Citations

e19532 Background: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat and/or bone marrow biopsy, but at times organ biopsy is required. Methods: We studied 612 patients with systemic light chain amyloidosis to characterize the tissues used to establish the diagnosis Results: The median number of tissue samples biopsied for CR staining was 3. Ninety-five percent of bone marrow (BM) biopsies were stained for CR, while 79% of patients had fat aspiration performed for CR staining. Overall, 76% of patients underwent both procedures. CR stain sensitivity was 69% in BM samples, 75% in fat aspiration and in 89% for both sources combined. CR stain sensitivity was 97-100% for heart, renal and liver biopsies. 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive safer biopsy would have established the diagnosis. Predictors of need for organ biopsy were male sex, limited organ involvement and lack of fat aspiration (Table). Conclusions: Fat aspiration is underutilized for histologic confirmation of amyloidosis. Organ biopsies (particularly renal biopsies) were performed at a high rate, which represents a failure to recognize the disease (i.e. failure to screen with a light chain assay etc.). Early awareness of amyloidosis in the differential diagnosis of patients with organ dysfunction may lead to fewer unnecessary organ biopsies [Table: see text]

e19530 Background: Neuropathy is a universal symptom of patients with POEMS syndrome, which makes the use of bortezomib less appealing. However, proteasome inhibitors (PIs) can provide rapid and deep hematologic responses in plasma cell disorders. Because there is very little data regarding the use PIs in POEMS syndrome, we performed a study of patients with POEMS syndrome treated with PIs. Methods: Among the 167 patients with POEMS syndrome seen at our institution between 2001-2016, we identified 12 patients who received a PI. One patient receiving < 1 cycle of bortezomib because of worsening neuropathy was included but was excluded from response analyses. One patient received 2 different PIs at separate points during the disease course and each course was considered separately. Four response categories were considered: hematologic, PET, VEGF and clinical as previously described (Dispenzieri et. al AJH 2015). Results: Among the 12 patients who received 13 courses of therapy, the median age at PI initiation was 59; 8 patients were male. Median number of prior therapies was 1 (0-4) and median time from diagnosis to initiation of PI was 75 months. Excluding steroids, regimens were as follows: bortezomib, n=3; bortezomib and cyclophosphamide, n=4; carfilzomib, n=1; and ixazomib, n=1. With a median follow-up from PI initiation of 18 months, the median duration of treatment was 7 months (1-18). Three patients achieved a hematologic CR. Of 6 patients with an abnormal baseline VEGF, 3 achieved normalization VEGF levels. Of 5 patients with an abnormal baseline PET, 2 achieved normalization of their PET. Two patients had improvement of their neuropathy, with the rest having stable symptoms. Of 9 patients with fluid overload, 8 improved. Only 2 patients stopped therapy due to worsening neuropathy related to PIs. Median PFS and OS from initiation of PI were 50 months and 53 months, respectively. Conclusions: We show that PI use in patients with POEMS syndrome can be safe and effective. Nearly 75% of patients treated with bortezomib had no exacerbation of their neuropathy. Clinical improvement in severe fluid overload symptoms (edema, ascites, pleural effusions) is almost universal, making PI-based therapy an attractive potential option in these patients.

8049 Background: Complete response in AL is defined as normal FLC ratio with negative serum and urine immunofixation. It is not clear if high involved serum FLC (hIFLC) in a patient with normal ratio may contribute to ongoing amyloid formation and hence affect outcomes. Methods: Data of 1308 patients (pts) with systemic AL seen within 90 days of diagnosis, at Mayo Clinic between 2006-2015, was analyzed retrospectively. Among these, 369 pts had 2 consecutive normal FLC ratio values after 1st line treatment and form the study population. Log rank test was used to estimate survival differences. Results: Among these 369 pts, pts with hIFLC at 1streading of normal FLC ratio (hIFLC1; n=170; 46.1%) were compared to those who did not (n=199; 53.9%). At diagnosis, the median age [61.5 vs 60.8 years (y); p=0.2], proportion of males (62.4 vs 58.3%; p=0.4), percentage of pts with renal involvement (73.5 vs 64.8%; p=0.07), in mayo stage I / II / III / IV (32.9% / 23%/ 27.3% / 16.8% vs 43.6 %/ 22.9% / 18.1% / 15.4%; p=0.1), with bone marrow plasma cells >10% (24.2 vs 30%; p=0.2) and with presence of t(11; 14)(48.4 vs 60; p=0.08) was similar, while cardiac (67.5 vs 53.3%; p=0.006) and hepatic (18.2 vs 9.1%; p=0.01) involvement was higher in hIFLC1 group. The median follow-up from diagnosis was 6.1 y (95% CI; 5.6, 6.8). The median progression free survival (PFS) in pts who had hIFLC1 was lower than for those who did not; 2.6 y (95% CI; 1.9, 4.5) vs 5.2 y (95% CI; 4.6, 6.4), p<0.0001, as was the median overall survival [OS; 6.7 y (95% CI; 4.5, 8.3) vs not reached (NR), p<0.0001]. We performed a more stringent comparison for pts with 2 consecutive hIFLC values (hIFLC2; n=112; 30.4%) versus not (n=257; 69.6%). The median PFS (3.2 y; 95%CI; 2.2, 4.5 vs 5.6 y; 95% CI; 4.7, 7.1; p<0.0001) and OS (7.8 y; 95% CI; 6.4, NR vs NR; 95%CI; 9.5, NR; p<0.0001) were significantly reduced in pts with hIFLC2 versus not as well. A multivariate analysis confirmed an impact of hIFLC1 and hIFLC2 on PFS/OS independent of serum creatinine. Conclusions: In pts with systemic AL, persistent elevation of the involved FLC predicts for poor prognosis (independent of serum creatinine) even among those who achieved normal FLC ratio after 1st line treatment.

