Abstract: Introduction: Panobinostat (PAN), a potent pan-deacetylase inhibitor, was the first agent of its class to produce a statistically significant and clinically meaningful increase in the median progression-free survival (PFS) of patients (pts) with relapsed or relapsed and refractory multiple myeloma (MM) in a phase 3 trial. In the PANORAMA 1 trial, the addition of PAN to treatment with bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) led to a significant increase in high-quality responses (near-complete response/complete response [nCR/CR]; 27.6%) vs treatment with placebo (Pbo), BTZ, and Dex (15.7%; P = .00006). Pts in the PAN-BTZ-Dex arm also had a significantly prolonged median PFS of 12.0 months vs 8.1 months in pts treated with Pbo-BTZ-Dex (hazard ratio [HR] , 0.63; P 〈 .0001). Further, subgroup analysis showed that the PFS benefit was maintained in pts with previous exposure to BTZ and immunomodulatory drugs (IMiDs; 10.6 vs 5.8 months; HR, 0.52). These results supported the recent US FDA approval of PAN in combination with BTZ and Dex for the treatment of pts with relapsed or relapsed and refractory MM who have received ≥ 2 prior regimens including BTZ and an IMiD. Here, we present a detailed analysis of the effect of response on clinical outcomes in a subpopulation of PANORAMA 1 pts with prior exposure to BTZ and IMiDs. Methods: Response outcomes were analyzed for the subgroup of PANORAMA 1 pts with prior exposure to BTZ and IMiDs based on modified European Society for Blood and Marrow Transplantation criteria, including nCR/CR and partial response (PR). A landmark analysis at 12, 18, and 24 weeks was performed using a Cox regression model to assess the median PFS in pts who achieved nCR/CR and PR. Results: Among pts with prior exposure to BTZ and IMiDs, the nCR/CR rate was higher in the PAN-BTZ-Dex arm (22.3% [95% CI, 14.4-32.1]) vs the Pbo-BTZ-Dex arm (9.9% [95% CI, 4.2-16.6] ). In the PAN-BTZ-Dex arm, the landmark analysis at 12 weeks demonstrated a median PFS of 13.7 months in pts achieving nCR/CR vs 8.1 months in pts achieving PR (HR, 0.34 [95% CI, 0.12-0.96]). Similarly, pts achieving nCR/CR in the Pbo-BTZ-Dex arm had a median PFS of 12.2 vs 7.8 months for pts achieving a PR (HR, 0.74 [95% CI, 0.27-2.01] ). Landmark analysis at 18 weeks demonstrated a median PFS of 15.8 months for pts with nCR/CR vs 10.3 months for pts with a PR in the PAN arm (HR, 0.30 [95% CI, 0.12-0.75]) and 14.1 vs 9.0 months (HR, 0.76 [95% CI, 0.29-1.98] ) in the Pbo arm for pts with nCR/CR and PR, respectively. The 24 week landmark assessment revealed a median PFS in the PAN arm of 15.8 months for pts with nCR/CR vs 13.7 months for pts with PR (HR, 0.32 [95% CI, 0.14-0.74]) and, in the Pbo arm, a median PFS of 12.2 months for pts with nCR/CR vs 11.2 months in pts with PR (HR, 0.93 [95% CI, 0.36-2.43] ). Conclusions: Treatment with PAN-BTZ-Dex is associated with a 〉 2-fold increase in the rate of nCR/CR in pts with relapsed or relapsed and refractory MM compared with control arm. Among study pts who had received prior treatment with BTZ + IMiDs, those who achieved nCR/CR after treatment with PAN-BTZ-Dex demonstrated a prolonged PFS compared to pts who achieved PR.These data highlight the importance of achieving deep responses with PAN-BTZ-Dex in this subpopulation, suggesting that the achievement of such responses may be linked to improved clinical outcomes. Disclosures San Miguel: Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees. Beksac:Janssen-Cilag: Consultancy, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Dimopoulos:Onyx: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Genesis: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Jedrzejczak:Pfizer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Onconova: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Siritanaratkul:Pfizer: Research Funding; Roche: Research Funding; Novartis: Research Funding; Janssen-Cilag: Research Funding. Schlossman:Millennium: Consultancy. Hou:Novartis: Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lonial:Bristol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Einsele:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau. Sopala:Novartis Pharma: Employment, Equity Ownership. Bengoudifa:Novartis: Employment. Corrado:Novartis: Employment, Equity Ownership. Binlich:Novartis: Employment. Richardson:Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

Abstract: Introduction: In the randomized placebo controlled phase 3 trial PANORAMA 1 the pan-deacetylase inhibitor (pan-DACi) panobinostat combined with bortezomib and dexamethasone (PAN-BTZ-Dex) led to a statistically significant and clinically relevant increase in progression free survival in patients (pts) with relapsed or relapsed and refractory multiple myeloma (Pbo-BTZ-Dex; 12.0 vs 8.1 months; hazard ratio 0.63, P 〈 0.0001). Gastrointestinal (GI) toxicity, particularly diarrhea, a known class-effect of pan-DACi and BTZ, was the most common non-hematologic adverse event (AE) observed in both treatment arms, occurring at a higher incidence in the PAN-BTZ-Dex arm. Optimal management of GI toxicity, especially diarrhea-related AEs, in pts who receive PAN-BTZ-Dex could help maximize treatment outcomes. Here we present a detailed analysis of pts with diarrhea on the PANORAMA 1 study to inform strategies to reduce the effects of diarrhea and improve efficacy. Methods: The PANORAMA 1 trial included 12 cycles of treatment with two treatment phases (TP1: eight 3-week cycles; TP2: four 6-week cycles). In TP1, pts were randomized to receive oral PAN (20 mg) or Pbo administered thrice weekly for the first 2 weeks, with intravenous BTZ (1.3 mg/m2) administered on days 1, 4, 8, and 11 and Dex (20 mg) administered orally on the days of and after BTZ. In TP2 (for pts demonstrating clinical benefit), PAN or Pbo were administered similarly but BTZ was administered once-weekly (days 1, 8, 22 and 29) with Dex on the day of and after BTZ. For each cycle, prevalence and incidence for diarrhea AEs were determined; these were characterized by grade, improvement in grade, worsening of grade, and resolution of diarrhea. Results: In the PANORAMA 1 trial, a total of 260/381 (68.2%) pts treated with PAN-BTZ-Dex and 157/377 (41.6%) pts treated with Pbo-BTZ-Dex reported AEs of diarrhea; most were grade 1 or 2 (PAN-BTZ-Dex: 42.8% vs Pbo-BTZ-Dex: 33.7%). Grade 4 diarrhea was rare (PAN-BTZ-Dex: 1.3%; Pbo-BTZ-Dex: 0.5%). Dose adjustments/interruptions for diarrhea occurred in 26% on the PAN-BTZ-Dex arm and 9% on the Pbo-BTZ-Dex arm. Treatment discontinuation due to diarrhea occurred in 4.5% on the PAN-BTZ-Dex arm and 1.6% on the Pbo-BTZ-Dex arm. Serious AEs of diarrhea occurred in 11.3% on PAN-BTZ-Dex arm and 2.4% on Pbo-BTZ-Dex arm. There was no hemorrhagic diarrhea on the PAN-BTZ-Dex arm and in 1 pt in the Pbo-BTZ-Dex arm. In the majority of pts (56.2%) in the PAN-BTZ-Dex arm, diarrhea occurred for the first time in cycles 1-4 and was primarily grade 1/2; first onset occurred rarely in TP2 (Figure). Cumulative incidence of diarrhea on the PAN-BTZ-Dex arm plateaued by cycle 6 (61.9% by cycle 6; 68.2% overall). The cumulative number of pts with complete resolution of diarrhea (defined as resolved diarrhea that did not recur on treatment) increased over the course of the study. During treatment, 67.7% (258/381) in PAN-BTZ-Dex arm had either no diarrhea or complete resolution of their diarrhea. Analysis of diarrhea management by grade and treatment phase revealed that most pts received medication to manage the diarrhea. Antidiarrheal medications were administered to 70.8% (184/260) pts with diarrhea across all grades; loperamide was used most commonly. However, many pts with grade 1/2 diarrhea had no action taken in TP1: grade 1 - 58% (115/198); grade 2 - 26% (33/127), suggesting suboptimal management of diarrhea. Conclusions: These data demonstrate that diarrhea in pts who received PAN-BTZ-Dex occurs primarily in the first 1-4 cycles of treatment with cumulative incidence reaching a plateau around cycle 6. Majority of pts with diarrhea had complete resolution during treatment. Although diarrhea was commonly observed in pts who received PAN-BTZ-Dex in the PANORAMA 1 trial, it was manageable and seldom led to treatment discontinuation; however, some pts with grade 1/2 diarrhea did not receive proactive management. Optimal management of diarrhea with prompt intervention including antidiarrheal medication and dose holds/adjustments of BTZ and PAN at the first sign of loose stools may help to maintain pts on therapy and thus improve outcomes with PAN-BTZ-Dex. Future trials should seek to employ these strategies for pts who experience GI toxicity, and should consider subcutaneous administration of BTZ. In addition, studies using combinatorial agents with less overlapping GI toxicity with PAN may further improve safety in this setting. Figure 1 Figure 1. Disclosures Richardson: Takeda: Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Celgene: Consultancy, Honoraria. Jedrzejczak:Amgen, Novartis: Consultancy, Research Funding. Guenther:Novartis: Consultancy, Research Funding. Siritanaratkul:Novartis: Research Funding; Roche: Research Funding; Janssen: Research Funding. Schlossman:Millennium: Consultancy. Hou:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Onyx: Consultancy; Sanofi: Consultancy. Sopala:Novartis Pharma AG: Employment. Panneerselvam:Novartis: Employment, Equity Ownership. Redhu:Novartis: Employment. Corrado:Novartis Pharma AG: Employment. Binlich:Novartis Pharma SAS: Employment.

Abstract: Introduction: Panobinostat (PAN) is a potent pan-deacetylase inhibitor (pan-DACi) that targets key aberrations in multiple myeloma (MM) cell biology, including protein metabolism and epigenetics. In a randomized phase 3 clinical trial in patients (pts) with relapsed or relapsed and refractory MM (PANORAMA 1), the addition of PAN to bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) led to a clinically relevant and statistically significant increase in progression-free survival (PFS) of ≈ 4 months compared to placebo plus BTZ and Dex (Pbo-BTZ-Dex). PAN-BTZ-Dex was associated with a higher rate of adverse events (AEs) compared to Pbo-BTZ-Dex; however, a comparable number of pts completed the full duration of treatment on both treatment arms. Thus, we sought to determine the effect of treatment duration on the safety and efficacy of PAN-BTZ-Dex. Methods: The PANORAMA 1 trial consisted of two treatment phases (TP1 and TP2) with a maximum of 12 cycles total. In TP1 (eight 3-wk cycles), pts were randomized to receive oral PAN (20 mg) or Pbo administered three times a wk for the first 2 wks, and intravenous BTZ (1.3 mg/m2) administered on days 1, 4, 8, and 11 with Dex (20 mg) administered orally on the days of and after BTZ. Pts demonstrating clinical benefit could proceed to TP2 (four 6-wk cycles), in which PAN was administered on a similar schedule but BTZ was administered once-wkly (days 1, 8, 22 and 29) with Dex administered on the days of and after BTZ. This analysis focused on safety and efficacy specifically associated with the two treatment phases. For efficacy outcomes (PFS and near complete response/complete response [nCR/CR] rate), pt groups were delineated by those who received treatment 〉 8 cycles (completed TP1, 24 weeks) and all 12 cycles (completed TP2, 48 weeks). Median PFS was calculated based on time averaged dose (cumulative dose in a time interval divided by the planned number of dosing days) of PAN received to determine the potential role of dose adjustments/interruptions on efficacy. PFS was analyzed by Kaplan-Meier estimates. A safety analysis was conducted of AEs for TP1/TP2 for pts who completed TP2. Due to interdependencies among outcomes, further investigations of these data are needed. Results: Among the pts enrolled in the PAN-BTZ-Dex arm (N = 387), 169 (44%) completed TP1 and 102 (26.4%) completed TP2. Overall, pts who received a longer duration of treatment with PAN-BTZ-Dex demonstrated a longer PFS (Figure). Median PFS for pts who received PAN-BTZ-Dex and completed TP1 was 14.65 months (95% CI, 12.94, 16.85) and 17.64 months (95% CI, 15.90, 20.07) for those who completed TP2. In addition, nCR/CR rate was 52.9% for pts who completed TP2. Overall, the rates of commonly observed grade 3/4 AEs (≥ 20%) in the PAN-BTZ-Dex arm were thrombocytopenia (TCP, 57.0%), diarrhea (25.5%), and asthenia/fatigue (23.9%). Safety analysis for pts who completed TP2 demonstrated the higher rate of AEs in TP1 vs TP2 (excluding AEs that continued from TP1). For pts in the PAN-BTZ-Dex arm who completed treatment (n = 102), the rates of grade 3/4 events in TP1 and TP2 for common AEs were TCP (47.1% and 5.9%), diarrhea (25.5% and 8.8%), and asthenia/fatigue (19.6% and 5.9%). For pts in the Pbo-BTZ-Dex arm who completed treatment (n = 102), the rates for TP1 and TP2 were TCP (10.8% and 1.0%), diarrhea (5.9% and 0%), and asthenia/fatigue (7.8% and 0%). About half the pts (218/387; 56.3%) in the PAN-BTZ-Dex arm did not enter TP2 (112/218; 51.4% discontinued to due AEs). Analysis of time averaged dose of safety set pts on the PAN-BTZ-Dex arm demonstrated a median PFS of 12.71 (95% CI, 10.58, 14.19) months for pts who received 〉 15-20 mg of PAN and 10.90 months (95% CI, 8.08, 12.71) for 〉 10-15 mg. Conclusions: These data highlight the PFS and nCR/CR rate among pts able to complete TP2 with PAN-BTZ-Dex. Furthermore, for pts who completed the entire treatment regimen, the incidence of new/worsening AEs in TP2 where BTZ was administered on a once weekly schedule was decreased. Pts who received a lower time averaged dose due to dose adjustments/interruption of PAN had a similar median PFS to pts who received a time averaged dose closer to the planned dose. Together, these data support the hypothesis that optimal management of AEs for pts receiving PAN-BTZ-Dex via dose adjustments including BTZ and/or concomitant medications, particularly earlier during their course of therapy, could increase treatment duration and maintain outcomes. Figure 1 Figure 1. Disclosures San Miguel: Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees. Jedrzejczak:Amgen, Novartis : Consultancy, Research Funding. Guenther:Novartis: Consultancy, Research Funding. Siritanaratkul:Novartis: Research Funding; Roche: Research Funding; Janssen: Research Funding. Schlossman:Millennium: Consultancy. Hou:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Onyx: Consultancy; Sanofi: Consultancy. Sopala:Novartis Pharma AG: Employment. Redhu:Novartis : Employment. Paul:Novartis: Employment. Corrado:Novartis Pharma AG: Employment. Binlich:Novartis Pharma SAS: Employment. Richardson:Takeda: Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees.

Abstract: Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, −2.33 ± 0.7 mg Fe/g dry weight [dw] , P = .001, and −4.18 ± 0.69 mg Fe/g dw, P 〈 .001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM −235 and −337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P 〈 .001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo.

Abstract: Benefit from panobinostat-dexamethasone-bortezomib was greatest in patients who received ≥2 prior regimens including bortezomib and IMiDs.

