Abstract: Background: Rigosertib (RIG) is a Ras-mimetic that inhibits the PI3K and PLK cellular signaling pathways by binding directly to the Ras-binding Domain found in Ras effector proteins. It has been tested as a single agent in patients (pts) after failure of hypomethylating agents (HMAs). In vitro, the combination of RIG with azacitidine (AZA) inhibits growth and induces apoptosis of leukemic cells in a sequence-dependent fashion (RIG administered prior to AZA) (Skidan et al 2006). Phase I results of this study in pts with MDS or AML showed combination of oral RIG and standard-dose AZA to be well-tolerated with evidence of efficacy (Navada et al, Blood 2014). Phase II was initiated to further study the combination in pts with MDS. Methods: Results from pts in Phase II with MDS previously untreated with an HMA, or who had failed to respond to or progressed on a prior HMA, are presented, while response data from Phase I MDS pts are updated. Pts with CMML are analyzed separately. Oral RIG was administered twice daily on Day 1-21 of a 28-day cycle at the recommended Phase II dose (RPTD: 560 mg qAM and 280 mg qPM). AZA 75 mg/m2/d SC or IV was administered for 7 days starting on Day 8. A CBC was performed weekly and a bone marrow aspirate and/or biopsy was performed at baseline, day 29, and then every 8 weeks thereafter. Results: The combination of oral RIG and AZA has been administered to a total of 45 pts within Phase I (N=18) and Phase II (N=27). Pts were classified into the following MDS risk categories per the IPSS (Greenberg et al, Blood 1997): intermediate-1 (4), intermediate-2 (10), high-risk (14), and IPSS classification pending (4). Five pts had CMML and 8 had AML. Median age was 66 years; 69% of pts were male; and ECOG performance status was 0, 1, and 2 in 27%, 67%, and 6%, respectively. Twelve pts [MDS (9), CMML (3)] received prior HMA therapy: AZA (11 pts), decitabine (1 pts). Patients have received 1-21+ cycles of treatment to date (median, 3 cycles), with median duration of treatment of 14 weeks. Among 15 evaluable MDS pts treated with the RPTD (1 pt in Phase I, 14 pts in Phase II), marrow responses were observed in 10: marrow CR (mCR) (8), marrow PR (mPR) (2). Responses according to IWG criteria were observed in 10 pts: complete remission (CR) (1), mCR (7), hematologic improvement (HI) (2). Table 1. Responses for MDS Patients Treated at the Recommended Phase II Dose Pt Prior HMA Best BMBL at Nadir1 IWG Response2 Hematologic Improvement 102-008 None mCR mCR Platelet 101-010 None mCR CR Erythroid & Neutrophil 101-011 None mCR mCR None 101-013 None mCR mCR Erythroid 102-010 None SD SD None 101-014 AZA PD PD None 102-011 AZA mPR HI Erythroid & Platelet 101-016 AZA SD SD None 101-017 AZA mCR mCR None 102-013 None NE NE NE 101-019 None SD SD None 101-021 None PD PD None 101-024 None mCR mCR None 101-022 AZA mCR mCR None 101-025 None mCR mCR None 101-026 AZA NE NE NE 101-027 None NE NE NE 102-016 None mPR HI Platelet 1 Silverman et al, Hematol Oncol 2014 2 IWG = International Working Group (Cheson et al, Blood 2006) NE = not evaluable BMBL = bone marrow blast Overall, in pts with MDS treated on Phase I and Phase II, marrow responses were observed in 15 out of 20 evaluable pts: mCR (13), mPR (2). Responses according to IWG 2006 criteria were observed in 14 out of 19 evaluable MDS pts: CR (2), mCR (10), HI (2). Among the 7 evaluable pts with MDS in both the Phase I and Phase II who had failed to respond or progressed on prior treatment with an HMA, 5 had a response after RIG was added: CR (1), mCR (3), HI (1). Analyzed as a separate subgroup, 2 out of 5 (40%) pts with CMML had a mCR. The most frequent adverse events (AEs) in Cycle 1 included nausea (21%) and fatigue (15%), which were also the most frequent AEs in all cycles (fatigue, 28%; nausea, 26%). Six deaths have been observed so far. Three pts were treated for more than 1 year and continue on study. Conclusions: The combination oforalrigosertib and standard-dose AZA was well tolerated in repetitive cycles in pts with MDS. Marrow CR was observed in 65% of pts, both with de novo MDS and after failure of prior HMA therapy. In pts who received the RPTD, 67% of pts with MDS had a bone marrow blast and IWG response. These results suggest potential synergistic interaction of the combination and support continued study of this unique combination in patients with MDS. Disclosures Silverman: Onconova Therapeutics Inc: Honoraria, Patents & Royalties: co-patent holder on combination of rigosertib and azacitdine, Research Funding. Daver:ImmunoGen: Other: clinical trial, Research Funding. DiNardo:Novartis: Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Fenaux:CELGENE: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding. Fruchtman:Onconova Therapeutics Inc: Employment. Azarnia:Onconova Therapeutics Inc: Employment.

