Tandon, Nidhi

AbstractAchievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10‐year period (2006‐2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi‐organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

Introduction The role of cardiac implantable electronic device (CIED) therapy in patients with ATTR-wt (senile) amyloid is not very well defined. It is unknown whether there is mortality benefit or harm with the implantation of CIEDs. Methods We performed a retrospective analysis of a prospectively collected registry of patients with biopsy proven ATTR-wt amyloid with cardiac involvement. These patients were followed up at Mayo Clinic, Rochester, Minnesota between Jan 1, 1985 to Sep 30, 2015. The follow-up of these patients was done via personal communication (written or verbal) and entered into the database. During analysis these patients were subdivided on the basis of the presence or absence of a CIED, cardiac involvement or not, and all-cause mortality analysed. The implantation of a CIED was analysed as a time-dependent covariate in the survival of these patients and Kaplan-Meier (K-M) survival plots created. Comparison between groups with CIED and those without CIED was made. In addition, CIEDs were subdivided into permanent pacemakers (PPM), defibrillators (ICDs) and cardiac resynchronization devices (CRT-P/D). Mortality among the patients with each device subtype was estimated and compared to overall mortality. Results 409 patients with ATTR-wt and cardiac involvement were reviewed with CIEDs implanted in 101 (25%) patients. The median follow-up (25th, 75th centile) was 2.4 (1.1, 4.3) years. Utilisation of ICDs in this population was higher than the general community in Olmsted county. There was no association in the overall survival or evidence of harm with CIED utilisation in patients with ATTR amyloidosis and cardiac involvement. Conclusions CIEDs utilisation remains high in ATTR-wt with cardiac involvement. Due diligence is needed in selecting the optimal patient for benefit prior to the implantation of CIEDs in this cohort. Further research is required to pool multi-centre amyloid registry data and determine if there is mortality benefit.

AbstractWe analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1‐93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22 m vs 32.3 m; P = .01) as compared to different therapy; but did not have any impact OS (30.8 m vs 51.1 m; P = .5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS.