ALBERT

Description: Abstract 3842 Background: Dysregulated JAK-STAT signaling is a key feature in MF, which is characterized by splenomegaly, debilitating symptoms, poor quality of life (QoL), cytopenias, and shortened survival. Ruxolitinib is a selective JAK1 and JAK2 inhibitor with clinical activity in MF. COMFORT-I is a Phase III, double-blinded, placebo-controlled study of ruxolitinib in patients with MF. At wk 24, 41.9% of patients receiving ruxolitinib reached the protocol-defined threshold of a ≥35% reduction in spleen volume (SV) compared to 0.7% in the placebo group (p200 x109/L. SV was measured by blinded imaging (MRI or CT scan) every 12 wks. Via electronic diary, patients reported MF symptoms daily using the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0. The Total Symptom Score (TSS) from the MFSAF represents a combined score for the individual symptoms of abdominal discomfort, pain under ribs on left side, early satiety, itching, night sweats, and bone/muscle pain. The European Organization for Research and Treatment of Cancer Quality-of-Life 30 (EORTC QLQ-C30) and Patient-Reported Outcomes Measurement System (PROMISE) Fatigue questionnaires were administered at each visit; Patient Global Impression of Change (PGIC) was administered at every visit beginning at wk 4. The PGIC rates a patient's overall sense of whether a treatment has been beneficial or not on a 7-point scale, ranging from 1 = very much improved to 7 = very much worse, with 4 = no change. Results: Baseline QoL scores reflected debilitating disease, and were similar to scores for similar-aged patients with other cancers (Scott NW, Fayers PM, Aaronson NK, et al. EORTC QLQ-C30 Reference Values Manual, July 2008). The impact on patients was particularly evident on the PROMIS Fatigue scale and QLC-C30 Global Health, Physical Functioning, Role Functioning, and Social Functioning subscales. Baseline Symptom and QoL Measures* Associations between changes in symptoms and QoL with the objectively measured changes in SV were evaluated. Patients receiving ruxolitinib were grouped according to SV reduction at 24 wks of treatment: ≥35% reduction in SV (n=65), 10-

Description: Combination therapy utilizing 2 novel agents with independent mechanisms of action and non-overlapping toxicities may be useful in the setting of advanced cancers. Tipifarnib (T) is an orally bioavailable farnesyltranferase inhibitor with documented single-agent activity in acute myeloid leukemia (AML). Bortezomib (B) is a broad inhibitor of proteasomal function, approved for treatment in multiple myeloma and mantle cell lymphoma. Preclinical studies indicated synergistic activity between these 2 agents for eliciting apoptosis within leukemia and myeloma cell lines and ex-vivo cells adhered to fibronectin. In this phase I combination trial, we studied the effect of combined effect of T plus B in patients with advanced acute leukemias. Objectives: The primary endpoint was toxicity assessment. Secondary endpoints included effect of combined therapy on signaling intermediates, including p-AKT, Bim, Bax, and NF-kB, as well as effects on farnesyltransferase (FT) and the proteasome activity. Eligibility: Patients with AML, ALL, or CML-BC who had received 〈 3 cycles of prior therapy were eligible. Methods: Patients received T on days 1–14 and B on days 1, 4, 8, and 11. Cycles were repeated every 21 days. Dose escalation occurred using cohorts of 3–6 patients. The starting dose was T: 300 mg/m2 and B: 1.0 mg/m2 Bone marrow aspirate was obtained at baseline, day 8, and between day 15 and the start of the next cycle. Measurement of signaling intermediates were performed in Ficoll-enriched leukemic marrow blasts using Western Blot (p-AKT, Bax, Bim) and ELISA (NF-kB). FT and proteasomal activity were directly measured within peripheral blood mononuclear cells (PBMC) using previously described methods. Results: To date, 27 patients have been enrolled at 3 centers. Four patients were ineligible after screening, and 23 patients have been treated. Median age was 69 years (range 48–84) Diagnosis: AML=25, ALL=1, MDS=1. Accrual to the 4th and final dosing cohort has occurred, without maximum tolerated dose being reached at the 4th and final planned dosing cohort (T: 600 mg/m2 and B: 1.3 mg/m2). Six patients received ≥ 2 cycles of treatment. Dose-limiting toxicities to date have included: nausea/diarrhea (1 patient), sensory neuropathy (1 patient), and fatigue (1 patient). Common drug-related (〉 10%) non dose-limiting toxicities included: infection/febrile neutropenia, diarrhea, nausea, vomiting, sensory neuropathy, and fatigue, most of which were grade 1 