Abstract: Background: Based on a model suggesting leukemia can be driven by combined effect of mutations in an epigenetic gene (DNMT3) and Ras, the combination of a hypomethylating agent (HMA) such as azacitidine (AZA) and a Ras mimetic such as rigosertib (RIG) may have enhanced activity in both MDS and AML. The mechanism of action for RIG (Athuluri-Divakar et al, Cell 2016) documents its interference with the RAS-binding domains of RAF kinases and inhibition of the RAS-RAF-MEK and the PI3Ks pathways. In vitro, the combination of RIG with AZA was found to act synergistically to inhibit growth and to induce apoptosis of leukemic cells in a sequence-dependent manner (exposure to RIG first, followed by AZA) (Skidan et al, AACR 2006). Rigosertib's low bone marrow toxicity in pre-clinical assays, effective inhibition of human hematopoietic tumor cell lines, and its synergy with AZA suggests the potential value of combination treatment for patients (pts) with MDS. Phase I results of the current clinical study in pts with MDS or AML showed the combination of oral RIG and standard-dose AZA to be well-tolerated with evidence of efficacy (Navada et al, Blood 2014). The phase II portion of the study was initiated to further evaluate the combination in pts with MDS. Methods: Phase II results are presented for HMA-treatment-naïve MDS pts and for those with MDS failing to respond to or progressed on a prior HMA. Oral RIG was administered twice daily on Day 1-21 of a 28-day cycle at the recommended Phase II dose (RPTD: 560 mg qAM and 280 mg qPM). AZA 75 mg/m2/d SC or IV was administered for 7 days starting on Day 8. A CBC was performed weekly and a bone marrow aspirate and/or biopsy were performed at baseline, D29, and then every 8 weeks thereafter. Results: The combination of oral RIG and injectable AZA has been administered to a total of 54 pts, of whom 40 were pts with MDS including HMA-treatment-naïve (N=23) and previously HMA treated pts (N=17). Median age was 66 years (range 25-85); 73% of pts were male; and ECOG performance status was 0, 1, and 2 in 23%, 73%, and 5%, respectively. 17 pts received prior HMA therapy: 12 AZA, 4 decitabine, and 1 both. Patients have received 1-36+ cycles of treatment (median, 6 cycles), with a median duration of treatment of 25 weeks (range 4 to 145+ weeks). 8 (20%) and 2 (5%) of pts have been treated for more than 1 and 2 years, respectively. Table 1 shows the response per IWG 2006 criteria (Cheson, Blood 2006) among 33 evaluable patients. The response per IWG 2006 was complete remission (CR) in 8 (24%), concurrent marrow CR and hematologic improvement (HI) in 9 (27%), marrow CR alone in 7 (21%), and HI alone in 1 (3%). When overall response is defined as CR plus PR plus HI - responses with improvement in marrow function and thus either normalization of the peripheral blood count or lineage improvement - defined here as Clinical Benefit Response - 55% of all evaluable pts and 70% of the evaluable HMA-treatment-naïve patients showed responses meeting these criteria. Median time to initial response was 2 cycles (2.2 months), and median time to best response was 3 cycles (3.3 months). Median duration of response was 8 months for CR, 14.3 months for marrow CR, 7.4 months for erythroid response, 8 months for platelet response, and 6.2 months for neutrophil response. Clinical response is classified by IPSS-R risk categories below. The most frequently reported adverse events are nausea (41%), fatigue (39%), diarrhoea (37%), constipation (37%), dysuria (28%), decreased appetite (28%), haematuria (24%, 8% Grade 3), pyrexia (24%), dizziness (22%), thrombocytopenia (20%), back pain (20%), dyspnoea (20%), and cough (20%). Eight deaths were reported on study with most common causes including infection and progression of disease. Conclusions: The combination oforalRIG and