Kourelis, Taxiarchis

e19534 Background: Our group has developed a mass spectrometry (MS) method that can identify circulating monoclonal proteins, based on their unique molecular mass signatures. Given the propensity for patients with AL amyloidosis to have MS patterns consistent with post-translational modifications (PTMs), we posed the question whether these changes might be present long before the diagnosis of AL and potentially serve as a predictor for AL in patients with an asymptomatic plasma cell dyscrasia (aPCD). Methods: We included 64 patients with AL who had a preceding aPCD and who had stored serum samples at both time-points. The mass/charge (m/z) of monoclonal LC peaks (P) was noted for each sample. Presence of a PTM was defined as the presence of ≥1 “heavy” Ps at a particular charge state. A P was considered heavy if its m/z exceeded the right sided 95% C.I. of the m/z distribution of the respective normal LC. We used 9 patients with relapsed multiple myeloma (MM) without AL as controls. Results: Prior aPCDs were MGUS (N = 33), smoldering myeloma (n = 9) and MM (N = 1). In 21 patients aPCD was not further classified with a bone marrow biopsy. The median interval between aPCD and AL diagnosis was 77 months. At aPCD diagnosis, 42 patients had a single, typical P and 21 patients (33%) had PTMS: 13 patients had a single heavy P; 5 patients had 2 P (only one of which was heavy); and 3 patients had 2 heavy peaks. No PTMs were noted in our MM controls. The m/z of all typical and heavy P observed at aPCD remained unchanged for 63 patients as they transitioned to AL, which suggests no new PTMs occurred with the exception of one patient, who had a single PTM at aPCD diagnosis, but developed 2 additional heavy P appearing at +1232 and +1392 Dalton at AL diagnosis, suggestive of new PTMs. In all but 3 aPCD, the typical P was more abundant relative to heavy P. Heavy P abundance increased in 6 patients as they transitioned from the aPCD to the AL state and exceeded that of the typical P in 3 patients, suggestive of increasing abundance of existing PTMs in these cases. Conclusions: Pre-existing PTMs are present in 1/3 of AL patients and not in MM and can be used to identify patients at risk for AL. New PTMs are uncommon, but the relative abundance can change over time.

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.

8038 Background: Daratumumab-based Combination Therapies (DCT) with bortezomib (V)/ lenalidomide (R)/ pomalidomide (P) and dexamethasone (d) showed exceptional activity in RRMM in trials. Experience outside of trials since the approval of Daratumumab (D) in 2015 is limited. Methods: RRMM pts seen at Mayo Clinic, MN from 12/2015 -12/2016 were reviewed. Pts who received ≥ 1cycle of DCT were included. Time-to-event analyses were done from date of starting DCT. Common terminology criteria for adverse events v4.0 were used to grade toxicities. Results: Of 130 pts, 59% were males and median age at DCT initiation was 67 (43-93) years, ECOG performance score was ≥2 in 29%. Pts were classified as mSMART high (22%), intermediate (22%) or standard (56%) risk. Median time from diagnosis to initiation of DCT was 51.3 (5-156) months (m), and median number of prior therapies was 4 (1-14). 14% of pts were refractory to prior D monotherapy. Fifty-three (41%), 34 (26%) and 25 (19%) received DPd, DRd and DVd respectively. Eighteen (14%) pts received ‘other’ DCT. Median time to first response (≥ PR) was 3.1 m (95% CI 2.1-4.6). Overall response rate was 46%, [CR-2%, VGPR-18%, PR-26%]. Minimal response was seen in 17%, with clinical benefit rate of 62%. Median estimated follow up from initiation of DCT was 5.5 m (CI 4.2-6.1). The median duration of response was 6.1 m [CI 5.1- not reached (NR)]. Median progression free survival (PFS) was 5.5 m (CI 4.1-7.8) and median time to next therapy (TTNT) was 5.9 m (CI 4.6-9.4). Median PFS for DPd, DRd, DVd and other DCTs were 4.6 (CI 2.7-NR), 7.8 (CI 5-NR), 3.9 (CI 2.1-NR) and 3.9 (CI 2.8-8.2) m, respectively (p = 0.3). Median PFS for quadruple refractory (n = 28) MM was 2.8 m (CI 2.2-5.3) vs 5.9 m (CI 4.9-NR) for the rest (p < 0.01). Median overall survival (OS) from DCT was NR (CI 11.4-NR). Grade 3 or higher hematological toxicities were seen in 42% of pts. Other toxicities included infections (37%), fatigue (31%), infusion reactions (16%) and diarrhea (10%). Conclusions: DCT are effective in RRMM, but the PFS remains short particularly in quadruple refractory pts, reflecting the challenges encountered in managing heavily-pretreated, and often less fit patients, in routine practice.

