Background:
Carfilzomib is a novel and irreversible inhibitor of the proteasome and is currently used in relapsed or refractory multiple myeloma patients. Although studies reported recently the increased incidence of adverse cardiac events during Carfilzomib therapy such as heart failure or arrhythmias, so far there are only limited data to identify patients at risk.

Purpose:
This prospective study aims to assess the use of CMR in detecting early (subclinical) cardiotoxic changes and also to determine parameters which could predict the onset of late changes in cardiac function after 3 months follow up of multiple myeloma patients receiving carfilzomib.

Patients & Methods:
Patients diagnosed with multiple myeloma and scheduled to undergo treatment with carfilzomib perform three CMR examinations: before (baseline) and two times after start of chemotherapy (3-5 days and 3 months).
The collected CMR data include standard morphological and functional parameters for left and right ventricle (LV/RV) i.e. ejection fraction (EF), enddiastolic volume/body surface area (EDV/BSA), endsystolic volume/BSA (ESV/BSA), ED LV myocardial mass, mitral and tricuspid annular plane systolic excursion (MAPSE, TAPSE) as well as tissue characterization (LV global T1 and T2 Mapping) and deformation parameters (LV and RV global longitudinal and circumferential myocardial strain (GLS) (GCS)). These data were compared between baseline, 1^st and 2^nd follow up studies.

Results:
Until now 10 patients have been included and investigated at 1.5T MRI scanner. Two Patients dropped out from the 2^nd follow up due to change of chemotherapy regimen or death.
This interim analysis showed that mean functional and tissue characterization parameters were within normal range at baseline and during follow-up except the MAPSE which was reduced in the 2^nd follow up (baseline 11.7±1 mm, 1^st 11.8±1.2 mm and 2^nd 10.7±2 mm).
Mean global LV Strain parameters were within normal range at baseline and stable in the follow-up examinations. However, regarding segmental LV strain analysis, three patients showed an increase in the number of abnormal LV segments in the 2^nd follow up compared to the baseline study which was associated with the appearance of clinical symptoms in two of them such as dyspnea or reduced exercise ability during the follow up studies.
Mean RV GCS was reduced in the follow-up studies (baseline -18±1.8%, 1^st -16.7±2.5% & 2^nd -14.8±2.7%) indicating a potential effect on cardiac deformation. However, with the limited number of patients, so far none of the parameters reached significance (P = 0,065).

Conclusion:
These preliminary results show the feasibility of using CMR in the follow up of patients treated with Carfilzomib. However, a larger cohort is needed to further evaluate the myocardial deformation changes. Detection of changes in myocardial deformation may allow early diagnosis and also prevention of the Carfilzomib-related cardiotoxicity.

Figure 4: Comparison between Myocardial strain analysis at baseline & 2^nd follow up. Exemplary visualization of circumferential strain as ‘bullseye’ image (upper panel) and 2/3/4 chamber view (lower panel) of a patient at baseline and 12 weeks after initiation of Carfilzomib therapy showing the increase in number of abnormal LV segments (segments with reduced myocardial strain). The color bar indicates strain values. 2Ch, 2 chamber view; 3Ch, 3 chamber view; 4Ch, 4 chamber view; LV, left ventricle; RV, right ventricle.