or 2. FTase inhibition within peripheral blood mononuclear cells (PBMC) was measured serially in 8 patients to date, with a median of 70% inhibition by day 8, and with 5 out of 6 evaluable patients having sustained inhibition at day 22. Proteasome function within PBMCs was reduced by a median of 44.3% in 7 patient samples pre-infusion and 1 hour post-infusion on day 8. Proteasome activity within PBMCs at day 22 was decreased from baseline in 5 out of 7 patient samples tested. Compared to baseline, NF-kB binding activity within leukemic blasts at day 8 was decreased by a median of 39% at in 10 out of 14 paired samples. No significant change in expression of p-AKT, Bax, or Bim, as measured by Western Blot, was detected at day 8. Two patients achieved clinical response; 1 patient had a complete response and another patient had complete response with incomplete count recovery. Four others had stable disease following cycle 1. Conclusion: combined therapy with T + B was well tolerated and demonstrated inhibition of several relevant target signals within leukemic blasts and PBMCs. In addition, clinical activity was seen in 2 patients to date. Accrual to the trial is ongoing and updated clinical and pharmacodynamic data will be presented.

Description: Background: T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in adults is an aggressive bone marrow malignancy that historically has a poor prognosis. Hyper-CVAD/methotrexate-cytarabine (hyper CVAD) regimen is a commonly used induction regimen following the protocol developed at MD Anderson Cancer center. Recent reports from Swedish Cancer Registry showed that relapse rates were much higher than expected with this regimen. We report our retrospective experiences across three different centers, Winship Cancer Institute of Emory University (Atlanta), University of Alabama Cancer Center (Birmingham) and Moffitt Cancer Center, (Tampa), with the use of this regimen for management of T-ALL/LBL. Methods: We conducted a retrospective chart review of all adult T-ALL/T-LBL cases at three large cancer centers between the years 2005-2015, treated at the physician's discretion. Data collected included patient demographics, tumor characteristics (white count at diagnosis, flow cytometry, FISH, cytogenetics, bone marrow involvement), treatment regimens and patient outcomes. Since hyper CVAD is a commonly used regimen outside of clinical trials, we focused our analysis on outcomes with this regimen. This regimen consisted of 4 courses of hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone; the odd courses 1, 3, 5, 7); and 4 courses of MTX-Ara-C (methotrexate-cytarabine; the even courses 2, 4, 6, 8). CNS prophylaxis was given to all patients as per standard of care recommendations. All patients eligible for maintenance received 2 years of POMP (6 mercaptopurine, methotrexate, vincristine and prednisone) maintenance. Relapse-free survival (RFS) and overall survival (OS) were examined looking at medians and interquartile ranges of times to events. Kaplan Meier curves provided a graphical representation of the survival probability. Results: The final analysis included 95 adult patients with 64/95 (67%) patients receiving hyper-CVAD induction. Among the hyper-CVAD patients the median age at diagnosis was 30 (range 17-74). 71% of patients were male. Median white cell count (WBC) was 13.6/mm3 (1.7-500). Cytogenetic analysis revealed diploid in 36, complex (1 or more abnormalities in 16) and was not available in 12. WBC count was 〉 100,000/mm3 in 9 patients. 14 patients had mediastinal disease while 7 had CNS disease at diagnosis. Hyper-CVAD was the primary induction regimen in 56/64. Other patients either started on non-hyper CVAD induction prior to switching (n=3) or had asparaginase added to induction (n=5). The median number of cycles given as 7 (range 2-10) with 27(45%) patients receiving the planned 8 cycles. 37 patients did not complete 8 cycles due to stem cell transplant in remission (n=12), progressive disease (n=10) and unclear reasons (n=15). After induction therapy, remission status was unknown in 3 patients while 43/61 patients (70%) achieved remission. Maintenance with POMP was started in 21 patients that were in remission while 12 patients were taken to transplant without starting on maintenance. At the time of analysis, 23/64 (35%) patients are alive. The median relapse free survival was 387 days (12.9 months) and the median overall survival was 536 days (17.6 months). Excluding one patient lost to follow up, 44/63 (69.8%) relapsed. There was no difference in relapse versus non relapse patients in terms of median age (30 vs 33 years), median