8032 Background: Human adipocytes can contribute directly to the in vitro growth and progression of multiple myeloma (MM) cell lines. Clinically, an elevated body mass index (BMI) has been associated with an increased risk of MGUS and a shorter time to progression (TTP) of MGUS to MM. However, the impact of BMI on the risk of early progression to MM from a more advanced plasma cell disorder such as smoldering MM (SMM) remains unknown. Methods: This study included patients (pts) with a known or new diagnosis of SMM evaluated at the Mayo Clinic, Rochester from January 2000-December 2010. Pts were classified based on their BMI as: normal (< 25) and elevated (>/= 25) BMI. Progression to symptomatic MM was defined by the development of hypercalcemia, renal insufficiency, anemia or lytic bone lesions. Results: There were 306 pts with a diagnosis of SMM who were included in this analysis. The median follow up was 106 months. There were 203 (66%) pts who progressed to symptomatic MM at last follow up. The median BMI of the group was 27.5 (Range: 17.2 – 56.4). There were 228 (75%) pts with an elevated BMI. There were 76 (28%) pts who had myeloma defining events (MDEs) such as a serum free light chain ratio > 100 or > 60% clonal bone marrow plasma cells at initial evaluation. MDEs were present in 17% and 33% of pts with a normal and elevated BMI respectively (P = 0.011). The median TTP of SMM to MM in pts with a normal and elevated BMI was 64 and 36 months respectively (P = 0.0006). The 2-year progression rate of SMM to symptomatic MM in pts with a normal and elevated BMI was 16% and 42% respectively (P < 0.0001). Upon limiting the analysis to only SMM pts without MDEs at initial evaluation (N =187), the 2-year progression rate to symptomatic MM with a normal and elevated BMI was 15% and 33% respectively (P = 0.013). In a multivariable model, only elevated BMI (P = 0.004) and increasing clonal bone marrow plasma cells (P = 0.001) was statistically significant in predicting for a 2-year progression to MM. Conclusions: SMM pts with an elevated BMI appear to have a higher risk of early progression to MM than those with a normal BMI. This study provides evidence of a potentially modifiable risk factor for the progression of SMM to MM and warrants confirmation in larger studies.