standard-dose AZA was well tolerated in repetitive cycles in pts with MDS. Response per IWG 2006 criteria was observed both in HMA-treatment-naïve patients (85%) and in patients after failure of prior HMA therapy (62%); employing Clinical Benefit Response as the criteria, these groups had 70% and 31% response, respectively. These clinical results confirm the preclinical synergistic interaction with the combination of RIG and AZA reported by Skidan et al, and suggest that the combination can overcome clinical resistance to HMAs. Based on these results, a Phase III study of the combination of oral RIG and AZA in patients with MDS is planned. Disclosures Navada: Onconova Therapeutics, Inc.: Research Funding. Daver:Karyopharm: Honoraria, Research Funding; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Ariad: Research Funding; Otsuka: Consultancy, Honoraria; Kiromic: Research Funding; BMS: Research Funding. DiNardo:Agios: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Fenaux:Celgene, Janssen,Novartis, Astex, Teva: Honoraria, Research Funding. Petrone:Onconova Therapeutics, Inc.: Employment. Zbyszewski:Onconova Therapeutics, Inc.: Employment. Fruchtman:Onconova: Employment. Silverman:Onconova Therapeutics, Inc.: Patents & Royalties: Co-Patent holder for the combination of azacitidine and rigosertib, Research Funding.

Abstract: Abstract 1750 The Myeloproliferative Disorder-Research Consortium (MPD-RC) designed the first US prospective phase II study of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary myelofibrosis (PMF) or MF secondary to essential thrombocythemia (ET-MF) or polycythemia vera (PV-MF). Between May 2007 and March 2011, 66 patients were entered into the MPD-RC 101 study. Thirty-two patients received an allogeneic HSCT from a related and 34 patients from an unrelated donor. In the two groups diagnoses were: PMF: 44%, 74%; ET-MF: 47%, 12% and PV-MF: 9%, 15%, respectively. A reduced intensity regimen with fludarabine/melphalan (FluMel) ± ATG was used. Of 66 patients, 63 were at intermediate/high risk according to Lille score system and 3 patients were at low risk but had thrombocytopenia. Recipients of related and unrelated HSCT were comparable with respect to age (median: 54 vs 55 years), gender (M/F 19/13 vs 19/15), Lille score intermediate (63% vs 68%) or high risk (28% vs 32%) and time from diagnosis to transplant (median, range: 16, 1–247 vs 20, 2–341 months). At the time of transplant, 66% and 82% of patients in the related and unrelated cohorts had splenomegaly and 19% and 15% had previous splenectomy. Jak-2 V617F mutation was present in 38% and 50% and an abnormal karyotype was detected in 56% and 59% of patients with known status, respectively. Bone marrow stem cells were utilized in 19% of related and 9% of unrelated transplants, while in the remaining cases patients received peripheral blood stem cell (PBSC) grafts. Donor compatibility was assessed by molecular typing for HLA A, B, C, DRB1 and DQB1 antigens; inclusion criteria allowed enrollment with maximum 1 antigen mismatched donor. Thirty of 32 transplants (94%) in the related cohort and 25/36 (74%) in the unrelated cohort were fully matched. In transplants from related donor, engraftment of neutrophils and platelets occurred in 31/32 patients, One patient in this group experienced a secondary graft failure. In contrast, among patients in the unrelated group only 26/34 (76%) patients engrafted and of these 4 had a secondary graft failure post transplant. Median time to neutrophils 〉 0.5 × 109/L and platelets 〉 20 × 109/L engraftment was: day 22 and day 28 in the related, and day 18 and day 28 in the unrelated cohort, respectively. Acute GVHD grade II-IV was observed in 37% related (grade III-IV: 12%) and in 42% unrelated transplants (grade III-IV: 21%). Based on the International Working Group