International Harmonization Project Criteria Research Articles

Prognostic value of interim FDG PET-CT in patients older than 60 years with diffuse large B-cell lymphoma treated by PMitCEBO plus rituximab. Comparison between Deauville 5-point scale and International Harmonization Project criteria.

Advanced age is an independent poor prognostic factor of diffuse large B-cell lymphoma (DLBCL). PMitCEBO (mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone) is an alternative to the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen to decrease side effects in elderly patients. Many studies have shown prognostic value of an interim FDG PET-CT to predict survival. A recent consensus (ICML, Lugano 2013) has suggested using the 5-point scale Deauville criteria instead of those of the International Harmonization Project (IHP) to visually assess the response on interim PET. The objective of this study was to evaluate the prognostic value of an interim FDG PET-CT in patients older than 60 with treated DLBCL and to compare IHP and 5-PS Deauville visual interpretation to predict survival. Forty-eight patients (mean age 73.2±5.2 years) treated by R-PMitCEBO for DLBCL undergoing FDG PET-CT before and after 3 cycles of treatment were retrospectively included. Event-free survival and overall survival were determined by Kaplan-Meier method and compared with interim PET-CT results using IHP and 5-PS Deauville criteria. Interim PET results using 5-PS Deauville criteria were significantly correlated with EFS (P<0.0001) and OS (P=0.001) whereas they were moderately correlated with EFS (P=0.046) and not with OS (P=0.106) using IHP criteria. Two-year EFS and OS rates were 86.5% and 89.2%, respectively, for patients in 1-3 score group, and 27.3% and 36.4%, respectively, for patients in ≥4 score group using the Deauville criteria. Our results confirmed the prognostic value of an interim PET-CT in elderly patients with DLBCL and the better performance of the 5-PS Deauville criteria.

Outcome of Limited Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Evaluation of a PET-Adapted Approach

Outcome of Limited Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Evaluation of a PET-Adapted Approach

Impact of Interim FDG-PET (iPET) in the Outcomes of Patients with Aggressive B-Cell Lymphomas Receiving DA-EPOCH-R