WBC at diagnosis (13.2 vs 13.6 mm3). Relapse rate was lower in patients with diploid karyotype (22/36, 61%) as compared to those with complex karyotype (14/16). Median survival in patients post relapse was 150 days. Only 9 patients were able to go for transplant after relapse with post transplant survival also being low (6 deaths). For the entire group, the two year survival was 35%. Conclusion: Our multi-institutional retrospective review shows that outcomes are poor across various centers in patients outside of clinical trials. This is the largest reported series of patients with adult T-ALL/T-LBL treated with hyper-CVAD outside of clinical trials. This data warrants investigation with newer agents to improve outcomes in this disease. Figure 1. Relapse free survival and overall survival in patients treated with hyper-CVAD (n=64) Figure 1. Relapse free survival and overall survival in patients treated with hyper-CVAD (n=64) Disclosures Kota: Leukemia Lymphoma Society: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Hathaway:OnQ Health: Research Funding. Shah:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acetylon: Membership on an entity's Board of Directors or advisory committees; PLexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria; Rosetta Genomics: Research Funding; Seattle Genetics: Research Funding. Jillella:Seattle Genetics, Inc.: Research Funding. Borate:Genoptix: Consultancy; Seattle Genetics: Research Funding; Gilead: Speakers Bureau; Alexion: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau.

Description: The second-generation TKIs (2G-TKIs) Dasatinib (DAS) and Nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) CML as compared to Imatinib (IM) however, long-term safety of these agents is a growing concern. We identified 10 patients with CP CML diagnosed between 08/2013 and 06/2015 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. DAS was administered to 8 patients at 100 mg/d and NIL in two patients at 300 mg twice a day. Response to TKI was assessed by quantitative reverse transcriptase polymerase chain reaction (qPCR) for BCR-ABL1. Response to 2G-TKIs after 3 months was as follows: CHR (n=10), 1 log (

Description: Abstract 2576 Cerebrospinal fluid (CSF) involvement by leukemic blasts occurs in fewer than 10 % of adult patients with newly diagnosed acute lymphoblastic leukemia/lymphoma (ALL). Leukemic meningitis is diagnosed by microscopic detection of blasts in the CSF. Flow cytometry is a highly sensitive tool for detection of aberrant cells. We sought to analyze the additional benefit flow cytometry might provide for the diagnosis of leukemic meningitis. Between 11/2007 and 8/2011, 80 patients were diagnosed with ALL and treated at Emory University. 800 CSF samples were available for analysis 80 of which were collected from a diagnostic lumbar puncture (LP), 689 from follow-up LPs and 31 from LPs obtained at the time of relapse. As shown in the table, flow cytometry confirmed the presence of leukemic blasts in one, four and five samples diagnosed with leukemic meningitis by cytology at diagnosis, different stages of treatment and relapse, respectively. One and three samples were positive for leukemic blasts by cytology but negative by flow cytometry during different treatment stages and relapse respectively. We conclude that flow cytometry provided no additional benefit to cytology in the diagnosis of leukemic meningitis. Table: CSF Cytology and Flow Cytometry in 80 Adult ALL patients: CSF samples New Diagnosis N=80 Induction/Consolidation/Intensification/Maintenance/Remission/Post-transplant N = 689 Systemic relapse N = 31 N Cytology N = 80 Flow cytometry N = 66 Cytology N = 689 Flow cytometry N = 188 Cytology N = 31 Flow cytometry N = 13 Negative 79/80 65/66 684/689 184/188 23/31 8/13 Positive 1/80 1/66∼ 5/689 4/188∼* 8/31 5/13∼** ∼ CSF samples positive by flow cytometry were also positive by cytology * One CSF sample was positive by cytology but negative by flow cytometry ** CSF flow cytometry was not done in 3/8 positive CSF samples by cytology Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Tyrosine kinase inhibitors (TKI) are overall well tolerated in chronic myeloid leukemia (CML) s, but more than 30% require dose reduction or change to another TKIs due to intolerance. Impact of TKI dose-reduction on outcomes in a "real world" setting is unknown, thus, we evaluated the characteristics and outcomes of chronic phase (CP)-CML patients who received doses of TKI lower than the label/FDA recommendation. Method: CP-CML with at least 12 months of follow-up, with ISBCR/ABL1 available after dose reduction were selected. Last