criteria, in patients who were followed for at least 6 months there were 7 CR, 8 PR, and 11 CI among the 28 patients in the related group, and 5 CR, 1 PR, and 5 CI among the 16 patients in the unrelated group. After a median follow-up for survivors of 24 months, 25 patients (78%) in the related group are alive, 6 patients (18%) died for causes related to transplant (GVHD n=3, cardiac toxicity n=1, renal failure n=1, secondary cancer n=1) and 1 (3%) for progression of disease. In the unrelated group, 15 patients (44%) are alive at 12 months follow-up for survivors, 18 patients (53%) died for causes related to transplant and 1 patient (3%) due to relapse. Median survival time has not been reached in the related transplant group and is 7 months in the unrelated group (hazard ratio 4.2, 95% CI: 1.7–10.1, p 〈 0.001). Survival in unrelated transplants was not associated with HLA matching, diagnosis, or the presence of Jak-2 mutation. In this prospective study a reduced intensity allogeneic HSCT with Flu/Mel regimen was very effective in patients with myelofibrosis transplanted from related donors. In unrelated transplants, a high rate of primary or secondary graft failure led to a high rate of transplant-related-mortality. For these patients a different conditioning regimen may be required. Disclosures: No relevant conflicts of interest to declare.

Abstract: PURPOSE: Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS. PATIENTS AND METHODS: A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m 2 /d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C. RESULTS: Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P 〈 .001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P = .007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P = .001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P = .03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C. CONCLUSION: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.

Abstract: The International Prognostic Scoring System (IPSS) requires cytogenetic data to evaluate risk in MDS. Cytogenetic data were not available for all patients from the CALGB trial 9221 (Silverman et al, JCO2002; 20:2429). Therefore, we developed an alternative prognostic model that identified a homogeneous subgroup of high-risk MDS patients based on the following risk factors: percent marrow blasts, number of cytopenias, age, gender, FAB classification, and time since diagnosis (IPSS used data at time of diagnosis; CALGB 9221 used data at time of randomization). The model was validated using 2,318 patients from the MDS Registry, Düsseldorf. Using these baseline prognostic factors, we predicted survival for each of the 191 CALGB patients, identified a high-risk subgroup with a survival prognosis of ≤ 1.2 years (the IPSS INT-2 survival median), and compared azacitidine to supportive care. Patients were analyzed as randomized (azacitidine or supportive care) according to the intention-to-treat (ITT) principle. The two groups had similar demographic and disease characteristics. All 70 high-risk patients were followed until death. There was a statistically significant difference in overall survival curves between the azacitidine and supportive care groups (p=0.03). The one-year survival rate was 63% (95% CI: 47 to 78%) in the azacitidine group and 37% (95% CI: 19 to 54%) in the supportive care group (p=0.03; 26% difference with a 95% CI of 3 to 49%). The two-year survival rate was 35% (95% CI: 20 to 50%) in the azacitidine group and 13% (95% CI: 1 to 25%) in the supportive care group (p=0.03; 22% difference with a 95% CI of 3 to 41%). Similarly, statistically significant differences in time to AML transformation, and death or AML transformation, were observed. Transfusion independence was defined as free from transfusions for at least 2 months. Among patients who were RBC