ALBERT

Description: Key Points Donor-derived Tc17 cells differentiate early after allogeneic transplant in response to IL-6 and alloantigen presentation by host DCs. Tc17 are highly proinflammatory and pathogenic posttransplant, but exert limited or no GVL activity.

Description: Introduction: Aggressive chemo-immunotherapy followed by peripheral blood stem cell autografting (ASCT) in CALGB 59909 achieved a median progression-free survival (PFS) in MCL of 5 years (Damon et al JCO, 2009), but late recurrences occurred. Bortezomib has a 33% response rate in relapsed/refractory MCL. Using the CALGB 59909 treatment backbone, we evaluated tolerability and efÞcacy of adding post-transplant BC or BM in a randomized phase II trial. Methods: The primary endpoint was PFS estimated from study entry for each treatment arm. Induction therapy was with 2-3 cycles of augmented R-CHOP (2000 mg/m2 cyclophosphamide) and methotrexate (300 mg/m2) followed by high-dose cytarabine/etoposide/rituximab(R)/Þlgrastim (EAR) stem cell mobilization and cyclophosphamide/carmustine/etoposide (CBV) ASCT. After 2 doses of post-transplant R, patients were randomized to BC (1.3 mg/ m2 days 1, 4, 8, 11 of a 3 week cycle for 4 cycles) or BM (1.6 mg/m2 weekly 4 of 8 weeks for 18 months) beginning at approximately day 90. Minimal residual disease (MRD) was analyzed using patient-specific PCR probes for the bcl-1 / IgH junction or the IgH CDR3 region. Results: 151 patients were enrolled at 14 sites and 147 received treatment. Median age was 59 (29-69); stage II (2.7%), III (12%), IV (86%); MIPI low (52.4%), int. (30.6%), high (17%); blastoid histology (14%); bone marrow involvement (81%). 118 (88%) underwent ASCT and 102 (68%) were randomized. Most withdrawals (45) were for progression (10) or adverse events (AEs) (19) including 4 treatment-related deaths. Following randomization, 34 (65%) completed BM and 33 (66%) completed BC. Withdrawal for AEs occurred in 14 (28%) of BC and 7 (13%) of BM patients (p = 0.088), most for cytopenias or peripheral neuropathy. Median follow-up was 5.5 years from registration. Median PFS was significantly greater than the null hypothesis (4 years) for both BM and BC (1-sided test of exponential parameter p 〈 0.001). The 5-year PFS estimates from study entry in the BM and BC arms were 70% (55-81%) and 69% (54-80%), respectively. Progression occurred in 17 BM (12 post-treatment) and 19 BC patients (all post-treatment). Five-year PFS from time of transplantation in CALGB studies 50403 (n=118) and 59909 (n=66) was 72.7% (63-80%) and 51.5% (36.7-62%), respectively (log rank p=0 0006) favoring the 50403 trial which differed from 59909 only by the addition of post-transplant bortezomib. MRD results were available in 47 patients. Five-year PFS from study entry was 93% if MRD-negative (n=15) and 51% if MRD-positive (n=32) following induction chemo-immunotherapy (log rank p=.003) (See figure). Conclusions: Induction chemotherapy followed by ASCT and either BC or BM was efficacious and tolerable, although BC was associated with more withdrawals for toxicity. The comparison between studies 50403 and 59909 suggests a PFS benefit from the addition of BC or BM. MRD-negativity following induction chemo-immunotherapy is highly associated with improved PFS and could provide an important tool for designing future trials. Figure 1. Figure 1. Disclosures Off Label Use: Post-autotransplant use of bortezomib . Bartlett:Seattle Genetics: Consultancy, Research Funding; Gilead: Consultancy; Janssen: Research Funding; Pharmacyclics: Research Funding; Astra Zeneca: Research Funding; ImaginAB: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Medimmune: Research Funding; Millenium: Research Funding; Celgene: Research Funding. Byrd:Acerta Pharma BV: Research Funding. Blum:cephalon: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding. Hurd:Procter and Gamble: Equity Ownership; Medtronic: Equity Ownership; Pfizer: Equity Ownership; Merck: Equity Ownership; Bristol Myers Squib: Equity Ownership. Czuczman:MorphoSys: Consultancy; Cellgene: Employment; Immunogen: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees. Leonard:Weill Cornell Medical College: Employment; Genentech: Consultancy; Medimmune: Consultancy; AstraZeneca: Consultancy; Spectrum: Consultancy; Boehringer Ingelheim: Consultancy; Vertex: Consultancy; ProNAI: Consultancy; Biotest: Consultancy; Seattle Genetics: Consultancy; Pfizer: Consultancy; Mirati Therapeutics: Consultancy; Gilead: Consultancy; Novartis: Consultancy. Cheson:AstraZeneca: Consultancy; Astellas: Consultancy; Ascenta: Research Funding; Spectrum: Consultancy; Teva: Research Funding; MedImmune: Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Description: Background: Therapy for patients (pts) with high risk AML remains unsatisfactory. Retrospective studies have demonstrated activity of fludarabine, cytarabine, GCSF and idarubicin (FLAG-IDA) and of mitoxantrone, etoposide and cytarabine (NOVE-HiDAC) as salvage therapy in pts with relapsed or refractory AML. A recent randomized trial indicated high complete remission (CR) rates with improved relapsed-free survival when FLAG-IDA is administered as frontline induction therapy (Burnett et al. J Clin Oncol 2013). Since 01/2011, we have used FLAG-IDA as a first line therapeutic option in pts with high risk AML (poor risk cytogenetics, antecedent myeloproliferative neoplasm or myelodysplastic syndrome, and/or therapy-related AML) in an attempt to improve CR rates and permit more patients with AML to advance to allogeneic hematopoietic cell transplantation (alloHCT). Prior to 2011, either 3&7 or NOVE-HiDAC was used as first line therapy in patients with AML. Methods: We conducted a retrospective review of consecutive patients with high risk AML treated with front-line (a) FLAG-IDA between 01/2011 to 03/2015, (b) NOVE-HiDAC from 01/2006 to 12/2014, or (c) 3&7 from January 01/2011 to 12/2014 at the Princess Margaret Cancer Centre, to determine the CR rates and overall survival (OS) associated with the different regimens. Results: Patients characteristics are in Table 1. Fifty-two, 32, and 30 pts received FLAG-IDA, NOVE-HiDAC or 3&7 as first induction, respectively. Patients receiving FLAG-IDA had more high-risk features (i.e. complex cytogenetics, more azacytidine failures) compared to those receiving 3&7. Overall CR rate (i.e. CR + [CRi] + [CRp]) with FLAG-IDA, NOVE-HiDAC, and 3&7 respectively was 86% (n=42/49), 84% (n=21/25) and 50% (n=13/26), respectively. Median CR duration, censored at time of transplant, for pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 was 3 mos (0.5-15), 3.5 mos (1-9) and 5.5 mos (0.5-42), respectively. OS at 1 year with FLAG-IDA, NOVE-HiDAC and 3&7 was 61% (95% CI, 41% -75%), 55% (95% CI, 34%-72%) and 21.6% (95% CI, 7.4%-40.7%), respectively (log-rank test p-value=0.0076). On subgroup analysis, there was no statistical difference in OS for pts ≥70 years. Of those with a donor identified, 35% (n=13/37), 73% (n=11/15) and 29% (n=5/17) of pts who were treated with FLAG-IDA, NOVE-HiDAC and 3&7 underwent an alloSCT, respectively. Pts with sAML may have had a higher transplant rate due to donor searches initiated earlier. Probable and possible invasive aspergillosis infections in pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 were 50%, 34% and 33% respectively. Institution of earlier bronchoscopies led to increased fungal detection in the FLAG-IDA group. Median length of stay and ICU transfers were similar between groups. Induction deaths were secondary to sepsis, respiratory failure, invasive aspergillosis, and hemorrhage; these were similar across groups. Two pts receiving NOVE-HiDAC, with prior MPN, died of progressive splenomegaly and liver failure. Conclusions: Toxicities associated with frontline FLAG-IDA and NOVE-HIDAC induction are acceptable. FLAG-IDA and NOVE-HiDAC induction can result in durable CR, permitting patients with high risk AML to proceed to alloSCT and providing more favourable survival rates than frontline 3&7. Randomized studies are needed to confirm these findings for pts with poor-risk sAML and tAML. Table 1. Patient Characteristics FLAG-IDA(2013-2015) NOVE-HiDAC(2006-2014) 3&7(2011-2014) N=52 N=32 N=30 Median Age,y (range) Age

Description: Key Points Germline gain-of-function mutations in STAT3 lead to lymphoproliferation and autoimmunity with prominent cytopenias. Mutations in STAT3 cause altered regulatory T cells and cytokine signaling.