Introduction: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) remains the standard of care for baseline and end of treatment scans for aggressive non-Hodgkin lymphomas (NHLs). However, the role of interim FDG-PET remains not as well defined across aggressive NHLs, especially in the era of high-intensity chemoimmunotherapy. Interim FDG-PET (iPET) can serve as an early prognostic tool, and prior studies evaluating the utility of iPET-guided treatment strategies primarily focused on diffuse large B-cell lymphomas (DLBCL) and frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Classification criteria systems assessing response also differ between studies with no clear consensus between use of Deauville criteria (DC), International Harmonization Project (IHP), and the ΔSUVmax method. Methods: This study evaluates our institutional experience with iPET during treatment with DA-EPOCH ± R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with or without Rituximab) in aggressive NHLs. We retrospectively evaluated 70 patients at Moffitt Cancer Center who started on DA-EPOCH ± R between 1/1/2014 to 12/31/2018 for aggressive NHLs. Response on interim and end-of-treatment (EOT) scans were graded per DC, IHP, and ΔSUVmax methods, and progression free survival (PFS) probability estimates were calculated with chi-square testing and Kaplan Meier method. PFS outcomes were compared between interim negative and positive scans based on each scoring method. Outcomes were also compared between groups based on interim versus EOT positive or negative scans. Results: We identified 70 patients with aggressive NHLs who received DA-EPOCH ± R at our institute. The most common diagnoses were DLBCL (61%) followed by Burkitt's lymphoma (10%), primary mediastinal B-cell lymphoma (9%), plasmablastic lymphoma (7%), gray zone lymphoma (6%), primary cutaneous large B-cell lymphoma (1%), primary effusion lymphoma (1%), and other high-grade NHL not otherwise specified (3%). Of the 43 patients with DLBCL, 21/43 (49%) had double hit lymphoma (DHL) while 7/43 (16%) had triple hit lymphoma (THL), and 3/43 (7%) had MYC-rearranged DLBCL while 2/43 (5%) had double expressor DLBCL. Thirty nine out of 70 (56%) were female, and median age at diagnosis was 58.39 years (range 22.99 - 86.86 years). Most patients had stage IV disease (49/70, 70%), and 43/70 (61%) had more than one extranodal site while 45/70 (64%) had IPI score ≥ 3. Forty-six out of 70 (66%) received central nervous system prophylaxis, most with intrathecal chemotherapy (44/70, 63%). Fifty-five out of 70 (79%) had iPET available while 6/70 (9%) had interim computerized tomography (CT) scans. Fifty-six out of 70 (80%) had EOT PET, and 4/70 (6%) had EOT CT scans. Sustained complete remission occurred in 46/70 (66%) after frontline DA-EPOCH ± R (CR1), and 12/70 (17%) were primary refractory while 5/70 (7%) had relapse after CR1. Four of 70 (6%) died before cycle 3, and 3/70 (4%) did not have long-term follow-up due to transition of care elsewhere. Median follow-up was 15.29 months (range 0.85 - 60.09 months). There was significantly better PFS observed if iPET showed DC 1-3 compared to DC 4-5 (Χ2=5.707, p=0.0169), and PFS was better if iPET was negative by IHP criteria (Χ2=4.254, p=0.0392) or ΔSUVmax method (Χ2=6.411, p=0.0113). Comparing iPET to EOT PET, there was significantly better PFS if iPET was negative with EOT PET negative (iPET-/EOT-) compared to iPET positive with EOT negative (iPET+/EOT-), and iPET+/EOT+ and iPET-/EOT+ had worse PFS after iPET-/EOT- and iPET+/EOT- respectively. This pattern in iPET/EOT PFS probability remained consistent when comparing DC (Χ2=30.041, p&lt;0.0001), IHP (Χ2=49.078, p&lt;0.0001), and ΔSUVmax method (Χ2=9.126, p=0.0104). These findings fit clinical expectations with positive EOT scans indicating primary refractory disease. There was no significant difference in PFS when comparing DLBCL versus non-DLBCL (Χ2=3.461, p=0.0628) or DHL/THL versus non-DHL/THL diagnoses (Χ2=2.850, p=0.0914). Conclusion: Our findings indicate a prognostic role of iPET during treatment with DA-EPOCH ± R for aggressive NHLs. Significant differences in PFS were seen when graded by DC, IHP, and ΔSUVmax methods used in prior studies and when comparing interim versus EOT response. Larger studies are needed to confirm these findings. Disclosures Bello: Celgene: Speakers Bureau. Shah:Novartis: Honoraria; AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Sokol:EUSA: Consultancy. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Interim Circulating Tumor DNA As a Prognostic Biomarker in the Setting of Interim PET-Based Adaptive Therapy for DLBCL

Interim Circulating Tumor DNA As a Prognostic Biomarker in the Setting of Interim PET-Based Adaptive Therapy for DLBCL

Long-Term Follow-up of a PET-Guided Approach to Treatment of Limited-Stage Diffuse Large B-Cell Lymphoma (DLBCL) in British Columbia (BC)