transfusion dependent at baseline, a significantly greater number of patients from the azacitidine group (11/25, 44%) compared with patients from the supportive care group (1/14, 7%) achieved transfusion independence (p=0.03; 37% difference with a 95% CI of 7 to 59%). Additionally, patients in the azacitidine group with baseline transfusion independence experienced significantly prolonged duration of RBC (p & lt;0.0001) and platelet (p=0.0002) transfusion independence compared with those in the supportive care group. Use of this prognostic model has identified a subgroup of high-risk MDS patients who significantly benefited from treatment with azacitidine. Time of Even Analysisa

Abstract: The prognosis for patients with refractory anemia with excess blasts (RAEB) or RAEB in transformation (RAEB-T) ≥ 65 years of age has been poor. These high-risk patients are often not eligible for intensive induction/transplantation regimens or combination chemotherapies, leaving few treatment options besides supportive or palliative care. In the publication of the CALGB trial by Silverman et al (JCO2002;20:2429), no age- and/or risk- related subgroup analyses for azacitidine (Vidaza®) were presented. To assess the treatment effect of azacitidine versus supportive care on survival and time to AML transformation in a homogeneous sample of high-risk patients with MDS, we performed a subgroup analysis on the 191 patients included in the CALGB trial. All patients with a baseline diagnosis of RAEB or RAEB-T who were ≥ 65 years of age were included in the comparative analysis, using intent-to-treat (ITT) principles based on randomization to azacitidine or supportive care. Efficacy was analyzed using three survival endpoints: overall survival, time to death or AML transformation, and time to AML transformation. In all, 31 azacitidine patients and 37 supportive care patients met the criteria for this high-risk subgroup analysis. No significant differences in demographics or disease characteristics between the two groups were observed. For all three survival analyses, a statistically significant difference was observed for patients in the azacitidine group compared with those in the supportive care group. (Table) Median time to transformation to AML, in particular, was prolonged for 24 months in azacitidine patients compared with patients in the supportive care group. A sensitivity analysis of the overall survival results was conducted by performing 10 additional subgroup analyses based on ages ≥ 60 through ≥ 70 years in increments of one year with all overall survival results remaining significant (p & lt; 0.05, except for 2 subgroup analyses based on ages ≥ 60 and ≥ 66 where both p-values were 0.051). The sensitivity results demonstrated robust patient benefit in the subgroup ≥ 65 years of age. The most common adverse event observed with azacitidine was myelosuppression, which decreased in frequency as therapy continued. Azacitidine provided clear treatment effect and patient benefit to this difficult-to-treat, high-risk group of RAEB and RAEB-T patients ≥ 65 years of age by significantly prolonging overall survival and time to AML transformation. Time of Even Analysis

Abstract: Background: Myelodysplastic Syndrome (MDS) and Aplastic Anemia (AA) are often associated with clinical immune manifestations. An abnormal profile of the T-cell repertoire can be detected in these patients (pts) and is thought to play a role in bone marrow (BM) insufficiency. The presence of a co-existent large granular lymphocytic (LGL) clone may exacerbate cytopenias independent of the primary disease mechanism and offers another target for therapeutic intervention. Treatment for LGL proliferation is usually immunosuppressive therapy but there is no accepted standard of care. Methods: We explored the role of intravenous