TKI was defined as TKI which were taken at the last follow up visit or before disease progression to accelerated (AP) or blast phase (BP). FDA approved doses of imatinib (IM), dasatinib (DAS), nilotinib (NIL), bosutinib (BOS), and ponatinib (PON) were 400mg, 100mg, 600mg (300mg BID), 500mg, and 45mg, respectively . Results: Between January 2005 and April 2016, 173 CP-CML patients, started IM (75%), DAS (18%) NIL (5%) and PON, BOS on clinical trial in 2%. Overall Fifty-eight (33.5%) patients had TKI dose reduction. IM (n=15) dose was reduced to 75% (range, 25-75), DAS (n=15) to 50% (range, 20-80), NIL (n=15) to 50% (range, 13-67), BOS (n=15) to 80% (range, 40-80) and PON (n=15) to 33% (range, 33-67). Median age for patients that received dose-reduced TKI was 55 (range, 18-88), and 27% received 〉 3 prior TKIs. With a median follow up of 53.6 (range 13.4-183.7) months, only 1 progressed to AP, and none to BP. Overall 60% achieved MMR. Among 35 patients who achieved MMR before dose reduction, MMR was maintained in 25 (71.4%) for a median of 17.2 (2-97.9) months from dose-reduction. CMR was achieved in patients on a maintenance dose of IM, 100mg QD (n=8); DAS, 20mg QD (n=4); NIL 300mg QD (n=3) and BOS, 200mg QD (n=3). Conclusion: Similar to data reported from clinical trials, TKI dose reduction appears to be safe and associated with high response rates. This data confirms that the minimal effective dose for each TKI remains to be defined. Disclosures Heffner: Pharmacyclics: Research Funding; AbbVie: Research Funding; Millennium: Research Funding; Celgene: Research Funding. Jillella:Leukemia Lymphoma Society: Research Funding. Kota:Ariad Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Description: Background: APL is a highly curable malignancy with reported survival above 90% in many co-operative group studies. However these spectacular results are not evident in the general population. US SEER data and other population based studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be as high as 30%, leading to a considerably lower survival compared to clinical trials where ED is around 5-10%. Decreasing ED remains a global challenge and the highest priority at all leukemia treatment centers and will result in population wide survival in this most curable leukemia. We report results of our prospective trial using a set of simplified treatment guidelines along with expert support designed to decrease ED. Methods: A network of leukemia treatment centers was established in Georgia, South Carolina and neighboring states. An aggressive outreach effort was made by visiting most of the leukemia treatment centers to publicize the concept and educate treating physicians in the community about ED in APL. The protocol provides a simplified two page treatment algorithm that emphasizes quick diagnosis, prompt initiation of therapy and proactive and aggressive management of the major causes of death during induction. Expert and treating physician communication was established very early when a diagnosis of APL was suspected and was maintained until the completion of induction. Study was approved by local IRBs (if applicable) and funded by the Lymphoma Leukemia Society (LLS). Informed consent was obtained upon confirmation of a diagnosis of APL and there were no exclusion criteria. Patient accrual was initiated in July 2013 and continued till May 2016 when the accrual goal of 120 was met on an intent to treat basis. Statistics are descriptive. Results: Between 7/2013 and 5/2016, 120 patients were enrolled at 5 large leukemia centers (n=54, 45%) and 24 community hospitals (n=66, 55%). Only 3 hospitals treated more than 3 APL patients/year. Median age was 54 years (range 21-84 years). 68 were male. 84% were low risk (WBC 〈 10,000/mm3) and median WBC count was 4.3 (range 0.3-170,000/mm3). ATRA was initiated at suspicion of APL diagnosis in 100% of patients and was the only treatment in 2(1.5%) patients. Arsenic was combined with ATRA in 93 (81.5%) patients while the other 17% received chemotherapy. 