Search

Relapse after allogeneic stem cell transplant in unfavorable-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) portends a poor prognosis. We conducted a single-center phase I dose-escalation study with lenalidomide maintenance in high-risk MDS and AML patients after allogeneic transplantation. Sixteen patients enrolled in a “3 + 3” study design starting at lenalidomide 5 mg daily, increasing in increments of 5 mg up to 15 mg. Lenalidomide was given for 21 days of a 28-day cycle for a total of six cycles. Most common dose-limiting toxicities were lymphopenia, diarrhea, nausea, and neutropenia. Two patients had acute graft-versus-host disease (GVHD), and five patients developed chronic GVHD. The maximum tolerated dose was 10 mg, after dose-limiting toxicities were seen in the 15 mg group. Two dose-limiting toxicities were seen from development of acute GVHD and grade III diarrhea. Limitations of the study include time to initiation at 6 months post transplant, as many high-risk patients will have relapsed within this time frame before starting maintenance lenalidomide. Overall, lenalidomide was well tolerated with minimal GVHD and low rates of relapse rates, warranting further study.

Background FLAG ± Ida (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), is a salvage chemotherapy regimen for relapsed or refractory (R/R) acute myeloid leukemia (AML), with complete remission (CR) rates historically ranging from 52% to 63%. We review the outcomes for patients with R/R AML treated with FLAG ± Ida at the University of California Davis Comprehensive Cancer Center. Patients and Methods Adult patients (≥ 18 years) with R/R AML who received FLAG or FLAG + Ida from January 1, 2012 to October 31, 2016 were identified via chart review. Outcomes evaluated were CR, CR with incomplete hematologic recovery (CRi), overall response rate, overall survival (OS), relapse-free survival, and adverse events. Results Forty-two patients were included. The median age was 52 years (range, 23-73 years), and 57% were male. Sixteen (38.1%) patients had relapsed disease, and 26 (61.9%) had refractory disease. Most (n = 35; 83.3%) patients had European LeukemiaNet intermediate-risk AML. Responses were CR in 20 (47.6%) and CRi in 6 (14.3%). The median OS was 10 months (range, 0.8-51 months), and the median relapse-free survival was 12 months (range, 1-51 months) for responders. The median OS for patients who achieved CR was not reached, and the estimated 48-month survival rate was 56%. The median OS after CRi or no response was 3.47 and 2.17 months, respectively. The median OS was not significantly different when censored for stem cell transplant following chemotherapy, nor with use/deferral of idarubicin. The most common adverse effects were pancytopenia and infection. Conclusion Patient outcomes after treatment with FLAG ± Ida for R/R AML remain similar to prior reports, confirming its role as a salvage regimen for these patients.

Introduction Everolimus and bendamustine both have single-agent activity against lymphoid hematologic malignancies. We examined this combination in a group of heavily pretreated patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM). Patients and Methods In this phase I trial, 18 patients (8 with NHL, 6 with MM, and 4 with HL) were treated with bendamustine 90 mg/m2 on days 1 and 2 and everolimus from 5 to 10 mg daily on a 28-day cycle, for up to 4 cycles. Results Adverse events were generally mild and mostly hematologic in nature. The most frequent grade 3/4 adverse events were lymphopenia (61%), thrombocytopenia (22%), leukopenia (22%), neutropenia (17%), and fatigue (17%). Overall response rate varied by malignancy: diffuse large B-cell lymphoma, 20% (1 of 5 patients); HL (2 of 4 patients), 50%; MM, 80% (4 of 5 patients); and indolent lymphomas, 100% (3 of 3 patients). The maximum tolerated dose of everolimus was determined to be 7.5 mg daily. Conclusion The combination of everolimus and bendamustine appeared to be well-tolerated and relatively efficacious.

Allogeneic hematopoietic cell transplantation (alloHCT) can produce durable remissions in refractory lymphomas by relying on both myeloablative conditioning (MAC) and the subsequent graft-versus-ly...

Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated. We sought to validate those findings in previously untreated adult patients with Ph+ ALL.This was a retrospective study analyzing the outcomes of previously untreated adult ALL patients treated with hyper-CVAD, with a focus on Ph+ ALL patients treated with ponatinib plus hyper-CVAD.82 patients were included. The median age was 51 years. The median follow-up was 2.62 years. The 5-year overall survival (OS) and event-free survival (EFS) were 39.5 % and 28.2 %, respectively. For Ph+ ALL patients (n = 13) receiving ponatinib plus hyper-CVAD, 3-year OS and EFS were both 92.3 %. Univariate analysis showed a high WBC and poor-risk cytogenetics to be associated with inferior outcomes, while CD20 + predicted favorable outcomes in B-ALL patients. On multivariate analysis, CD20 + retained significance for Philadelphia-negative (Ph-) ALL. For Ph+ ALL, ponatinib was associated with better OS and EFS on univariate and multivariate analysis.Our data supports the use of ponatinib plus hyper-CVAD as a standard of care regimen for Ph+ ALL. Our outcomes for Ph-ALL and T-cell ALL (T-ALL) show that advances are still needed in the frontline setting, and clinical trial enrollment is recommended.

Autologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated using the Fine and Gray method. Among 16,331 patients, 933 (5.7%) developed a SPM more than 1 year after diagnosis. The 10-year CMI of developing any SPM was 6.6%, 5.7% for solid tumor SPM and 0.9% for hematologic malignancies. The 10-year CMI of developing any SPM was similar among aHSCT [9.1% (7.7–10.7%)] and non-aHSCT [7.5% (6.5–8.6%)] (P = 0.26) recipients and there was no difference in solid-tumor SPMs (P = 0.98). The 10-year CMI of hematologic SPMs was higher among aHSCT recipients [2.1% (1.4–2.9%) vs. 0.8% (0.5–1.2%); P = 0.005], corresponding to a 1.3% absolute increase and an aHR of 1.51 (1.01–2.27). Ten-year myeloma-specific and non-cancer mortality rates were 59% (58.2–60.0%) and 18.1% (17.4–18.8%), respectively. Although aHSCT was associated with a small increase in hematologic SPMs, mortality was driven by MM and non-cancer causes.

Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using venetoclax in combination with decitabine or azacitidine, which is not otherwise widely evaluated in the current literature. Our patients come from a large, socioeconomically and geographically diverse area including the majority of Northern California. Most had ELN Adverse Risk (52%) or Intermediate Risk (44%) AML, and most had an ECOG Performance Status of 1 (64%). Over half (52%) had prior hypomethylating agent exposure, and 40% had Secondary AML. We observed an overall response rate of 52%, with eight patients (32%) achieving composite complete remission. Median overall survival was 5.5 months, and for patients achieving composite complete remission this was 21.6 months. One-year estimated overall survival was 38%. Three patients were able to proceed directly to stem cell transplant for consolidation, and all three were alive at last follow-up, ranging 13.8–24.0 months. We found venetoclax in combination with hypomethylating agents to be well tolerated and potentially efficacious in securing long-term remissions for patients with relapsed/refractory AML.

Background Ponatinib, a third-generation BCR-ABL1 tyrosine kinase inhibitor (TKI), + hyper-CVAD showed remarkable activity against Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and may be superior to chemotherapy + earlier generation TKIs in terms of depth of remission, event-free survival (EFS), and overall survival (OS). However, this regimen's efficacy and tolerability have yet to be externally validated. Here, we summarize our real-world experience with ponatinib + hyper-CVAD for untreated Ph+ ALL and other Ph+ acute or blast phase leukemias. Methods We retrospectively analyzed all adults treated at the University of California, Davis (UCD) from March 2012 to May 2021 with ponatinib + hyper-CVAD upfront. The primary endpoints were 3-year OS and EFS. Secondary endpoints were complete molecular response (CMR), measurable residual disease (MRD) negativity by multiparameter flow cytometry (MFC), complete cytogenetic response (CCyR) rates, and adverse events (AEs). Time to event analyses were done via the Kaplan-Meier method. Patients alive were censored at their last follow-up date. Patients undergoing allogeneic hematopoietic cell transplant (HCT) after 6 months of achieving complete remission (CR) were censored at the time of HCT for the landmark analysis. Patients with missing data were excluded from the response analyses. Results We identified 13 Ph+ ALL patients who received ponatinib + hyper-CVAD for initial induction. The baseline characteristics for the Ph+ ALL patients are summarized in Table 1. The median follow-up was 16 months. The median number of hyper-CVAD cycles completed was 8 (range, 1-8) with ponatinib. Two patients proceeded to HCT in CR1, one at 3.5 months after starting induction, and due to difficulty controlling the patient's concurrent multiple myeloma prior to HCT and recovery from anti-neoplastic therapy, the second was delayed to 46 months after starting induction. The 3-year OS and EFS with ponatinib + hyper-CVAD were each 92% (95% confidence interval, 78.9-100) (Figure 1). Landmark analysis completed 6 months following CR showed a 3-year OS of 100% in patients treated with ponatinib + hyper-CVAD without HCT in first CR (CR1). The CMR, CCyR, and MRD-negativity by MFC rates with ponatinib were all 92.3% (12/13). The median time to CMR, CCyR, and MRD-negativity by MFC were 51 days, 22 days, and 53 days, respectively. Notable AEs with ponatinib include neutropenic fever (92%), bacterial infection (69%), transaminitis (38%), venous thromboembolism (31%), invasive fungal infection (15%), hemorrhage (15%), cerebrovascular accident (CVA) (15%), and tumor lysis syndrome (8%). One patient died during induction with ponatinib due to a bacterial infection. Two patients switched to a different TKI due to a CVA after 4 and 24 months. Only 2 patients did not complete 8 cycles of hyper-CVAD, due to death during induction (n=1) and proceeding to HCT after 3 cycles (n=1). As for similar Ph+ leukemias, 3 chronic myeloid leukemia with lymphoid blast crisis (CML-LBC), 1 CML with mixed phenotype blast crisis (CML-MPBC), and 1 with mixed phenotype acute leukemia (MPAL) were treated with ponatinib + hyper-CVAD. The MPAL patient achieved CMR within 55 days, while the CML-MPBC and 2 CML-LBC patients achieved CMR after HCT. The third CML-LBC patient is in CR with ongoing treatment. After median follow-up of 25 months, all 5 were alive, and only the MPAL patient relapsed 28 months after starting treatment and 1 year after HCT. Conclusion To our knowledge, this is the first report externally validating the efficacy and tolerability of ponatinib + hyper-CVAD for Ph+ ALL. We also show the feasibility of using this regimen in patients with Ph+ CML-LBC, CML-MPBC and MPAL. Despite the small sample size and retrospective nature, our study supports existing data demonstrating that this regimen challenges both the designation of Ph+ ALL as a high-risk disease and the trend to transplant in CR1. Our findings support that ponatinib + hyper-CVAD should be considered a standard of care for Ph+ ALL. Figure 1 Figure 1. Disclosures Kaesberg: Incyte: Speakers Bureau. Rosenberg: Takeda, Janssen: Speakers Bureau. Abedi: BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Speakers Bureau; Seattle Genetics: Speakers Bureau. Tuscano: Genentech, Pharamcyclics, Abbvie, BMS, Acrotech, Seattle Genetics, Takeda: Research Funding. Jonas: AbbVie, BMS, Genentech, GlycoMimetics, Jazz, Pfizer, Takeda, Treadwell: Consultancy; 47, AbbVie, Accelerated Medical Diagnostics, Amgen, AROG, Celgene, Daiichi Sankyo, F. Hoffmann-La Roche, Forma, Genentech/Roche, Gilead, GlycoMimetics, Hanmi, Immune-Onc, Incyte, Jazz, Loxo Oncology, Pfizer, Pharmacyclics, Sigma Tau, Treadwell: Research Funding; AbbVie: Other: Travel reimbursement. OffLabel Disclosure: Ponatinib is approved for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy. In this study, we described outcomes with ponatinib in combination with hyperCVAD in the frontline setting, which is off-label.