Background: Treatment practices for patients with limited-stage DLBCL are varied and include combined-modality treatment (3 cycles immunochemotherapy + radiation therapy) or immunochemotherapy alone. Since 2005, patients (pts) in BC with limited-stage DLBCL (stage I/II, no B-symptoms, mass &amp;lt; 10cm) have been treated according to a PET-guided algorithm. Following 3 cycles of R-CHOP, pts undergo FDG-PET/CT scan; PET-negative pts receive one additional cycle of R-CHOP, while PET-positive pts receive involved-site radiation therapy (RT). We present long-term follow-up of this population-based experience. Methods: Using the BC Cancer Lymphoid Cancer Database we identified all pts who were diagnosed with limited-stage DLBCL from Mar 2005 to February 2019 and underwent a PET/CT after 3 cycles of curative-intent R-CHOP, in keeping with the PET-guided policy. Pts with primary CNS, primary testicular, PMBCL, PTLD, and transformed/discordant/composite lymphoma were excluded. Pts with evidence of progressive disease prior to or on mid-treatment PET/CT were also excluded. All PET/CT scans were performed and reviewed centrally. Prior to 2014, interpretation was based on the International Harmonization Project (IHP) criteria, and subsequently according to Deauville criteria. Importantly, uptake greater than the mediastinal blood pool was consistently used to determine PET-positivity (ie. PET-positive by IHP, or D3-5 by Deauville). Results: Clinical characteristics of the 319 pts identified are as follows: median age, 68 y (range 19-92); 48%, male; 59%, stage I; 41%, stage II; 8%, PS&amp;gt;1; 13%, elevated LDH; 52%, at least 1 extranodal site; 37%, mass size ≥ 5cm. Stage-modified IPI risk score: 19%, 0; 45%, 1; 27%, 2; 9%, 3-4. Median follow-up is 6.25 yrs (range 0.42-14.25). After 3 cycles of R-CHOP: 254 pts (80%) were PET-negative; 59 pts (18%) were PET-positive; and 6 pts (2%) were considered PET-indeterminate (by IHP). Elevated serum LDH (p&amp;lt;0.001), mass size ≥ 5cm (p=0.008) and stage-adjusted IPI (p=0.025) were predictive of PET-positive status. Of the 254 PET-negative pts, 234 (92%) completed treatment with one additional cycle of R-CHOP, 7 (3%) stopped treatment after 3 cycles R-CHOP and 13 (5%) received RT due to poor chemotherapy tolerance or physician choice. 21/254 PET-negative pts have relapsed and 2/254 died of treatment-related toxicity. 8/21 (38%) PET-negative relapses were late, occurring more than 4 years post initial diagnosis. 55/59 (93%) PET-positive pts received RT, 2 pts refused RT and received only 3 cycles R-CHOP, and 2 pts received 1 additional cycle of R-CHOP alone due to physician preference. 13/59 PET-positive pts have relapsed, only 2/13 (15%) relapses were late &amp;gt;4 years from diagnosis. Of the 6 PET-indeterminate patients, 2 received RT and 3/6 have relapsed. Overall 5-year time-to-progression (TTP) censoring deaths from unrelated causes is 89% (92% for PET-negative and 80% for PET-positive pts). Overall 5-year PFS is 84% (88% for PET-negative and 74% for PET-positive pts) and 5-year OS is 87% (90% for PET-negative and 77% for PET-positive pts). On univariate analysis, age&amp;gt;60, PS&amp;gt;1, stage-modified IPI, and PET status were significant predictors of TTP. On multivariate analysis controlling for age&amp;gt;60, stage, PS, LDH, presence of extranodal involvement, mass size ≥ 5cm, and PET status, only age (p=0.002) and PET status (p=0.004) remained independent predictors of TTP. Conclusion: Using a PET-guided approach to treatment, the majority of patients with limited-stage DLBCL have negative PET scans after 3 cycles of R-CHOP. Patients with negative PET scans have an excellent outcome when treated with 4 cycles of R-CHOP alone, without exposure to radiation. Patients with a positive PET scan who complete treatment with radiation therapy have a slightly less favorable outcome, and may be appropriate for alternative approaches. A detailed analysis of patterns of relapse, as well as efforts to identify clinical factors, PET parameters and biomarkers associated with poor outcome and delayed relapse are ongoing. Figure Disclosures Sehn: Acerta: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria. Scott:NanoString: Patents &amp; Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Abbvie, Sanofi: Consultancy, Honoraria; Astellas Inc.: Research Funding. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria.