8014 Background: t(11;14) is a standard risk cytogenetic marker in MM. Methods: We reviewed 366 patients with MM who had t(11;14) by FISH and 732 age and period-matched controls without t(11;14), seen at our institution from 2004 to 2014 and outcomes were analyzed using time to first progression or death (PFS1) and overall survival (OS). Results: For the t(11;14) group at diagnosis, the median age was 63.7 yr (range, 22.1-95.4) with 64.5% of patients being male. Eighty nine (24.3%) patients were above 70 yr of age at diagnosis. 33.8%, 40.3% and 25.9% patients belonged to ISS 1, II and III stages respectively. 13% patients had elevated LDH. Monosomy 17 or del 17p were identified in 10.6% patients. The median follow up period was 56.9 months (m) (95% CI: 54.6-62.2) and 209 (57.1%) patients were alive at last follow-up. Among patients receiving proteasome inhibitor (PI)-based, immunomodulator (IMiD)-based, PI+IMiD based or other agent based induction therapy, 71.2%, 70.3%, 90.4% and 37.5% patients respectively attained ≥PR as best response to induction (p < 0.01). During their course, 223 (60.9%) patients underwent stem cell transplant. Median PFS1 and OS were 23.1 (CI: 20.8-27.9) and 78.6 (CI: 66.7-105.9) m respectively. Among the controls, high risk cytogenetics (HRC) was present in 142 (19.4%), and the median OS was 83.8 m (CI: 70.8-97.0) being comparable to t(11;14) group (p = 0.8). For all 1098 patients, using a Cox-proportional hazards model with age > 70 years, induction therapy (novel agent-based vs others), cytogenetics [HRC vs t(11;14) without HRC vs no HRC or t(11;14)], and ISS stage III vs II/I as predictors, age > 70 years [HR-2.2 (CI: 1.8-2.8) and p < 0.01], ISS III vs ISS II/I [HR-1.4 (CI: 1.1-1.8) and p < 0.01] and HRC [HR of 2.1 (CI: 1.6-2.8) vs no HRC or t(11;14) (p < 0.01) and 1.9 (CI = 1.4-2.6) for t(11;14) without HRC (p < 0.01)were associated with reduced OS. The risk for reduced OS did not differ between t(11;14) without HRC, and those without t(11;14) or HRC [HR-1.1 (CI: 0.9-1.4), p = 0.4]. Conclusions: Our study characterizes the outcomes of a large cohort of MM patients with t(11;14) at diagnosis. Advanced age, HRC and advanced stage at diagnosis were associated with worse OS in our cohort. t(11;14) MM without HRC does not differ in outcome compared to non-t(11;14) MM without HRC.

6572 Background: Cancer patients (pts) receive complex care that may cause physical, emotional, & financial sequelae. Current practice limits clinician time to address patient concerns. The Patient Reported Outcome Quality Of Life (PROQOL) system was developed as a self-reported electronic questionnaire to assess symptoms, QOL and provide data about bothersome issues. Our aim was to determine if the PROQOL system improves QOL without negatively impacting routine clinic workflow. Methods: Eligible pts had multiple myeloma, amyloidosis, head & neck or gynecologic cancer seen in Hematology/Oncology clinics at Mayo Clinic, and were stratified by stem cell transplant and active treatment status. Pts were randomized 2:1 to PROQOL system or usual care. PROQOL system was offered prior to every visit. Pts select from various categories about their single biggest concern, and receive a printed list of actionable resources based on selected concern. Clinicians also receive the PROQOL results to review with pts. Providers and pts randomized to PROQOL completed a “was it worth it survey” (WIWI). An 8 item Linear Analogue Self-Assessment was used to assess QOL. The study was powered to detect a 0.5 standard deviation difference in QOL between groups. Herein we report the planned results of first 6 months. Results: Among the first 118 pts accrued, 55% were female, median age was 63 (32-86), & 93% were on therapy. Median time from diagnosis to PROQOL was 26 months. The PROQOL system took 3.6 minutes to complete. Baseline median QOL (range) was 7 (3-10) for both groups. The most common PROQOL issue selected was “cancer & diagnosis” (36.5%) followed by “physical health” (35.3%). Specific concerns were related to treatment plan, prognosis, fatigue, sleep, and neuropathy. WIWI showed: 71% of pts thought it was worthwhile, 83% would participate again, 80% would recommend it, & 65% used resources provided. 80% of providers reported the PROQOL did not interfere with care & 75% believed the pt wellbeing may improve. Conclusions: Notably treatment plan & prognosis remain pts' greatest concern despite being over 2 year from diagnosis.The PROQOL system demonstrates integrated PRO reporting in clinic is quick & worthwhile to pts & providers.