BACKGROUND GVHD and non-relapse mortality (NRM) remain frequent complications of HLA-matched HSCT despite the use of standard immunosuppression like tacrolimus and methotrexate. Alternative GVHD prophylaxis (PPX) strategies like T-cell depletion and post-transplant cyclophosphamide negatively impact relapse, infection, and organ toxicity, and no strategy has yet demonstrated a clear benefit for GVHD-free survival. Orca-T is an investigational cellular product comprising stem and immune cells that leverages highly purified donor regulatory T cells to control alloreactive immune responses. Unlike point-of-care graft engineering approaches, Orca-T is produced in a central GMP laboratory and has been successfully distributed to multiple centers across in the U.S. Early clinical trials using Orca-T showed a good safety profile, promising GVHD control, and potentially improved immune reconstitution. Here, we present trial results from both a single-institution Phase 1/2 trial that has completed enrollment and an ongoing multicenter Phase 1b trial. METHODS As of 28 July 2021, 113 patients aged 18-72 have received Orca-T for AML, ALL, MDS, lymphoma, or myelofibrosis. We present here data from 80 patients that have ≥90 days follow-up. 28 and 52 patients, respectively, received Orca-T followed by single-agent GVHD prophylaxis on a single-center Phase 2 study (NCT01660607) and a multicenter Phase Ib (NCT04013685). Orca-T products were derived from HLA-matched related (n=46) or unrelated (n=34) donors. Patients received a variety of myeloablative conditioning regimens (e.g., non-TBI, n=66; TBI-based, n=14) followed by single-agent PPX with either tacrolimus (n=73) or sirolimus (n=7). Median follow-up for these patients is 541 days (single-center) and 248 days (multicenter). We identified a contemporaneous SOC cohort, and we reported on their clinical outcomes at Stanford (n=95) with both matched related (n=52) and unrelated (n=43) transplant recipients who received unmanipulated PBSC products (median f/u 546) and methotrexate plus tacrolimus prophylaxis. RESULTS The Orca-T investigational cell therapy was manufactured reliably, delivered in less than 72 hours for all patients, and every patient enrolled received Orca-T. The Treg drug product was characterized by high Treg purity of 93.8% +/- 3.1% and a dose of 2.6 +/- 0.4 x 106 per kg (equivalent between trials). An Orca-T product was produced and infused for all patients, and there were no logistics failures or infusion reactions. All patients engrafted and Orca-T patients showed earlier neutrophil (median of 12 days vs. 14 days, p On the single-center, Phase 2 clinical trial study at Stanford there is evidence of improved 1-year GVHD and relapse-free survival (GRFS) which was 77% (CI 51-88%) for Orca-T patients vs 34% (CI 25-44%) with SOC (Figure 1A). We observed improved rates of >grade 2 acute GVHD at Day +180 (aGVHD, 14% versus 33%), moderate-to-severe chronic GVHD at 1 year (4% versus 42%) and NRM at 1 year (0% versus 13%). Relapse-free (RFS) and overall survival (OS) trended upwards for Orca-T. Severe infectious complications were rare. Key clinical results from both Orca-T trials are summarized in Table 1; 23 of 80 patients had ≥1 year follow-up. Consistent with findings from the single-institution study, on the multicenter study, rates of moderate-to-severe cGVHD and non-relapse mortality were low at 1-year post-transplant at 3% and 4%, respectively. For all patients who received Orca-T across both studies, we observed GRFS of 72% (Figure 1B), RFS of 78%, and OS of 91% at 1 year. These survival rates compare favorably to the contemporaneous SOC control (33%, 71% and 78%, respectively). Immune reconstitution in Orca-T patients with single agent tacrolimus appears similar to SOC except for observable differences in the IL-2 pathway. CONCLUSIONS Manufacture of high precision Orca-T investigational cell therapy drug products was scaled in a central GMP with reliable distribution to centers. Patients that received Orca-T and single-agent PPX showed significantly reduced aGVHD, cGVHD and NRM. Orca-T shows promise to improve GRFS and other transplant outcomes. Orca-T has been granted Regenerative Medicine Advanced Therapy status by the FDA, and a phase 3 prospectively, randomized study is planned. Figure 1 Figure 1. Disclosures Gandhi: Gamida Cell: Consultancy, Membership on an entity's Board of Directors or advisory committees; CareDx Inc: Honoraria. Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding. Shiraz: Kite Pharma-Gilead: Research Funding. Mehta: Kadmon: Research Funding; Incyte: Research Funding; CSLBehring: Research Funding; Syndax: Research Funding. McGuirk: Allovir: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Gamida Cell: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Bellicum Pharmaceuticals: Research Funding; Pluristem Therapeutics: Research Funding; Fresenius Biotech: Research Funding; Astelllas Pharma: Research Funding; Novartis: Research Funding. Waller: Verastem Oncology: Consultancy, Research Funding; Cambium Oncology: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Arai: Magenta Therapeutics: Research Funding. Rezvani: US Department of Justice: Consultancy; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding; Kaleido: Other: One-time scientific advisory board. Weng: Kite Pharma: Research Funding. Miklos: Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Pharmacyclics: Patents & Royalties. Frank: Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Research Funding; Allogene Therapeutics: Research Funding. Fernhoff: Orca Bio: Current Employment. Putnam: Orca Bio: Current Employment. McClellan: Orca Bio: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Abedi: Seattle Genetics: Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Speakers Bureau. Meyer: Triursus Therapeutics: Current holder of stock options in a privately-held company; GigaImmune: Current holder of stock options in a privately-held company; Orca Biosystems: Research Funding; Indee, Jura: Consultancy.