Prognostic values of baseline, interim and end-of therapy 18F-FDG PET/CT in patients with follicular lymphoma.

PurposeIn the present study, we aimed to investigate the role of baseline, interim and end-of treatment positron emission tomography/computed tomography (PET/CT) in assessing the prognosis of follicular lymphoma (FL).MethodsA total of 84 FL patients were retrospectively analyzed in this study. Baseline (n=59), interim (n=24, after 2–4 cycles) and end-of treatment (n=43) PET/CT images were re-evaluated, and baseline maximum standardized uptake value (SUVmax), total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG) were recorded. Interim (I-PET) and end-of treatment (E-PET) PET/CT responses were interpreted by Deauville five-point scale (D-5PS) and International Harmonization Project criteria (IHP). Survival curves were calculated by Kaplan-Meier curves, and differences between groups were compared by log-rank test.ResultsThe 2-year progression-free survival (PFS) of the high- and low-TLG groups was 57.14% and 95.56%, respectively (p=0.0001). The 2-year overall survival (OS) of the high- and low-TLG groups was 62.50% and 100%, respectively (p<0.0001). Multivariate analysis showed that TLG was an independent prognostic factor for PFS (p=0.001, HR=6.577, 95% CI=2.167–19.960) and OS (p=0.030, HR=19.291, 95% CI =2.689–137.947). Besides, Eastern Cooperative Oncology Group (ECOG) was the independent prognostic factor for OS (HR=8.924, 95% CI=1.273–62.559, p=0.028). Interim PET results based on D-5PS or IHP criteria were not significantly correlated with PFS (all p>0.05). However, E-PET results using D-5PS and IHP criteria were statistically significant (p=0.0001 and p=0.006). The D-5PS showed stronger prognostic value compared with IHP criteria. The optimal cutoff value of ΔSUVmax% was 66.95% according to I-PET and 68.97% according to E-PET. However, only the ΔSUVmax% from the baseline to the end-of therapy yielded statistically significant results in the prediction of PFS (p=0.0002).ConclusionOur findings indicated that the baseline TLG and E-PET results were significantly associated with prognosis in patients with FL.

FDG-PET/CT at the end of immuno-chemotherapy in follicular lymphoma: the prognostic role of the ratio between target lesion and liver SUVmax (rPET).

To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with follicular lymphoma (FL) submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to compare rPET with International Harmonization Project criteria (IHP), Deauville Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI). Eighty-nine patients with FL undergoing PI-PET were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point of rPET with respect to 5-years progression free survival (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of adverse events as gold standard. The ROC analysis for rPET as predictor of progression showed an optimal rPET cut-point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50, 30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS and rPET differed only in two patients. FLIPI was not predictive of progression and relapse. rPET is a prognostic factor in patients with FL submitted to PI-PET. Although it has a similar prognostic power as DS, it can have methodological advantages over visual analysis. PI-PET with different evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it could be useful to identify patients with FL at risk for early relapse after immuno-chemotherapy.

Predictive approaches for post-therapy PET/CT in patients with extranodal natural killer/T-cell lymphoma

The aim of this study was to assess the prognostic capacity of three methods of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT analysis carried out after therapy in patients with extranodal natural killer/T-cell lymphoma (ENKTL). The three methods of PET/CT analysis included the International Harmonization Project (IHP) criteria, the Deauville five-point scale (5-PS), and standardized uptake value (SUV)-based assessment. Fifty-nine patients diagnosed with ENKTL were enrolled. Each patient underwent three F-FDG PET/CT scans: (i) baseline, (ii) after two to four cycles of chemotherapy (early response assessment), and (iii) at the end of treatment (evaluation of the final response). Post-therapy F-FDG PET/CT results were determined on the basis of IHP criteria, 5-PS, and change in the maximum F-FDG uptake (ΔSUVmax). IHP criteria, 5-PS, and ΔSUVmax were then examined for their ability to predict progression-free survival (PFS) and overall survival (OS). Over a median follow-up of 25 months, 5-PS and ΔSUVmax were significant predictors of PFS and OS. After multivariate analysis, 5-PS could predict PFS (P=0.008) and OS (P=0.002) independently. ΔSUVmax was found to be an independent predictor of PFS (P=0.019), but not OS, and had a lower accuracy and positive predictive value than 5-PS. Post-therapy PET/CT analysis using the 5-PS is more able to predict survival than analysis with IHP or [INCREMENT]SUVmax in ENKTL patients.