Description: Introduction We previously reported on the generation of highly activated/expanded natural killer cells (ENKs) after coculture with K562 cells modified to express membrane bound IL15 and 41BB-ligand. These cells have potent antimyeloma properties in vitro, in a NGS mouse model, and are safe when given to advanced multiple myeloma (MM) patients. (Szmania et al, J Immunother 2015) A potential obstacle to the effectiveness of ENK-based immunotherapy of MM is the evasion of immune recognition. We have generated 4 MM cell lines (OPM2, JJN3, ANBL6, and INA-6) which are resistant to ENK-mediated lysis to study mechanisms of resistance. These lines were derived from parental lines by repeated challenge with ENKs and maintained resistance long term when cultured without further exposure to ENKs.(Garg et al, Blood 2012, 120:4020) We have shown by stable isotope labeling with amino acids in cell culture-mass spectrometry, gene expression profiling (GEP), and flow cytometry that ICAM3 is downregulated in the ENK-resistant version of OPM2 (OPM2-R) compared to the parental OPM2. (OPM2-P; Garg et al, Blood 2013, 122:3105) We investigated OPM2-P and OPM2-R by whole exome sequencing (WES) and RNA sequencing (RNAseq) with a focus on ICAM3, evaluated ICAM3 cell surface expression on patient myeloma cells, and studied the importance of ICAM3 expression on ENK functionality. Methods DNA and RNA were extracted from OPM2-P and OPM2-R cells using the Qiagen AllPrep kit. WES libraries were prepared with the Agilent qXT and Agilent SureSelect Clinical Research Exome kits with additional baits covering the Ig and MYC loci. RNAseq libraries were prepared using the Illumina TruSeq stranded mRNA kit. Samples were sequenced 100bp PE on an Illumina HiSeq2500. Samples for WES were sequenced to a mean coverage of 〉120x and RNAseq to a target of 〉100M reads. WES data were aligned to the Ensembl GRCh37/hg19 human reference using BWA mem. Somatic variants were called MuTect. RNAseq data were analyzed using Tuxedo Suite. Data were aligned to the Ensembl GRCh37/hg19 human reference using TopHat with Bowtie2. Transcriptome reconstruction, quantification and differential analysis was performed using CuffLinks. ENK-mediated lysis of myeloma cells was measured by 4 hour chromium release assay in the presence of isotype or ICAM3 blocking antibody. Bone marrow aspirates were obtained from MM patients after informed consent in accordance with the Declaration of Helsinki. Primary myeloma cells were selected with CD138-coated immunomagnetic beads and ICAM3 expression was assessed by flow cytometry gated on viable CD138 positive cells. Results There was no mutation in ICAM3 in OPM2-R by WES, but RNAseq found a significant reduction in ICAM3 RNA in OPM2-R compared to OPM2-P (p

Description: Background: Primary testicular diffuse large B cell lymphoma (DLBCL) is an uncommon malignancy portending a poor prognosis with increased risk of central nervous system disease. Phenotypically, most primary testicular lymphomas have a non-germinal center B-cell like (non-GCB) origin. To identify the genetic characteristics of testicular DLBCL, we evaluated DNA copy number and mutational profiling using SNP array and a next generation targeted sequencing platform. Methods: Twelve cases of testicular DLBCL with patient consent for tissue specimens and sufficient tumor tissue were retrospectively identified. Cell of origin was determined by Hans immunohistochemistry (IHC) model. We performed a custom, targeted deep-sequencing assay of 585 cancer genes (HemePACT) on matched tumor and normal pairs. Barcoded pools were sequenced on Illumina HiSeq 2500 to 500-1000x coverage per sample Sequencing was compared to a matched normal tissue control (N=10) if available or alternatively a pooled normal tissue control. We excluded all mutations either present at a high variant allele frequency in the matching germline samples, present in two databases of inherited variants (DBSNP and 1000 genomes) or present in one databases of inherited variants and absent from COSMIC. We evaluated copy number and allelic imbalance with an Affymetrix OncoScan SNP-array. IHC was performed for select genes. Results were compared to a panel of non-testicular DLBCL previously described (N=78). Results: The median age of the patients was 55.1 years (range 21.9-77.9). Patients had clinical stage IE (50%) and