Background Relapsed/refractory (R/R) acute myeloid leukemia (AML) remains a challenge to cure. Prior studies of hypomethylating agent (HMA) decitabine (DEC), proteasome inhibitor bortezomib (BTZ), and anthracycline (AC) pegylated liposomal doxorubicin (PLD) monotherapy, as well as DEC + BTZ and BTZ + PLD regimens, have demonstrated safety and modest activity in R/R AML. Inhibition of NF-κB signaling by BTZ and DEC could prevent AC resistance resulting from NF-κB activity. Thus, we hypothesized that the DEC + BTZ + PLD (DBP) regimen would have activity in R/R AML. Methods We performed a phase II trial of DBP, with a safety lead-in cohort, in patients aged 18-90 with R/R AML. The original protocol called for 1-4 28-day (D) cycles of induction with intravenous (IV) DEC 20mg/m 2 on D1-10, subcutaneous (SQ) BTZ 1.3mg/m 2 on D1, 4, 8, and 11, and IV PLD 40mg/m 2 on D4. Dose-limiting toxicity (DLT) of grade 3 peripheral neuropathy (G3 PN) in the first 2 patients led to a revised schedule of BTZ on D5, 8, 12, and 15 and PLD on D12, eliminating simultaneous DBP dosing on any 1 day. Patients achieving a bone marrow blast count Results Ten patients were enrolled from May 2016 to February 2018, after which the sponsor closed the protocol. Median age was 57 years [range 27-69]. Patients were 50% female, 60% White, 10% African American/Black, 30% other/mixed race, and 40% Hispanic/Latino, with median baseline ECOG score of 1 [0-1] and median 2 [1-3] lines of prior therapy. Sixty percent had de novo and 40% had secondary disease. By WHO subtype, 30% had AML with MRC, 20% NPM1 mutation, 10% inv(3), 10% therapy-related, and 30% not otherwise specified. European LeukemiaNet 2017 risk was favorable in 20%, intermediate in 40%, and adverse in 40%. Median number of cycles completed was 2 [1-7] with a median time on study of 100.5 days [35-678]. One patient achieved CR and 2 achieved CRi for an ORR of 30%. An additional patient likely had a CR with All patients discontinued treatment. Reasons included BMT (40%), AE (30%), progression (20%) and insurance loss (10%). Half planned to bridge to BMT as next-line therapy following study treatment. When taken off study, 50% were alive while 20% had died from AML complications, 20% from graft-versus-host-disease post-BMT, and 10% after relapse post-BMT. Median OS was 6.67 months (95% confidence interval [CI] 6.07 to not reached [NR]). Median EFS was 3.22 months (95% CI 1.50 to NR), with a maximum EFS of 16.93 months. Following G3 PN in the first 2 patients, no DLTs occurred on the modified regimen. Seventy percent of patients experienced at least possibly related G3+ AEs or serious AEs (SAEs). Of the 22 related G3+ AEs, anemia and decreased platelet count were seen in 50% and dizziness in 20%. Of the 22 related SAEs, anorexia, fatigue, PN, febrile neutropenia, and bacteremia were most common, each occurring in 20%. Conclusion The DBP triplet demonstrated preliminary anti-AML activity in a R/R AML patient cohort. Staggered dosing was better tolerated than simultaneous DBP. DBP may serve as an effective bridge to BMT for some patients. This study supports further evaluation of DBP, or related combinations, in R/R AML. Disclosures Rosenberg: Takeda, Janssen: Speakers Bureau. Abedi: Seattle Genetics: Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Speakers Bureau. Tuscano: BMS, Seattle Genetics, Takeda, Achrotech, Genentech, Pharmacyclics, Abbvie: Research Funding. Jonas: AbbVie, BMS, Genentech, GlycoMimetics, Jazz, Pfizer, Takeda, Treadwell: Consultancy; 47, AbbVie, Accelerated Medical Diagnostics, Amgen, AROG, Celgene, Daiichi Sankyo, F. Hoffmann-La Roche, Forma, Genentech/Roche, Gilead, GlycoMimetics, Hanmi, Immune-Onc, Incyte, Jazz, Loxo Oncology, Pfizer, Pharmacyclics, Sigma Tau, Treadwell: Research Funding; AbbVie: Other: Travel reimbursement. OffLabel Disclosure: Bortezomib is FDA-approved for the treatment of multiple myeloma in patients who have already been treated with 2 lines of prior therapy and progressed on the most recent therapy. Decitabine is indicated for treatment of patients with myelodysplastic syndromes. Doxorubicin is approved in AML among other cancers.