Predictive value of interim PET/CT visual interpretation in the prognosis of patients with aggressive non-Hodgkin's lymphoma.

ObjectiveThe objective of the study was to evaluate the prognostic value of positron emission tomography (PET)/computed tomography (CT) visual interpretation in patients with aggressive non-Hodgkin’s lymphoma (NHL) using a meta-analysis and systematic review.MethodsUsing the PubMed, Embase, and Web of Science databases, we performed a systematic review of the use of visual evaluation mid-chemotherapy to evaluate the prognosis of aggressive NHL in studies published up to May 2017. Prospective and retrospective studies assessing progression-free survival (PFS) and overall survival (OS) were included. We used hazard ratio (HR) to determine the value of Deauville criteria and International Harmonization Project (IHP) criteria for measuring survival. Subgroup analysis was performed based on the number of chemotherapy cycles before the mid-term evaluation as well as the visual evaluation method.ResultsA total of 11 studies were included. PFS (HR =2.93, 95% confidence interval [CI]: 2.93–3.90, p<0.0001) and OS (HR =2.55, 95% CI: 1.76–3.68, p<0.0001) of PET/CT-positive patients were significantly lower when determined by the visual method. In subgroup analysis, IHP, Deauville criteria, and having no standard interpretation groups were factors able to predict PFS; IHP and having no standard interpretation group were able to predict OS. With PET/CT, IHP, and Deauville 5-point criteria, the PFS of patients receiving 2–4 cycles of chemotherapy before PET/CT was significantly lower than that of PET/CT-negative patients. No significant difference in OS was observed when patients received 3 or fewer cycles of chemotherapy before PET/CT, though OS was significantly lower in patients receiving more than 3 chemotherapy cycles.ConclusionIHP and Deauville criteria are commonly used for PET/CT visual evaluation at present. Interim PET/CT analysis after 3–4 chemotherapy cycles is capable of predicting disease prognosis. Large-scale prospective clinical trials are needed to confirm whether PET/CT analysis can be used as an indication for changing a treatment strategy.

FDG-PET–driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study

AbstractDose-dense induction and up-front consolidation with autologous stem cell transplantation (ASCT) remain controversial issues when treating patients with high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and centrally assessed using international harmonization project (IHP) criteria. PET2−/PET4− patients were assigned SIC, PET2+/PET4− patients were assigned ASCT, and PET4+ patients were treated with the investigator's choice. The primary end-point was the 2007 international working group complete response (CR) rate after induction. Change in maximum standard uptake value (ΔSUVmax) after PET assessment was explored. Two hundred eleven patients were randomly assigned to R-ACVBP (n = 109) or R-CHOP14 (n = 102). PET4−/CR rates were 53%/47% with R-ACVBP and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%, respectively; P = .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively. PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; P = .08), leading to more salvage therapy (37% vs 26%; P = .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; P < .01), but progression-free survival (PFS) and overall survival (OS) were similar in both groups. PET2−/PET4− and PET2+/PET4− patients had similar outcomes. Using ΔSUVmax, 79% of the patients were PET2−/PET4−. ΔSUVmaxPET0-4 >70% was associated with better outcome (4-year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; P < .0001), whatever the consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria did not properly reflect disease control. ΔSUVmax may help better select patients needing an alternative to SIC, including ASCT.