IV (50%) disease. All samples were sequenced from pre-treatment biopsies. Eleven of 12 patients were initially treated with R-CHOP chemotherapy, intrathecal methotrexate and radiation. Treatment history for one patient was unknown. We identified 124 mutations in 12 cases of testicular DLBCL. The most common mutation was MYD88 occurring in 10/12 patients (83%) with 6 mutations in non-GCB and 2 mutations in GCB (Fig 1A). The MYD88 L265P allele was most frequent and occurred in 9/12 patients (75%). The median MYD88 L265P variant allele frequency was 0.36 (range 0.07-0.51) with normal copy number status at that loci. In contrast, MYD88 mutations were less frequent in DLBCL without testicular involvement, 12/37 (32%) non-GCB and 3/41 (7%) GCB DLBCL, p

Description: Introduction: Acute leukemias of ambiguous lineage (AUL), biphenotypic leukemias (BAL) and mixed phenotypic leukemias (MPAL) are a heterogeneous group of rare, poorly characterized leukemias with unfavorable outcomes. AUL, BAL and MPALs are believed to constitute 2-5% of all leukemias. The optimal treatment regime for this group of leukemias is currently unknown. The primary objective of this study is to determine the complete remission rate (CR) and overall survival (OS) among adult patients with mixed phenotypic leukemia, not otherwise specified (NOS), as defined by the WHO 2008 classification criteria. Methods: Patients with mixed phenotype acute leukemia (MPAL) older than 17 years of age who were treated at Princess Margaret Cancer Centre from January 1, 2000 to June 30, 2014 were identified through the Leukemia Database at Princess Margaret Cancer Registry. Pathology review of the original diagnostic bone marrow was completed to ensure patients met the WHO 2008 criteria for MPAL, not otherwise specified (NOS). Patients with MLL+, BCR-ABL+, PDGRFA+ were excluded from analysis. Results: Fourteen patients were identified and confirmed by pathology review. Eleven (79%) were male, 3 (29%) were female. The median age was 57 years (range: 18-84). Eight (57%) had extramedullary involvement at presentation. Six (42%) had poor risk cytogenetics, whereas 8 (57%) had intermediate risk cytogenetics at presentation as per the MRC criteria. Two patients (14%) had p53 mutations/loss of chromosome 17. Four patients (42%) had monosomy 7 karyotype. Six cases (43%) were myeloid/B, seven cases (50%) were myeloid/T and one (7%) was myeloid/T/B type. The median WBC at presentation was 10.8 x 109/L (2.3 x 109/L-106 x 109/L). Five patients were treated upfront with daunorubicin and cytarabine (3&7) with 1 of these patients achieved a CR with this upfront regime. Five patients were treated upfront with the Dana Farber Consortium Protocol (DFCI) and 4 of these patients achieved a CR with this upfront regime. Two patients were treated upfront with HyperCVAD, and 1 achieved a CR. Two patients were treated palliatively. One received azacytidine as palliative treatment and achieved a CR with a duration of 5 months. Ten (71%) of these patients achieved a CR. Three of the primary nonresponders achieved a CR with an alternative induction regime. The median CR1 duration was 5.5 mos (range, 2-40 mos). Overall median survival was 13 mos (95% CI, 8 mos-27 mos). The OS at 1 year and 2 years was 56% (95% CI, 29%- 82%) and 32% (95% CI, 6%-57%), respectively. Four patients (29%) underwent an allogeneic hematopoietic stem cell transplant. At last follow up, 13 of the 14 patients have died, 11 from relapsed leukemia and 2 from sepsis post HCT. One patient died of relapsed leukemia post HCT. Conclusions: This retrospective review confirms the high risk nature and poor prognosis of MPAL NOS. Our limited cohort showed a male predominance, a high rate of extramedullary involvement at presentation, and a higher rate of CR with DFCI as the initial remission induction regime. HCT or other forms of maintenance therapy should be considered in CR1 in eligible patients due to the high- risk nature of MPAL NOS. Disclosures Gupta: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