BACKGROUND GVHD remains a frequent and serious complication of HSCT despite the decades-long use of standard immunosuppression, such as tacrolimus and methotrexate, as prophylaxis against GVHD. Preclinical models have shown that the timed infusion of donor-derived high-purity CD4+CD25+FOXP3+ regulatory T cells (Treg) preceding adoptive transfer of conventional T cells (Tcon) prevents GVHD and maintains anti-cancer immunity without the need of pharmacologic agents. Early clinical trials using purified Treg-engineered graft showed safety and feasibility, but more extensive clinical studies are needed to test scalability and efficacy. Orca-T is an industry-manufactured, precision-engineered CD34-selected, Treg-engineered graft made in a central GMP laboratory and distributed to multiple centers in the U.S. We present our early patient experience with Orca-T in an ongoing single center phase 2 trial and a multicenter Phase Ib trial and report a pre-planned evaluation of patients randomized to receive Orca-T plus single-agent GVHD prophylaxis (PPX) or Orca-T and no PPX. METHODS 51 patients with high risk or active hematologic malignancies undergoing myeloablative conditioning were enrolled on two trials: a single-center Phase I/II (n=40, NCT01660607) and a multicenter Phase Ib (n=11; NCT04013685) study. Patients received CD34-selected cells infused with highly purified Treg (target dose: 3.0 x 106 cells/kg) followed 2 days later by the infusion of Tcon (3.0 x 106 cells/kg). Initial GMP manufacturing was demonstrated at Stanford (n=9 grafts; 2016 - 2019) and then transferred to Orca Bio in 2019 for scaled production. We evaluated the 34 patients beyond dose escalation since July 2016 who received Orca-T grafts from either matched related (n=25) or unrelated (n=9) donors and single agent GVHD PPX with either tacrolimus (n=28) or sirolimus (n=6). For comparative analysis, we identified a contemporaneous SOC cohort at Stanford (n=138) with both matched related (n=79) and unrelated (n=59) transplant recipients who received unmanipulated PBSC products (median f/u 546 days) and methotrexate plus tacrolimus. In April 2019, enrollment on a phase 2, stage 1 pre-planned subgroup of 24 patients were randomized to test whether all GVHD PPX could be removed: Orca-T plus either single-agent PPX (Arm 1, n=12) or no PPX (Arm2, n=12). RESULTS The Orca-T drug products were manufactured reliably with high Treg purity (93.8% +/- 3.1%) and a dose of 2.6 +/- 0.4 x 106 per kg (equivalent between arms and trials). Central lab turn-around times were 25.3 +/- 3.0 hours and all vein-to-vein times were less than 72 hrs (Table 1). For trial participants, there were no manufacturing failures, engraftment failures or treatment related mortality. Orca-T patients vs. SOC showed earlier neutrophil (median of 11 days vs. 14 days, p Patients across 4 clinical sites received Orca-T plus single agent GVHD PPX (n=34; median f/u 261 days) had an acute GVHD grade 2-4 incidence of 0% as compared to 33% in the SoC cohort (n=138, p=0.0018 by Log-rank Mantel-Cox test, Fig. 1). The rate of moderate to severe chronic GVHD for Orca-T patients was 4% vs. 44% in the SoC cohort (p=0.016). In a preliminary subset of evaluable Orca- T patients, GVHD & relapse free survival (GRFS) at one year was higher for Orca-T patients vs SoC (69% versus 33%, p=0.006) while relapse and overall survival did not appear to differ. We observed no differences in infectious complications. In patients randomized to PPX vs. no PPX, the incidence of aGVHD grade 2-4 was 0% in Arm 1 and 58% in Arm 2 (p CONCLUSIONS Manufacture of high precision Orca-T Treg-engineered donor products were successfully scaled in a central GMP with reliable distribution to centers. Patients who received Orca-T and single agent PPX had no grade 2 or greater acute GVHD acute and very little chronic GVHD when compared to SOC. Patients randomized to Orca-T and no PPX showed an increased incidence of acute GVHD vs. those with Orca-T and single agent PPX. Engineered Treg grafts show promise to improve GFRS and other transplant outcomes. Orca-T has been granted RMAT status by the FDA and evaluation continues in an ongoing multicenter clinical trial. Disclosures Meyer: Orca Bio: Research Funding. Moroz:Orca Bio: Research Funding. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Muffly:Servier: Research Funding; Adaptive: Research Funding; Amgen: Consultancy. Rezvani:Pharmacyclics: Research Funding. Shizuru:Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Fernhoff:Orca Bio: Current Employment, Current equity holder in private company. Putnam:Orca Bio: Current Employment, Current equity holder in private company. McClellan:Orca Bio: Current Employment, Current equity holder in private company. Shaw:Orca Bio: Consultancy. McGuirk:Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Fresenius Biotech: Research Funding; Bellicum Pharmaceutical: Research Funding; Gamida Cell: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Pluristem Ltd: Research Funding. Abedi:BMS, Gilead Sciences: Research Funding; AbbVie, BMS, Gilead Sciences, Seattle Genetics, Takeda: Speakers Bureau. Negrin:Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; KUUR Therapeutics: Consultancy; Biosource: Current equity holder in private company; UpToDate: Honoraria; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company.

Author(s): Esteghamat, Naseem; Keegan, Theresa; Brunson, Ann; Wun, Ted; Abedi, Mehrdad; Tuscano, Joseph; Hoeg, Rasmus; Jonas, Brian; Rosenberg, Aaron

Introduction Adults with newly diagnosed acute myeloid leukemia (AML) who receive intensive remission induction typically remain hospitalized until blood count recovery due to the high risk of infection and bleeding related to pancytopenia. This usually translates into at least 4 weeks of hospitalization, which can lead to reduced quality of life, increased risk of nosocomial infections, significant resource utilization and economic burden. Previous studies conducted at academic centers with large AML populations have suggested that outpatient management following induction chemotherapy is feasible and safe with close follow-up. These studies may have limited generalizability based on exceptional outpatient resources. Thus, this practice has not been widely adopted. To assess the feasibility of early patient discharge at our academic center which provides care for a smaller AML population, where we have a 6-days per week infusion center and hospitalize all AML patients undergoing induction until count recovery, we conducted a retrospective analysis of complications prior to blood count recovery in this patient population. Methods We identified patients ≥18 years with newly diagnosed non-APL AML admitted to the University of California, Davis Medical Center from 1/1/14 to 1/1/19 who received induction chemotherapy with cytarabine/daunorubicin (7+3) or a regimen of similar intensity with first interim bone marrow biopsy showing hypocellularity with Results Overall, 50 patients were identified; 42 (84%) received 7+3, 3 (6%) received FLAG and 5 (10%) received liposomal daunorubicin-cytarabine induction. Median age was 56 (range 25-81) years. ELN 2017 favorable, intermediate and adverse risk disease was observed in 18 (36%), 20 (40%) and 12 (24%) patients, respectively. Forty-nine (98%) patients with a negative interim marrow achieved a complete remission with first induction therapy. Forty-five (90%) patients had infectious complications at any time (Table 1), with 34 (68%) having infectious complications occurring prior to day 15 of induction. All patients with culture negative neutropenic fever prior to day 15 of induction as their only infectious complication had no further infectious complications throughout hospitalization although all received IV antibiotics until count recovery. Ten (20%) patients had hemorrhagic complications at any time (Table 1), with 9 (18%) having hemorrhagic complications occurring between day 15 of induction and discharge. Median platelet transfusion volume between days 15-21 and 22-discharge was 3.5 (range 1-18) and 0 (range 0-15) units, respectively. Three (6%) patients required ICU transfer. All ICU transfers occurred after day 14 of induction. One patient had hypoxic respiratory failure on admission and required transfer back to the ICU. Death prior to marrow recovery was observed in 1 patient (2%) due to subdural hemorrhage. Conclusion Intensive remission induction in hospitalized patients with newly diagnosed AML is associated with good efficacy and safety outcomes for patients with blast clearance on interim bone marrow biopsy. Although the rate of infectious complications was high, the majority debuted early during hospitalization and the rate of ICU transfers was low. All patients with culture negative neutropenic fever prior to day 15 of induction as their sole infectious complication who were treated with IV antibiotics had no further infectious complications throughout hospitalization. Hemorrhagic complications more commonly occurred later during hospitalization, although platelet transfusion requirements were manageable after day 15 of induction. These data suggest that at our institution, select patients receiving intensive remission induction and without infectious complications could be considered for early discharge and close outpatient follow-up after interim bone marrow biopsy showing hypoplasia. A prospective early discharge study to confirm these findings is being developed. Disclosures Poh: Acrotech: Honoraria. Tuscano:Spectrum: Research Funding; Novartis: Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Honoraria. Rosenberg:Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Jonas:Forma: Research Funding; F. Hoffmann-La Roche: Research Funding; Daiichi Sankyo: Research Funding; AROG: Research Funding; Accelerated Medical Diagnostics: Research Funding; Forty Seven: Research Funding; Jazz: Consultancy, Research Funding; Sigma Tau: Research Funding; Hanmi: Research Funding; Genentech/Roche: Research Funding; Pharmacyclics: Research Funding; Celgene: Consultancy, Research Funding; GlycoMimetics: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Treadwell: Consultancy; Tolero: Consultancy; Takeda: Consultancy; Pfizer: Research Funding; LP Therapeutics: Research Funding; Incyte: Research Funding; Amgen: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; AbbVie: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding.