Interim PET-CT may predict PFS and OS in T-ALL/LBL adult patients.

T lymphoblastic leukemia/lymphoma (T-ALL/LBL) is highly aggressive. Although intensive chemotherapies such as ALL-type regimens are commonly used, about half adult patients eventually relapse and die of T-ALL/LBL. Overwhelming evidences have confirmed that interim PET can predict survival outcomes and guide subsequent treatments in Hodgkin lymphoma. However, whether interim PET-CT can predict survival outcomes or not in T-ALL/LBL patients remains unclear. 47 adult patients of T-ALL/LBL were retrospectively reviewed. Interim PET-CT was done after induction therapy and evaluated according to the International Harmonization Project criteria. After induction therapy, interim PET-CT was positive in 19 patients (40.4%). After a median follow up time of 34 months, the 2-year and 3-year progression free survival (PFS) rate were 39% and 30%, respectively, and the 2-year and 3-year overall survival (OS) rate were 54% and 45%, respectively. Using Kaplan-Meier survival analysis, it was found that interim PET-CT positivity correlated with significantly inferior PFS and OS (2-year PFS rate for patients with positive or negative interim PET were 21.1% or 56.0%, respectively, p = 0.002; 2-year OS rate for patients with positive or negative interim PET were 31.6% or 63.7%, respectively, p = 0.010). However, there was no significant relationship between PFS, OS and bone marrow infiltration, lactate dehydrogenase level, and stages (p > 0.05). Interim PET-CT may predict PFS and OS in adult patients of T-ALL/LBL, which needs to be validated in prospective clinical trials. The optimal criteria for interim PET-CT evaluation and risk-adapted treatment strategy determined by interim PET-CT should be investigated in future clinical practice.

Prediction of outcome in pediatric Hodgkin lymphoma based on interpretation of 18FDG-PET/CT according to ΔSUVmax, Deauville 5-point scale and IHP criteria.

Minimizing side effects by using response-adopted therapy strategies plays an important role in the management of pediatric Hodgkin lymphoma (HL); however, the criteria for the definition of adequate or inadequate response are controversial. The aim of this study is to compare different methods of interpretation of 18F-FDG-PET/CT (PET) in the prediction of disease outcome in order to determine the optimum method in this regard. Baseline, interim and post-treatment PET scans of 72 children were interpreted according to revised International Harmonization Project criteria (IHP) and Deauville criteria. Cut-off values for changes in interim and post-treatment FDG uptake (ΔSUVmax) in the prediction of progression-free survival (PFS) were measured using ROC analysis. Quantitative and visual data were compared with each other in the prediction of PFS. Mean interim and post-treatment ΔSUVmax of the primary lesions were 77.4±19.5 and 68.8±30.4% and respective cut-off values were 82 and 73%. However, only post-treatment ΔSUVmax yielded statistically significant results in the prediction of 3-year PFS (p=0.043). Interim ΔSUVmax was further analyzed according to the values reported in the literature (66 and 77%) yet statistically significant results were not reached (p=0.604 and 0.431). For interim evaluation, IHP criteria was correlated to Deauville criteria (p=0.002 and p=0.001) and ΔSUVmax (p=0.03), whereas for post-treatment evaluation, significant correlation with ΔSUVmax (p=0.04) but marginally significant (p=0.055 and p=0.058) correlation with Deauville criteria were achieved. Overall, 1, 3 and 5-year PFS were 95.7±0.2, 89.6±0.4 and 80.8±0.7%, respectively. All methods demonstrated comparable performance in the prediction of 3-year PFS; however, interim PET using Deauville criteria and post-treatment PET using IHP criteria were statistically significant. All methods demonstrated high negative-predictive value but substantially low positive-predictive value. Deauville criteria are superior to other methods in the prediction of pediatric HL outcome using interim PET data. On the other hand, quantitative evaluation and visual evaluation by IHP can be used reliably at the end of the treatment. In this regard, we report the optimal cut-off value of SUVmax reduction as 73%.