Description: Background: Children and adults with Down Syndrome (DS) have an approximately 20-fold increased risk of developing acute lymphoblastic leukemia, which in the majority of cases is of the B-cell precursor (BCP) type, and have significantly inferior outcomes due to both higher relapse rates and increased treatment-related mortality.During treatment for ALL, children with DS are at a higher risk of complications such as prolonged neutropenia, severe mucositis and longer hospitalizations. In view of the significant barriers to successful treatment for pediatric DS-ALL and the absence of outcome data for DS-ALL in adults, we retrospectively reviewed the outcomes of adult patients with DS-ALL treated at our center. Methods: All patients greater than 18 years of age diagnosed with DS-ALL who were followed at Princess Margaret Cancer Center/University Health Network (PMH/UHN) between January 1, 2000 and June 30, 2014 were identified using the institutional leukemia database. Diagnosis of ALL was established by standard FAB WHO Criteria using multiparameter flow cytometry for immunophenotyping according to ISCN guidelines. Treatment of adult DS patients with de novo ALL and those with relapsed ALL who had not previously received intensive asaparaginas therapy, were treated according to a modified Dana Farber Cancer Institute (DFCI) ALL regimen; reduced doses of methotrexate were used due to the increased risk of mucositis reported in children with DS. This regimen includes an at least four fold higher total dose of E. coli derived asparaginase compared to other adult regimens. Results: Seven adult patients with DS-ALL were treated at our center from 2000 to 2014. Four of these were diagnosed with de novo DS-ALL (after age of 18 years) and three patients developed a late isolated bone marrow relapse of DS-ALL as adults after previous treatment for childhood DS-ALL. Approximately half of our patients had favourable cytogenetics and half had intermediate risk cytogenetics . Treatment was not altered based on cytogenetics. The median age of 4 patients, with de novo adult DS-ALL, was 26 years (range 21-42 years). 75% achieved a CR after initial induction; one patient died during induction from sepsis. Two of the four de novo adult DS-ALL patients relapsed after CR1 durations of 11 and 35 mon.. One patient received palliative chemotherapy. At the time of last follow up, 3 of these patients have died. The one remaining patient is alive in continuous CR at 41 mos. The three adult DS patients with relapsed ALL had a median age of 14 years (7-15 years) at diagnosis of primary DS-ALL and 29 years (21-36) at the diagnosis of relapse. Two of these received DFCI as re-induction while the third received Hyper-CVAD. Despite achieving an initial remission all patients with relapsed DS-ALL died , two from subsequent relapsed and one from an invasive aspergillosis. One patient relapsed while on therapy at 4.7 months. The other patient relapsed while off therapy at 15.2 months. The overall and relapsed-free survival of adult patients with DS and de novo ALL at 3 years was 50% and 33.3%, respectively, and thus markedly inferior to results of a similarly treated population of adults (aged 18-35 years) without DS ( 3-year OS 83%, 3-year RFS 77%) at our center. Conclusions: The results of our series of adult patients with DS and ALL suggest that the barriers to successful treatment of ALL in adults with DS are similar to those observed in children. Although the rarity of adult ALL in general, and that of adult DS-ALL in particular, limits sample size and conclusions, this report is to our knowledge the first describing survival outcomes of adults with DS and ALL and highlights that treatment of primary adult DS-ALL is feasible but significantly less successful compared to adults without DS. As in children, subsequent relapse and treatment-related mortality impacting outcome are equally problematic. Disclosures Gupta: Incyte: Honoraria, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Ibrutinib has shown remarkable safety and efficacy in CLL. Due to CYP3A4 (3A4) metabolism, the concurrent use of 3A4 inhibitors/inducers with ibrutinib should be avoided. Ibrutinib is also associated with bleeding complications, in part due to effects on collagen-mediated platelet aggregation, thus caution is advised with the simultaneous use of anticoagulant (AC) and antiplatelet agents. It is unknown what proportion of CLL patients starting ibrutinib therapy in routine practice are on these medications. We conducted a retrospective study to evaluate these aspects in a large cohort of CLL pts treated with ibrutinib outside the context of clinical trials. Methods: Following IRB