8048 Background: Organ response (OR) in AL is often delayed and difficult to predict early. Methods: We retrospectively analyzed 1308 patients (pts) with newly diagnosed AL from 2006 – 2015 to determine factors which could predict for OR. Results: Median age was 64 years (yr) and Mayo Stage was: 1 (22%); 2 (23%); 3 (25%); 4 (31%). Organ involvement was: cardiac (74%, n=932); renal (59%, n=738), liver (16%, n=205); gut (24%, n=310) and autonomic (12%, n=152). 59% (n=765) had > 1 organ involved, including 43% (n=567) with > 1 critical organ (heart, kidney, liver) involved. Treatment was: ASCT based (28%, n=330, N=1186), bortezomib based (24%, n=281), alkylator based (33%, n=392), others (5%, n=54) and none (10%). In evaluable pts, VGPR or better rates were: 53% at 6 months (m) (N=625), 72% at 12 m (N=465) and 57% overall (N=688). Table 1 lists OR at various time points. Complete OR in all involved critical organs was seen in: 51% (n=308, N=600), partial response (at least 1 OR when >1 organ involved) in 12% (n=73) and none in 37% (n=219). Complete OR was associated with better overall survival (OS) than partial or no OR (median OS: not reached vs 42 m vs 29 m; P <0.0001). In multivariate model the following variables at baseline or 1 yr mark were predictive of complete OR: lower Mayo Stage (p=0.01), fewer critical organs involved (p=0.007), higher baseline GFR (p=0.03), female sex (Complete OR 60% vs 47%; p=0.04) and VGPR at 1 yr (Complete OR 70% vs. 36%; p <0.0001). Other factors included in the model were age (p=0.9), bilirubin (p=0.1) and transplant (p=0.2). All aforementioned factors were significant in univariate analysis. Conclusions: Achievement of response in all involved critical organs is associated with better survival in AL pts than partial or no OR. Various baseline factors and VGPR at 1 yr can predict for achieving complete OR, with 70% pts who achieve VGPR at 1 yr having a complete OR. [Table: see text]

8047 Background: Presence of CPCs by six color MFC is associated with worse outcomes in multiple myeloma (MM). Using a slide based immunofluorescence assay, CPCs are associated with worse prognosis in AL, but outcomes with MFC are not known. Methods: We retrospectively analyzed 154 patients (pts) from Jan 2008 – Dec 2015 with AL who had CPCs analyzed by MFC at diagnosis. Results: CPCs were present in 42% pts (n = 64, median = 88 per 150,000 events, range 6-17844). Table 1 lists baseline characteristics, treatment and response. In univariate analysis, bone marrow (BM) plasma cells > 15% (p<0.0001), dFLC > 60 mg/dL (p=0.02) and presence of active MM (p=0.0004) were associated with detectable CPCs. In multivariate (MV) model, only BM plasma cells > 15% predicted for presence of CPCs (p=0.02). There was no difference in hematologic or organ response in the 2 groups. Median follow up was 43 months (m). Pts with detectable CPCs had worse survival than those without detectable CPCs (90 m vs. 98 m, p=0.0004). In MV analysis model with Mayo Stage and detectable CPCs, presence of CPCs at diagnosis was independently associated with poor survival (CPCs p= 0.02, Mayo Stage p < 0.0001). Conclusions: Presence of detectable CPCs is an independent adverse prognostic factor for survival in AL. Comparatively fewer pts with detectable CPCs underwent early ASCT, which may reflect a more aggressive disease presentation. [Table: see text]