple myeloma (MM).

Patients and Methods:

Patients with MM who underwent APBSCT (n=168) were studied retrospectively. Patients taking ACEI alone or in combination with other antihypertensive agents during the APBSCT were allocated to the ACEI group (n=25; 15%). The ACEI group was compared both to all other patients (n=143; 85%) and to patients with hypertension who were taking other or no antihypertensive medication (n=44). The induction chemotherapy consisted of 4 cycles of VAD. For stimulation, cyclophosphamide was given, followed by G-CSF. High-dose melphalan was used as conditioning.

Results:

The ACEI and non-ACEI groups were similar in terms of age, initial levels of albumin, beta2-microglobulin, CRP, LDH, performance status, stage according to IPI and Durie-Salmon criteria, myeloma type, and maintenance treatment. Patients with hypertension (n=69) and patients without hypertension (n=99) had similar overall survival (OS) after APBSCT (65.5 months versus 60.9, respectively; p=0.561), and progression-free survival (PFS) after APBSCT (32.6 months versus 29.6 months; p=0.635). Patients taking ACEI had significantly worse OS after APBSCT (32.7 months) compared to patients not taking ACEI (65.2 months; p=0.033). Among patients with hypertension, OS was significantly shorter in the ACEI group than in the non-ACEI patients (p=0.024). Statistically significant differences were also observed in PFS between hypertensive patients treated by ACEI and other hypertensive patients (19.3 months versus 48.6 months, respectively; p=0.041). Most deaths in both groups were myeloma-related. Renal failure was a main or contributing cause of death in 3 patients from the ACEI group and in 8 patients from the non-ACEI group (p=0.233). Also, there was a trend favoring non-ACEI hypertensive patients in comparison to ACEI hypertensive patients in the number of complete responses after PBSCT (40% versus 17%; p=0.058).

Conclusion:

In this retrospective study we have found that patients with MM and hypertension treated with ACEI at APBSCT have worse survival in comparison to patients with MM receiving other or no antihypertensive drugs. Further research in this area could lead to important insights into the pathophysiology of MM and to the reevaluation of ACE activity as a prognostic factor in MM.