TPS8072 Background: Diffuse large B-cell lymphoma (DLBCL) escapes host immune responses via inhibition of the B2M and CD58 pathways and upregulation of PD-1 ligands. However, treatment results with PD-1 blockade have been disappointing. One potential mechanism is the recruitment of intra-tumoral regulatory T-cells (Tregs) which suppress anti-tumor immunity and inhibit NK cell cytotoxicity. Targeting regulatory T cells with the CCR4 antibody mogamulizumab (KW-0761) represents a molecularly informed strategy to overcome this resistance. Mogamulizumab has been safely administered in combination with pembrolizumab (MK-3475) in patients with solid malignancies and may promote CD8 T-cell dependent effector and NK cell-dependent cytotoxicity in lymphomas. Methods: This is a multi-center NIH-ETCTN phase Ib/randomized phase II study. The phase I will evaluate the safety and tolerability of mogamulizumab in combination with pembrolizumab in patients with R/R DLBCL and determine the recommended phase II dose (RP2D). A traditional 3+3 design with a starting dose of pembrolizumab 200mg IV on day 1 of a 21-day cycle and mogamulizumab 1mg/kg IV on days 1, 8, 15 and then 1.5 mg/kg IV every 21 days. The phase II will evaluate the efficacy of the combination by PFS (primary endpoint) ORR and CR (secondary endpoints). This will be a randomized 1:1 study with allowed crossover, comparing the combination to single agent pembrolizumab Correlative studies will evaluate the association of tumor infiltrating CD8 and NK cells with response to treatment, somatic mutations in B2M and CD58 and with MHC-I expression on DLBCL cells. Functional characterization of circulating immune cells in the peripheral blood and measurement of pro and anti-inflammatory cytokines will be used to assess the levels, activation status and effector function of Tregs and circulating T cells. Inclusion criteria include measurable disease, ≥2 prior lines of therapy including or ineligible for autologous stem cell transplant, ECOG ≤ 2 and normal organ function. Prior or planned allogeneic stem cell transplant, as well as prior treatment with an anti PD-1/PD-L1/CTLA4 antibody, preexisting autoimmune disease or CNS involvement by lymphoma are exclusion criteria. The study aims to enroll up to 12 patients on the phase I and up to 58 patients on the phase II and can be opened at any ETCTN participating site. To date it has been opened at two sites and is accruing the first patients for the phase I portion. Clinical trial information: NCT03309878 .

Introduction: Outcomes remain poor for adults with acute lymphoblastic leukemia (ALL). Hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (Hyper-CVAD) is a high intensity chemotherapy regimen that results in high complete remission (CR) rates and long-term survival in 30-40% of adults with ALL. Approximately 50% of patients achieve measurable/minimal residual disease (MRD) negativity after Hyper-CVAD therapy. Bortezomib, the first proteasome inhibitor, showed potentially synergistic activity in relapsed ALL in combination with chemotherapy. Carfilzomib is a next-generation irreversible proteasome inhibitor with increased specificity and potency compared to bortezomib and with significant activity in multiple myeloma. Therefore, we hypothesized that the addition of carfilzomib to Hyper-CVAD would be safe and could improve outcomes for adults with ALL by increasing the rate of MRD negativity. Methods: The primary objectives of this phase I study (NCT02293109) were to determine safety, tolerability, and recommended phase two dose of carfilzomib added to Hyper-CVAD in patients with newly diagnosed, untreated Philadelphia chromosome negative ALL. The secondary objectives were to determine rate of CR and MRD negativity. Time-to-event analyses were not planned. Patients were aged 18-65 with adequate left ventricular, renal, and liver function and Eastern Cooperative Group Performance Status of 0-2. Patients received four 28-day cycles of standard Hyper-CVAD (i.e. two courses each of Part A and Part B) with the addition of 4 doses of carfilzomib on days 0, 1, 7 and 8 of each of the four cycles. Rituximab was added for patients with CD20 positive disease. After completing study mandated carfilzomib plus Hyper-CVAD, patients continued standard Hyper-CVAD therapy. Dose escalation used a standard 3+3 design with carfilzomib dose levels (DL) of 20mg/m2 (DL1), 27mg/m2 (DL2) and 36mg/m2 (DL3). Dose-limiting toxicities (DTLs) were assessed through completion of one A and one B cycle. Patients not evaluable for DLT were replaced. Adverse events (AEs) were graded using NCI Common Terminology for Adverse Events version 4.03. MRD was tested by multiparameter flow cytometry (MFC) and Results: Ten patients were enrolled into DL1 (n=3), DL2 (n=3), and DL3 (n=4). Median age was 38 [range 23-61]. Fifty percent (n=5) were female, and 60% (n=6) were Hispanic. Eighty percent (n=8) had B-ALL, and 20% (n=2) had T-ALL. Fifty percent (n=5) had CD20 positive disease and received rituximab. Seventy percent (n=7) had abnormal cytogenetics, including complex IgH gene rearrangements (n=4). One patient was found to have CNS involvement during standard cycle one CSF assessments. No DLTs were observed in the dose escalation cohorts. One subject was replaced during cycle one for adverse events not meeting DLT criteria. All patients experienced grade 3-4 treatment-emergent AEs at least possibly related to study therapy, including leukopenia (100%, n=10), neutropenia (100%, n=10), anemia (100%, n=10), thrombocytopenia (100%, n=10), lymphopenia (90%, n=9), and febrile neutropenia (70%, n=7) (Table 1). Serious AEs (SAEs) at least possibly related to study therapy occurred in 70% (n=7) of patients and included febrile neutropenia (60%, n=6), leukopenia (20%, n=2), and thrombocytopenia (20%, n=2). There were no grade 5 events, and no cardiac AEs apart from related grade 1 sinus tachycardia in one patient. The median number of cycles on study was four [range 1-4]. Twenty percent (n=2) of patients had a dose modification (both related to AE), and 30% (n=3) had a dose delay (two related to AE). The complete remission rate (CR) was 90% (9/10) after cycle 2 and 100% (10/10) overall (Table 2). The rate of MFC MRD negativity was 70% (7/10) after cycle 4 and 80% (8/10) overall, including 88% (7/8) for B-ALL and 50% (1/2) for T-ALL (Table 2). There were no study-related deaths. Conclusions: The addition of carfilzomib to Hyper-CVAD is safe and tolerable in patients with untreated ALL. No DLTs were observed with carfilzomib doses up to 36mg/m2. The combination shows promising preliminary efficacy with high rates of MRD negative CR compared to historical controls receiving standard Hyper-CVAD. The regimen may be more active in B-ALL. These results support further study of Hyper-CVAD plus carfilzomib in ALL. Disclosures Jonas: AbbVie, Amgen, GlycoMimetics: Other: Travel expenses; AbbVie, Amgen, Celgene, GlycoMimetics, Jazz, Pharmacyclics, Tolero: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie, Accelerated Medical Diagnostics, AROG, Celgene, Daiichi Sankyo, Esanex, Forma, Genentech/Roche, GlycoMimetics, Incyte, LP Therapeutics, Pharmacyclics: Research Funding. Tuscano:Abbvie: Research Funding; Takada: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Genentech: Research Funding; Pharmacyclics: Research Funding; Spectrum: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Research Funding. Rosenberg:Amgen: Consultancy, Research Funding. Abedi:Abbie: Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Gilead: Speakers Bureau; Celgene: Speakers Bureau. OffLabel Disclosure: Carfilzomib was tested for use in a prospective Phase I clinical trial.