immunoglobulin (IVIG) as a treatment for immune-related cytopenias, i.e. Coombs negative (C-) hemolytic anemia, in a series of 12 consecutive pts with an LGL clonal proliferation documented by flow cytometry and TCR clonal rearrangements. Of the 12 cases, 9 had MDS (7 lower-risk), 1 AA with LGL liver involvement, and 1 primary myelofibrosis. One patient (pt) had suspected MDS. Overall response was assessed by MDS IWG criteria 2006. We defined a hemolysis response (HLR) as complete normalization (CR) or, a greater than 50% improvement (PR) in deviation from normal values of LDH, reticulocytes, indirect bilirubin and haptoglobin. Duration of HLR was defined as the time from onset of HLR to the time of resumption of hemolysis and loss of effect of IVIG. Results: All pts were treated with IVIG administered at a dose of 500mg/kg of IVIG once per week, in repeated cycles, with a duration ranging from 1-4 week(s) per cycle. Clinical characteristics (Table 1): M/F ratio 10/2; median age 69. Ten pts had a CD3+ T-LGL and 2 had a CD3-/CD16+/CD56+ NK-LGL circulating clone. Karyotype abnormalities were non-specific; 8 pts had 1-3+ reticulin BM fibrosis; 4 had mutations in RNA-splicing genes: SF3B1 (2); SETBP1 (1); SRSF2 (1). Ten pts were evaluable for response: 8 pts responded (ORR 80%): Hematological improvement (HI-erythroid) 8/8 (100%); a hemolysis CR (HLR-CR) occurred in 7 (87.5%) and hemolysis PR (HLR-PR) in 1 pt (12.5%). Median number of cycles, follow up, and duration of treatment were 16, 21.5 and 9.5 months (mo), respectively. The HLR-CR was durable and prolonged in 3/8 (38%) pts; 2 of these 3 pts (67%) did not require maintenance IVIG. Relapse from HLR occurred in 4, during infection or chemotherapy, but the response returned to the original level by shortening the intervals between administration of IVIG. One pt had relapsed after an initial response and then became refractory to IVIG. In follow up at month 38, 75% of pts were still responding to treatment, and 1 pt was still in remission after 46 mo. In 4 of 6 pts, corticosteroid treatment was discontinued and no longer required for chronic hemolysis, with general improvement of steroid related symptoms. Some patients had been on steroids maintenance for periods ranging from months to years. Response was more durable with continuous rather than sporadic dosing. Adverse events were not specific: 1 pt with self-limited isolated palpitations; 1 pt with hypertension not requiring intervention. Conclusions: Treatment with IVIG of immune cytopenias associated with LGL clones and BMF yields durable responses in 80% of pts. IVIG, especially at high concentrations, may enhance apoptosis, suppress proliferation of T-cells and induce immune-regulation. Given the relative rarity of LGL clones in MDS, further investigational studies will help define the role of IVIG and clarify the mechanism of action in this group of pts with MDS and BMF associated with LGL clones. Table 1. Variable Observed % Symptomatic anemia (fatigue, SOB) 9/12 75 B symptoms (recurrent fever) 2/12 16.6 Infections (bacteremia Campylobacter with migratory arthritis and dermatitis; cellulitis bacteremia S. epidermidis and osteomyelitis) 2/12 16.6 Skin lesions (leg focal ulceration and dermal fibrosis) 1/12 8.3 Splenomegaly 7/12 58.3 Hepatomegaly 2/12 16.6 Adenopathy (mediastinal) 1/12 8.3 Neuropathy 2/12 16.6 Hematologic disorders 11/12 91.6 Myelodysplastic syndrome 9/12 75 Severe aplastic anemia 1/12 8.3 Myeloproliferative neoplasm (PMF) 1/12 8.3 Lymphoproliferative neoplasm (FL+MDS) 1/12 8.3 Hemolytic anemia 11/12 91.6 Solid tumors (anal, squamous cell; breast ca) 2/12 16.6 Autoimmune disorders 7/12 58.3 ITP 3/7 42.8 Ulcerative colitis 1/7 14.3 Pernicious anemia 1/7 14.3 Systemic lupus erythematosus 1/7 14.3 Immune pancreatitis 1/7 14.3 MGUS 4/12 33.3 Disclosures Off Label Use: IVIG.