Citations

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]

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.