Abstract: Abstract 1629 Rituximab and chemotherapy induction followed by maintenance rituximab is the backbone of therapy for FL. IV rituximab administration can take several hours; therefore, a SC formulation has been developed which may shorten administration times and increase convenience for pts. Achieving clinically effective rituximab serum concentrations is essential for optimal activity (Yin et al, ASCO 2010, abstract e13108). Therefore, achieving non-inferior Ctrough levels with SC compared with IV dosing is expected to provide comparable efficacy. BO22334 (NCT01200758) is a two-stage, phase III, international, randomized, controlled, open-label study of SC vs IV rituximab combined with up to 8 cycles of CHOP or 8 cycles of CVP chemotherapy followed by maintenance in pts with previously untreated FL. Pts were scheduled to receive 8 cycles of rituximab, regardless of the number of chemotherapy cycles. In the SC arm, rituximab was administered IV (375 mg/m2) for the first cycle, with following cycles administered SC (1400 mg). Stage 1 aimed to confirm that the SC rituximab dose of 1400 mg (dose based on phase I study BP22333; Salar et al, EHA 2012, abstract 0794), resulted in non-inferior Ctrough rituximab levels compared with the 375 mg/m2 IV dose when given as 3-weekly induction therapy combined with chemotherapy. The stage 1 primary endpoint was non-inferiority of the Ctrough,SC:Ctrough,IV ratio (limit for non-inferiority was Ctrough ratio 〉 0.8) at Cycle 7 of induction. Secondary endpoints included comparisons of SC vs IV: area under the serum concentration–time curve (AUC); end of induction ORR; CR (CR/CRu); and safety. Previously untreated pts with histologically confirmed CD20-positive grade 1, 2, or 3a FL requiring treatment (N = 127) were randomized 1:1 to SC (n = 63) or IV (n = 64) rituximab, stratified by Follicular Lymphoma International Prognostic Index score, chemotherapy, and region. Allocation to R-CHOP or R-CVP was at the investigator's discretion; 40 pts in each arm (63%) received CHOP chemotherapy and the remaining pts (37%) received CVP chemotherapy. The primary PK endpoint was met with a geometric mean of 134.6 μg/mL for the rituximab SC arm (n = 48) and 83.1 μg/mL for the rituximab IV arm (n = 54) resulting in an SC:IV ratio of 1.62 (90% confidence interval [CI]: 1.36, 1.94). The Ctrough achieved with SC rituximab was therefore concluded to be non-inferior to IV administration. The geometric mean ratio of AUCSC:AUCIV (1.378 [90% CI: 1.241, 1.530] ) was also non-inferior. After a median follow-up of approximately 9 months, the overall safety profile was as would be expected for IV administration, with no new or unexpected adverse events (AEs). In the SC and IV arms AEs were experienced by 92% (n = 57) and 88% of pts (n = 57), respectively. Grade 3/4 AE were observed in 47% of pts in the SC arm and 46% in the IV arm. The only grade 3/4 AE occurring in 〉 10% of pts was neutropenia (26% in the SC arm, 22% in the IV arm) which was not associated with increased infection rate (grade 3/4 infections and infestations: 5% SC vs 9% IV). Total administration-related reactions (ARRs; any events occurring during/within 24 hours of drug administration that were considered treatment-related by the study investigator) were higher in the SC vs IV arm (50% vs 32%) with the majority being grade 1/2; there were no grade 4 ARRs. Individual ARRs (all grades) occurring in ≥5% of pts in the SC vs IV arms were: erythema (8% vs 3%), pruritus (6% vs 3%), chills (3% vs 6%), injection site erythema (10% vs 0%), and vomiting (3% vs 6%). Investigator-assessed ORR was 90.5% (95% CI: 80.4, 96.4) in the SC arm and 84.4% (95% CI: 73.1, 92.2) in the IV arm. Complete response (CR/CRu) rates were 46.0% (29/63 pts, 95% CI: 33.4, 59.1) for the SC arm and 29.7% (19/64 pts, 95% CI: 18.9, 42.4) for the IV arm. Stable and progressive disease rates were similar in each arm. An independent review of response assessments is planned. Data demonstrate PK non-inferiority and comparable efficacy for SC (1400 mg) compared with IV (375 mg/m2) rituximab administration, with similar ORR and CR rates in the rituximab SC and IV arms. Overall, SC and IV rituximab AE profiles were similar; ARRs were mostly of mild/moderate intensity. Stage 1 pts are continuing to receive maintenance treatment with SC or IV rituximab. Stage 2 of the study has opened recruitment of an additional 280 pts who will be randomized to receive SC (1400 mg) or IV rituximab. Disclosures: Davies: Roche: Consultancy, Honoraria, Research Funding. Off Label Use: Pharmacokinetics (PK), safety and overall response rate (ORR) achieved with subcutaneous (SC) administration of rituximab in combination with chemotherapy