15(13%) had bleeding complications at presentation. Treatment course was complicated by infection and differentiation syndrome (DS) in 31(28%) and 40(34%) patients respectively. There were 12 early deaths, of which 1 was a Jehovah's Witness who declined transfusions and 1 who enrolled 12 days after diagnosis while in multi-organ failure. Incidence of ED was 10/118 (8.5%). The cause of death was disseminated intravascular coagulation (DIC) (n=4), DS (n=2), infection (n=1), anemia (n=1), multi-organ failure (n=4). With a median follow-up of 10.6 months, 2 low risk patients relapsed: I due to non-compliance 1 year after diagnosis and 1 with CNS relapse 3 months after completing consolidation. With a median follow up of 320 days (range 1-965) overall survival (Figure 1) was 87%. There were four late deaths; relapse (n=1), second cancer (n=1) and non-APL related comorbidities (n=2). Conclusions: Results of this prospective trial showed that a simplified treatment algorithm along with support from experts and co-management with treating physicians in the community decreased induction mortality (8.5%) and improved survival (87%) compared to SEER data (1 year relative survival of 71%). We believe our experience warrants large scale implementation and is presently approved as an ECOG/ACRIN trial (EA9131). This model can be applicable to other cancers and life-threatening diseases. Figure Overall Survival Figure. Overall Survival Disclosures Jillella: Leukemia Lymphoma Society: Research Funding. Heffner:AbbVie: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Millennium: Research Funding. Stuart:Astellas: Research Funding; Celator: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Agios: Research Funding; Bayer: Research Funding; Incyte: Research Funding. Gerber:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding. Grunwald:Medtronic: Equity Ownership; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Amgen: Research Funding; Janssen: Research Funding. Kota:Pfizer: Membership on an entity's Board of Directors or advisory committees; Ariad Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

Description: Advanced myelodysplastic syndrome and secondary or relapsed AML are difficult to treat, with CR rates following standard induction chemotherapy below those for de novo AML. We are examining a novel induction approach using the anti-CD33-calicheamicin conjugate gemtuzumab ozogamicin (GO) in combination with conventional chemotherapy. Methods and Patient Population: We present data from an ongoing phase I/II study, demonstrating the activity and tolerability of the combination in patients with MDS and AML. 32 pts (19 pts from phase I, 13 from phase II) were assigned to receive cytarabine 2 g/m2 over 4 hours once daily, and Topotecan 1.5 mg/m2 by continuous infusion daily on days 1–5. GO was then given on day 6 at a dose of 3 mg/m2 (7 pts), 4.5 mg/m2 (16 pts), or 6 mg/m2 (7 pts); 2 additional pts did not receive the GO because of intercurrent events. The MTD of GO was established at 4.5 mg/m2, which was used in phase II. The study population consisted of 13 pts with advanced MDS (IPSS 2–3), 13 pts with secondary AML, and 6 pts with relapsed AML. Median age was 64 (34–77). Results: ATGO was generally well tolerated. Bacterial infections, including 9 bacteremic episodes, were the most common non-hematologic complications. Two cases of reversible but unexplained grade 3 delirium were seen at 6 mg/m2 GO, meeting study criteria for dose-limiting toxicity. Only one case (3%) of clinical venoocclusive disease (VOD/SOS) occurred, in the single subject who received a second (half) dose of GO on day 16. Asymptomatic grade 3 hepatic transaminase elevations occurred in 8 pts (25%). There were 4 deaths (12.5%) prior to day 40: 2 infectious, 1 CNS bleed, and 1 sudden death. Based on intent to treat, 17 pts (53%) achieved complete remission, with or without full platelet recovery (15 CR, 2 CRp) after one cycle of induction. Following ATGO induction, 12 of the 17 responders went on to receive post-remission therapy consisting of allogeneic hematopoietic cell transplantation (HCT) for 8 pts (7 using reduced intensity conditioning), or standard consolidation alone (3 pts). Post-remission therapies, including HCT, were not associated with VOD/SOS or peculiar toxicities. As expected, achievement of CR after ATGO was associated with improved overall survival (p=0.043). Estimated 2 year OS for all pts is 34% (49% for responders vs. 14% for non responders). There was a trend toward improved survival in younger pts. Cytogenetic class, type of disease (MDS v. AML), and administration of prior chemotherapy were not significant predictors of either CR or OS. 15 pts (47%) are alive, with a median follow-up of 242 days (37–1182); 7 are currently in CR, including 5 of the 8 pts who received allogeneic HCT. Conclusions: Our data show that ATGO is well tolerated and without associated VOD after a single delivered dose of GO. The pathophysiology of the reversible delirium in the highest GO dose cohort remains unclear, but no neurologic effects were observed at the lower dose levels. The CR rate is promising, as is the ability to deliver post-remission therapy including HCT, in this challenging patient population.