Interventions to change physician transfusion behavior are often evaluated by examining the amount of red blood cell (RBC) units transfused or the proportion of patients transfused before and after the intervention. The pre-transfusion haemoglobin concentration is a sensitive measure of transfusion practice, but has not been used to evaluate behavioral interventions. We examined the effect of a Danish National Board of Health December 2007 transfusion guideline on the behavior of clinicians treating acute myeloid leukaemia (AML). We compared the effect of the guideline on pre-transfusion haemoglobin concentrations with other measures of transfusion behavior, including use of RBC units and proportion of patients transfused. No change in transfusion behavior could be demonstrated by examining amount of RBC units transfused and proportion of patients transfused. Conversely, the pre-transfusion haemoglobin concentration fell significantly. Pre-transfusion haemoglobin determination is a sensitive measure of the effect of an intervention to change physician transfusion behaviour.

Objectives: Translation of evidence-based medicine into oncology practice depends on timely and full publication of clinical trials. We investigated publication outcomes of Phase II trial abstracts from the annual meetings of the American Society of Clinical Oncology (ASCO). Methods: We searched the 1997, 1999, and 2001 ASCO annual meeting proceedings and identified all Phase II trials, excluding those that reported preliminary results. Literature search was performed using PubMed, EMBASE, and Google for corresponding publications in peer-reviewed journals. We attempted to contact authors of all unpublished trials. Results: Only 60.8% of t he 559 trials identified were published, with a median time to publication of 41 months. At 5 years, 65.9%, 62.7%, and 57.0% of studies from 1997, 1999, and 2001, respectively, were published. Studies with larger samples were associated with a shorter time to publication, as were oral and poster presentations versus print only (P < 0.001). Common reasons for not publishing were uninteresting results, lack of time, and relocation of authors. Among abstracts reporting response rates, 37.7% showed different results in subsequent publications. Though not statistically significant, over the 5-year period, abstracts presented at later years had a lower rate of publication, longer time to publication, and a higher likelihood of showing a better tumor response. Conclusions: Almost half of Phase II trials presented at ASCO annual meetings within the last 10 years remain unpublished. Over one-third of published trials reported results different from those presented in abstracts. Like Phase I and III trials, Phase II trials often are unpublished.

Increasingly, hospitalists across the United States provide primary inpatient care for almost all subspecialty patients, including hematology and medical oncology. Febrile neutropenia (FN) is a serious condition often seen as a complication of cytotoxic chemotherapy or in patients with underlying bone marrow defects. The purpose of this study was to document the change of inpatient management of a common admission diagnosis during a transition of providers from hematologists/oncologists to the use of hospitalists in a tertiary care medical center, and to compare the appropriateness of treatment and outcomes over a period of 5.5 years of this transition.The medical records of all patients with neutropenia at a community-based teaching hospital during a period of conversion from hematologist/oncologist to hospitalist coverage were retrospectively reviewed. Patients with fever and absolute neutrophil counts of less than 500/ microL (.5 x 10(9)/L) on admission were included. Study cases were divided into 3 groups by admission date, roughly demarcating the nascent hospitalist era, the era of transition to hospitalist, and the mature hospitalist era. Management of FN during these eras was compared.Three hundred ninety-nine inpatients were identified as neutropenic. Of these, 184 did not meet case-inclusion criteria. The remaining 215 cases were included in the study. The internal medicine hospitalist service admitted less than 10% of this population in 2003, but by 2007-2008 it admitted over 90%. The use of 4th-generation cephalosporins and carbapenems increased over time (P = .027), and the infectious disease service was consulted more frequently over time (P = .007). Outcomes varied due to changes in underlying disease states, use of hospice services, and changes in the types of patients hospitalized with FN. Morbidity decreased due to the change in the type and nonantibiotic therapy of cases, but inappropriate antimicrobial treatment was unusual, and septic morbidity or mortality related to inappropriate therapy was too rare to compare through these eras.Over the 3 eras compared, care of most neutropenic fever patients was transferred from specialists to hospitalists. Care became more uniform, guideline based, and used more infectious disease consultation, and mortality decreased. Complex changes in the types and treatments of cancer, neutropenia therapy, and in the types of patients hospitalized with FN prevent any conclusion of added value for this change in the type of primary provider management.