were comparable to those achieved with intravenous (IV) administration in patients (pts) with follicular lymphoma (FL) in the first-line setting. Siritanaratkul:Roche: Research Funding. Solal-Céligny:Roche, France: Consultancy, Honoraria, Research Funding. Boehnke:F. Hoffmann-La Roche: Employment. Berge:Roche: Employment. McIntyre:Roche: Employment. Barrett:Roche: Employment. Macdonald:Roche, Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: Background Thalassemia syndromes are the most common hereditary hemolytic anemia worldwide. Since 2013, Thalassemia International Federation (TIF) has launched new standard clinical practice guidelines (CPG) for non-transfusion dependent thalassemia (NTDT) and transfusion dependent thalassemia (TDT). Based on these guidelines, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications in order to early detect such complications for a proper clinical management. At present, there is no data in Thailand to show that how physicians are treating thalassemia patients especially on early detection of all complications and whether their real life practice has changed to follow those of both guidelines. Objectives To evaluate the performance of routine care, in terms of surveillance for thalassemia related complications and their prevalence in adult thalassemia patients during 2 periods; before and after 2 CPG were published. Methods In this retrospective study, we analyzed data from 3,233 adult thalassemia patients who were diagnosed and treated at our clinics at Department of Medicine, Siriraj hospital during 1994-2017. We divided them into 2 groups; those who have been treated and followed-up for 3 consecutive years during 2012-2014 and 2015-2017 (a period before and after the implement of CPG, respectively). Clinical data and laboratory results were collected. Complications were recorded including iron overload (IOL) (ferritin), transaminitis (ALT & gt;3x upper normal limit), diabetes mellitus (DM) or impaired fasting glucose (IFG)(fasting blood sugar), hypothyroidism (thyroid function test), low morning cortisol, vitamin D abnormality, viral infection (hepatitis B and C), osteopenia/osteoporosis (bone mineral density, BMD) and gallstones (ultrasonography or CT scan). To compare the performance of routine care from different treating physician groups, patients were categorized into 3 groups; those who attended thalassemia clinic (Thal) treated by mainly staffs and residents in hematology, those in private hematology clinic (Private) treated by mainly attending hematology staffs and residents in hematology, and those in internal medicine clinic (Non-hem) treated by internists and GP. Prevalence and surveillance rates for each complication between groups were analyzed by Independent t test (Chi-square or Fisher's exact test). This study was approved by local ethical committee. Results Total available 459 NTDT and 65 TDT adult patients were studied. Baseline characteristics were shown in Table 1. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). IOL is a complication that has been widely evaluated in all treatment groups (93.1%) followed by evaluation of liver function test (82.3%). However the rate of evaluation for other complications were significantly reduced and & lt;25% of patients were evaluated in several complications. This result suggests that the prevalence of thalassemia related complications might be underestimate the true prevalence and early detection of thalassemia related complications is still lacking. To test whether the implement of CPG has any impact on real-life clinical practice, we found that the rate of complication surveillance has increased significantly for several endocrine complications (DM/IFG, hypothyroid, adrenal insufficiency and low vitamin D) only in the group of patients treated at thalassemia clinic but not in others (Figure1). This suggested that CPG have yet to be implemented by those physicians and further endorsement is highly required. Conclusion This study was the first study that evaluated the real-world practical management of thalassemia patient in terms of complication surveillance. In our adult thalassemia population, thalassemia related complications were not uncommon and some occurred early in adulthood. Surveillance rates of these complications were low in all clinics. After implement of thalassemia CPG, the surveillance rates for complications were increased only in patients treated at thalassemia clinic but not in other two clinics. A two different standard of clinical practice even within the same tertiary care hospital such as Siriraj hospital has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand. Disclosures No relevant conflicts of interest to declare.