FDG PET/CT response in diffuse large B-cell lymphoma: Reader variability and association with clinical outcome.

F-18-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is essential for monitoring response to treatment in patients with diffuse large B-cell lymphoma (DLBCL) and qualitative interpretation is commonly applied in clinical practice. We aimed to evaluate the interobserver agreements of qualitative PET/CT response in patients with DLBCL and the predictive value of PET/CT results for clinical outcome.PET/CT images were obtained for patients with DLBCL 3 times: at baseline, after 3 cycles of first-line chemotherapy (interim), and after completion of chemotherapy. Two nuclear medicine physicians (with 3 and 8 years of experience with PET/CT) retrospectively assessed response to chemotherapy blinded to the clinical outcome using International Harmonization Project (IHP) criteria and Deauville 5-point score. The associations between PET/CT results and progression-free survival (PFS) and overall survival (OS) were assessed using Cox regression analysis.A total of 112 PET/CT images were included from 59 patients with DLBCL (36 male, 23 female; mean age 53 ± 14 years). Using the IHP criteria, interobserver agreement was substantial (Cohen κ = 0.76) with absolute agreement consistency of 89%. Using the Deauville score, interobserver agreement was moderate (Cohen weighted κ = 0.54) and absolute consistency was 62%. The most common cause of disagreements was discordant interpretation of residual tumor uptake. With median follow-up period of 60 months, estimated 5-year PFS and OS were 81% and 92%, respectively. Neither interim nor posttreatment PET/CT results by both readers were significantly associated with PFS. Interim PET/CT result by the more experienced reader using Deauville score was a significant factor for OS (P = 0.019).Moderate-to-substantial interobserver agreement was observed for response assessments according to qualitative PET/CT criteria, and interim PET/CT result could predict OS in patients with DLBCL. Further studies are necessary to further standardize the PET/CT-based response criteria for more consistent interpretation.

Predictive Value of Interim 18 f-FDG PET-CT Scans on Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Study