Background: Distress is an unpleasant psychosocial response that may impede the capacity of patients to cope successfully with a disease, its physical symptoms, and its treatment. Measurements of distress have been extensively evaluated in patients with solid tumor malignancies. The National Comprehensive Cancer Network (NCCN) has recommend standards of care for distress management. However the degree of distress in patients with hematologic diseases (both malignant and non-malignant) is under-investigated. Aim: This study was designed to assess and compare distress in patients with malignant or non-malignant hematological disorders. Methods: Of 617 adult hematology patients enrolled between July 2006 and December 2006, 572 reported distress scores and were prospectively followed, while 45 patients who did not rate their distress were excluded. The NCCN Distress Thermometer (scale of 0–10) accompanied by a modified problem checklist was administered to hematology patients 18 years of age and older seen at the Gundersen Lutheran Center for Cancer and Blood Disorders. Additional demographics, diagnoses, and disease-related information were gathered by chart review. Patients reporting a high score were contacted by a social worker to assess the etiology of distress. Results: At initial visit during the study period, 572 patients reported a distress score (mean = 3.4 ± 2.7). Patients with malignant (3.2 ± 2.7) or non-malignant (3.6 ± 2.6) disease reported similar distress (p = 0.125). Females (4.0 ± 2.8) were more distressed than males (2.9 ± 2.4; p < 0.001). Other factors significantly associated with distress were history of anxiety (p < 0.001), depression (p < 0.001), younger age (p = 0.001), and time from diagnosis (visit day 3.6 ± 2.4; 1–90 days 4.2 ± 2.9; 3mo-1 year 2.9 ± 2.6; 1+ years 3.4 ± 2.7; p = 0.028). Distress based on disease status was (relapse 5.0 ± 3.1, remission/stable 3.3 ± 2.6, treatment 3.7 ± 2.7) also significantly different (p = 0.009). Conclusion: We found no significant difference in levels of reported distress between patients with malignant and non-malignant hematologic disorders. Significantly higher distress levels were reported in women, younger patients, those with previous psychiatric disease, date of visit, and those at relapse. Patients with either malignant or non-malignant hematologic disorders should be considered for distress screening and management.

Background: Angiogenesis and thrombosis, two conditions associated with perturbation of the vascular endothelium and increased CECs, are frequently observed in PV. We performed this study to quantify and characterize CECs in patients with PV and to determine whether CEC profile is associated with thrombotic complications. We also quantified CEPs in a subgroup of patients. Methods: We used flow cytometry to prospectively analyze CECs and CEPs in the whole blood of healthy patients (n=20) and patients with PV (n=30; 13 treated with hydroxyurea, 12 undergoing phlebotomy alone, and 5 never treated). CECs (CD45−/CD31+/CD146+) were quantified and characterized to determine their apoptotic (annexin stain) or activation (CD106+) states. Cells with CD45−/CD31+/CD133+/VEGF-R2+ immunophenotype were considered CEPs. Results: CEC levels in PV patients were higher compared to healthy controls (median 53 cells/mL [range, 11–392] vs 18.5 cells/mL [range, 4–66]; P< .0001). However, the proportions of apoptotic (17.3% [range, 0–87.5] vs 25.9% [range, 0–57.1]; P= .87) and activated (0.7% [range, 0–28.6] vs 0% [range, 0–57.1]; P= .14) CECs were similar between the two groups. In PV patients with high levels (≥2 SD above control mean or ≥53 cells/mL) of CECs (n=14), 5 (36%) developed thromboses. Four (25%) of 16 PV patients with CEC levels similar to healthy controls developed thromboses. The rates of thrombosis between the groups were not statistically different (P= .69). In addition, CEC count, activation, and apoptosis were similar between the hydroxyurea-treated group and the group not treated with hydroxyurea. We detected low numbers of CEPs in PV patients (n=25) that were similar to controls (4 cells/mL [range, 0–100] vs 8 cells/mL [range, 0–60]; P= .34). Conclusions: CECs, but not CEPs, are significantly increased in PV patients. However, there appears to be no association between CEC number, activation or apoptotic state and the development of thromboses. In addition, hydroxyurea therapy does not appear to effect endothelial cells.

6010 Background: Translation of evidence-based medicine into clinical practice depends on timely and full publication of clinical trials. Previous studies have shown that a substantial number of phase I and III trials presented at the annual meetings of ASCO remain unpublished more than 5 years after presentation. We investigated the outcome of phase II trials presented at ASCO. Methods: We searched for phase II trials using the 1997 ASCO Annual Meeting Proceedings. We excluded trials reporting only preliminary data or interim analyses. The following information were extracted from each study: type of presentation, country of origin, sample size, sponsor, treatment modality, novelty of treatment, and efficacy. A literature search was performed using the Medline and EMBASE databases up until January 2006 for full publications in peer-reviewed journals. If a trial was not found, the authors were contacted by E-mail. Results: We identified 124 phase II trials with 13.7%, 30.6%, and 55.6% presented orally, in poster, and in print, respectively. Most trials were either submitted from countries in North America (50.8%) or Europe (34.7%). Funding came from the pharmaceutical companies (24.2%), governments (20.2%), study institutions (15.3%), private foundations (9.7%), or was not specified (30.6%). The top 5 cancers studied were lung, breast, ovarian, gastric, and sarcoma. Treatment included mostly chemotherapy, either alone (87.1%) or in combination with other modalities (3.2%). To date only 70.2% of the trials have been published. The median time to publication for all abstracts was 23 months. The cumulative rates of publication were 12.9%, 34.7%, 51.6%, 64.5%, and 68.5% at 1, 2, 3, 5, and 7 years, respectively. None of the factors we analyzed, including type of presentation, country of origin, sample size, sponsor, novelty of treatment, and efficacy, influenced the likelihood of or time to publication. Conclusions: About a third of phase II oncology clinical trials initially presented as abstracts at the 1997 ASCO annual meeting have not been published almost a decade later. Similar to phase I and III trials, underreporting of phase II trials is an important problem with serious implications for clinical practice that needs to be addressed. No significant financial relationships to disclose.