Supervisors info:
Καστρίτης Ευστάθιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Γαβριατοπούλου Μαρία, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Σταματελόπουλος Κίμων, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Translated title:
An early, within the first month, and deep response, should be the goal of therapy in AL amyloidosis
Summary:
Immunoglobulin light chain amyloidosis (AL) is caused by misfolded free light chains (FLCs) which are produced by a small and usually indolent plasma cell clone. The amyloid fibrils deposit in various tissues and cause severe dysfunction of multiple organs such as kidney, heart, liver or peripheral nervous system (Dittrich et al., 2017). Furthermore, recent studies indicate that FLCs could be responsible for direct toxicity(Kastritis et al., 2019, Milani et al., 2017a). Despite the progress in treatment approaches (autologous transplantation, bortezomib, lenalidomide) that has offered a significant survival benefit to intermediate and low risk patients, 20-30% of subjects will die within 3-6 months from therapy beginning, mostly due to heart failure (Milani et al., 2018a, Kastritis et al., 2015). Thus it is important to evaluate frequently the therapy response, at least every 2 cycles or 3 months, in order to change strategy and give to high risk patients the opportunity of a rescue therapy(Merlini et al., 2013, Kastritis et al., 2016). The assessment of therapy effectiveness is based on validated criteria which evaluate the cardiac, renal and hematologic response (Palladini et al., 2012a). The measurement of serum free light chains (sFLCs) is essential in the evaluation of hematologic response response. In the present study we tried to confirm the significance of an earlier assessment of response for patients with AL, especially for high risk subjects with heart involvement. In particular, FLCs blood levels have been measured at the time of diagnosis and at the end of first and third month from the initiation of frontline therapy. The major outcome is that the achievement of early and deep response, within the first month of therapy, should be the goal of therapy in patients with AL amyloidosis, especially those with stage 3 disease. Less than a VGPR after 3 months of therapy should prompt to change therapy. The most active combination should be used to rapidly reduce toxic FLCs, however, even among those who achieve an early VGPR, early mortality remains high, indicating the advanced cardiac dysfunction and late recognition of the disease.
Keywords:
AL amyloidosis, Free light chains, Early response, First month, Overall survival