Description: Ruxolitinib (RUX) is an oral selective Janus-associated kinase 1 (JAK1) and JAK2 inhibitor that is approved by the FDA for the treatment of patients with myeloproliferative neoplasms. JAKs transmit the signaling of ligand binding to inflammatory cytokine receptors into intracellular responses, and inhibition of JAK is effective in the treatment of autoimmune disorders. In MHC-mismatched mouse transplant models, pharmacologic inhibition of IFNγR signaling with RUX reduced graft-versus-host disease (GVHD) and improved survival (Choi et al Blood 2012); and preliminary reports have shown that 13/14 patients with steroid-refractory acute (10) and chronic (4) GVHD responded to RUX therapy. (Sporell et al Blood 2014). Between 09/2014 and 7/2015, 16 patients (12M/4F), with hematological malignancies and recipients of unrelated donor (14), matched sibling (2) blood (15) or marrow (1) transplant developed quiescent (12) or de novo (4) severe (NIH criteria) steroid-dependent cGVHD and received RUX as 2nd (4), 3d (7) 4th (4) or 5th (1) line salvage. 12 had prior grades 1 (3) 2 (6) 3(2) or 4 (1) acute GVHD that affected the skin (12) and gastrointestinal system (GI, 5). Median time of onset of cGVHD was d+130 (range, 90-299), and affected skin (16) eyes (12), mouth (10), GI (8), lungs (4), liver (3) and the musculoskeletal system (3). cGVHD was steroid dependent with recurrences of cGVHD symptoms with steroid tapers that were attempted a median of 4 times(range, 2-10). Median duration of continuous exposure to steroids for cGVHD was 24 months (range, 6-53). RUX was administered at the dose of 5 mg BID. Median weight was 82 kg (range, 56-158). RUX dose was increased to 15 mg/d (4) or 20 mg/d (3) due to physician preference (4), patient weight (1), or flare of cGVHD after initial response due to discontinuation of immunosuppression (1) or temporary perioperative hold of RUX (1). Median duration of RUX therapy was 6 months (range 1-14). All patients were evaluable for response. Complete resolution of clinical manifestations of cGVHD was observed in the following organs: lungs (dyspnea/O2 dependence), mouth (oral ulcerations), skin (non-sclerodermatous erythema), liver (sGOT, sGPT, alkaline phosphatase), musculoskeletal and GI (dysphagia, diarrhea). Subjective improvement was reported in sclerodermatous and ocular cGVHD. Responses were observed early after initiation of RUX (median 14 days). Prednisone was successfully reduced to physiologic doses (n=2) or discontinued (n=10) in 12 (75%), and taper is currently in progress for the 4 patients who started RUX in the past 8 weeks. Median time from initiation of RUX to prednisone discontinuation was 72 days (range, 31-120). With a median follow-up of 4 months (range, 1-12) from prednisone discontinuation/reduction to physiologic doses, 2 patients experienced a transient flare of cGVHD symptoms associated with discontinuation of immunosuppression (1) and temporary hold of RUX. None of the other patients required a restart of prednisone or increased immunosuppression. We conclude that RUX is an effective steroid-sparing agent in steroid-dependent severe cGVHD. Validation of these results in prospective trials is needed. Disclosures Jillella: Seattle Genetics, Inc.: Research Funding.