approval, consecutive CLL pts who initiated ibrutinib off-protocol at Mayo Clinic, Rochester, MN from November 2013 through July 2015 were evaluated. A medication review for drug-drug interactions was performed by a pharmacist on all pts. Baseline characteristics, concomitant medications, and toxicity were recorded. Time to toxicity and ibrutinib discontinuation were analyzed by Kaplan Meier and cumulative incidence methods accounting for competing risk of death, respectively. Results: Ninety-six CLL pts started ibrutinib. Median age was 66 years and 64 (67%) were male. Ibrutinib indications included: relapsed/refractory CLL (n=84), treatment-naïve CLL with del17p (n=8), and CLL with Richter's transformation (n=4). Approximately 80% had unmutated IGHV and 45% had del17p or del11q on FISH. Upon initial pharmacy consult prior to ibrutinib, the median number of concomitant medications was 9 (range, 1-31). Sixty (63%) pts were taking concurrent medications increasing their risk of ibrutinib toxicity and 4 (4%) pts were on drugs potentially reducing ibrutinib efficacy. At ibrutinib initiation, 16 (17%) pts were on concomitant 3A4 inhibitors. This included 9 (9%) on moderate 3A4 inhibitors (fluconazole, diltiazem, imatinib, cyclosporine) and 7 (7%) on strong 3A4 inhibitors (voriconazole, posaconazole, clarithromycin, itraconazole). In 4 pts, the 3A4 inhibitor was switched to another agent or discontinued to allow standard 420 mg daily dosing. Ibrutinib was initiated at 140 mg daily in 7 pts on moderate 3A4 inhibitors and at 140 mg every 48 hours in 5 pts on strong 3A4 inhibitors. Four (4%) pts were on strong 3A4 inducers (carbamazepine, rifampin, rifabutin) at the initiation of ibrutinib. The 3A4 inducer was discontinued prior to ibrutinib start in 3 pts, while the initial ibrutinib dose was decreased to 140 mg every 48 hours in the remaining patient (also on 2 strong 3A4 inhibitors). During the course of ibrutinib, an additional 8 (8%) pts were started on 3A4 inhibitors/inducers which necessitated dose modifications. Upon commencing ibrutinib, 9 (9%) pts were on concomitant AC (6 warfarin, 3 enoxaparin). Due to significant bleeding risk, warfarin was switched to enoxaparin in 2 pts, to aspirin (ASA) in 1 and warfarin was discontinued in 1. In 2 pts, an alternative AC could not be used so ibrutinib was begun at 140 mg daily and titrated upward. Twenty-nine (30%) pts were on ASA (3 [3%] also on clopidogrel) at ibrutinib initiation. Nineteen (20%) pts were on selective serotonin release inhibitors (SSRIs), and 9 (9%) were on NSAIDs. Thirteen (13%) pts were on fish oil and 24 (25%) were on herbal medications; all of which were discontinued prior to starting ibrutinib. Ten (10%) pts had clinically significant bleeding on ibrutinib including 4 (4%) requiring hospitalization (1 subdural hematoma). Of these 4 pts, 1 was on enoxaparin, 2 were on a SSRI and 1 a NSAID. Six pts had minor bleeding necessitating a dose reduction of ibrutinib to 140-280 mg daily. After 16 months follow-up, the risk of bleeding was 21% (95% CI: 1-37%, Figure). After a median follow-up of 7.6 months, 73 (76%) pts remain on ibrutinib. There was no difference in rates of discontinuation of ibrutinib between patients who were on 3A4 inhibitors/inducers versus those who were not. Conclusion: In the "real-world" setting, 2 out of 3 CLL patients commencing ibrutinib therapy is on a concomitant medication with a potentially clinically significant drug-drug interaction with ibrutinib. These findings have implications for the practicing hematologist who must maintain a high degree of vigilance when prescribing ibrutinib to CLL pts. We highly recommend a formal medication review by a clinical pharmacist in all patients initiating ibrutinib. Figure 1. Figure 1. Disclosures Ding: Merck: Research Funding. Kay:Hospira: Research Funding; Tolero Pharma: Research Funding; Genentech: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shanafelt:Glaxo-Smith_Kline: Research Funding; Pharmactckucs: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Cephalon: Research Funding; Janssen: Research Funding; Hospira: Research Funding; Polyphenon E Int'l: Research Funding.

Description: Key Points IL-6 is dysregulated after experimental allogeneic SCT and promotes alloantigen-dependent Th17 expansion within the lung. IL-6 is dysregulated in patients with IPS after clinical allogeneic SCT.