18 F-PET-CT is clinically recommended for monitoring therapeutic response in DLBCL patients. But the role of interim PET-CT remains controversial, and most of the previous researches were retrospective. We designed this study to prospectively evaluate whether interim PET-CT was a valid prognostic tool for patients with DLBCL treated with R-CHOP regimen and if yes, try to determine the more appropriate time and interpretation method for interim PET-CT.This study was a sub-study of the parental study "A prospective, multicenter randomized phase III clinical trial of intensified chemotherapy in improving the treatment efficacy of patient with diffuse large B-cell lymphoma" (NCT01793844). The sub-study included patients that have already been enrolled in the parent study at Sun Yat-Sen University Cancer Center prospectively. Patients were evaluated with PET-CT scans before treatment and after every 2 cycles of R-CHOP and after the completion of first-line treatment. Regular follow-up starts from the enrollment.Between Jan. 2008 and Aug. 2014, 221 patients in Sun Yat-Sen University Cancer Center were enrolled in this sub-study, among whom 203 patients were included in the analysis and the other 18 were excluded for lacking the necessary raw data of PET-CT scan. PET evaluation would be applying the visual criteria of International Harmonization Project(IHP) and the Deauville 5-point scale(5-PS). The results showed PET positive in 103 patients and negative in 100 patients after 2 cycles of R-CHOP chemotherapy with IHP criteria. Among the 103 patients with positive PET-2, 53 patients turned negative after 4 cycles of chemotherapy and still 50 patients remain positive. At the evaluation of end-of-first-line-treatment, 165 patients achieved CR, while 30 achieved PR and 8 PD . According to 5-PS criteria, 146 patients were PET negative with 57 were positive after 2 cycles of chemotherapy. And 173 patients were negative in PET-4 evaluation, while 30 patients remained positive. With a median follow-up of 25.46 months (range 3.60~77.33 months) and according to IHP criteria, patients with negative PET-2 had superior 3-year PFS (84.7% vs. 63.8%, p < 0.001) and OS (89.8% vs. 80.4%, p = 0.045) than those with positive results. Patients with negative PET-4 also had a better clinical outcome compared with the positive group with 3-year PFS (84.1% vs. 43.8%, p < 0.001) and OS (90.7% vs. 67.8%, p < 0.001). A further analysis showed that patients who achieved PET negative just after 2 cycles of chemotherapy (Early responder, ER) had a similar prognosis comparing with those who achieved PET negative after 4 cycles (Later responder, LR). There were no significant differences in the persistent CR rates (87.00% vs. 86.79%, p = 0.971), 3-year PFS (84.7% vs. 82.2%, p = 0.867) and 3-year OS (89.8% vs. 92.9%, p = 0.638) between the ER group and the LR group. Patients who remained PET positive after 4 cycles of chemotherapy (Interim non-responder, I-NR) had the worst prognosis. Their persistent CR rate (42.00% vs. 87.00%, p < 0.001; 42.00% vs. 86.79%, p < 0.001), 3-year PFS (43.8% vs. 84.7%, p < 0.001; 43.8% vs. 82.2%, p < 0.001) and 3-year OS (67.8% vs. 89.8%, p < 0.001; 67.8% vs. 92.9%, p = 0.002) were significantly lower, comparing with the ER and LR group. And according to 5-PS criteria, the results were similar. Patients with negative PET-2 had superior 3-year PFS (82.9% vs. 51.6%, p < 0.001) and OS (89.7% vs. 72.9%, p = 0.001) than those with positive results. Patients with negative PET-4 also had a better clinical outcome compared with the positive group with 3-year PFS (81.8% vs. 30.0%, p < 0.001) and OS (90.1% vs. 54.2%, p < 0.001). In the multivariate analysis, PET-4 with IHP criteria, PET-4 with 5-PS criteria and IPI score were independent predictive factors for PFS of patients with DLBCL. A further analysis of positive predictive value (NPV) and negative predictive value (PPV) showed PET-4 was superior than PET-2, especially interpretated with 5-PS. The PPV and NPV of PET-4 with 5-PS criteria were 70.00% and 83.82% respectively.These data indicates that Interim 18 F-FDG PET-CT scan could predict the prognosis of DLBCL patients treated with R-CHOP regimen. And it was recommended that interim 18 F-FDG PET-CT scan be done after 4 cycles of chemotherapy, and that 5-PS criteria be applied in the interpretation of interim PET-CT scan rather than IHP criteria. DisclosuresNo relevant conflicts of interest to declare.

Early Treatment Intensification with R-ICE Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) Using Zevalin-BEAM for Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) As Identified By Interim PET/CT Scan Performed after Four Cycles of R-CHOP-14: A Multicenter Phase II Study of the Australasian Leukaemia Lymphoma Study Group (ALLG)

Early Treatment Intensification with R-ICE Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) Using Zevalin-BEAM for Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) As Identified By Interim PET/CT Scan Performed after Four Cycles of R-CHOP-14: A Multicenter Phase II Study of the Australasian Leukaemia Lymphoma Study Group (ALLG)

FDG PET/CT Response Assessment Criteria for Patients with Hodgkin's and Non-Hodgkin's Lymphoma at End of Therapy: A Multiparametric Approach.

Based on the International Harmonization Project (IHP) criteria, positron emission tomography (PET) response assessment of residual nodal masses in patients with lymphoma after completion of therapy is performed visually using mediastinal blood pool as the reference. The primary objective of this study was to define the optimal reference for PET response assessment. Secondary aim was to assess if morphological criteria on computed tomography (CT) may improve performance of PET. This institutional review board approved retrospective study included 137 patients, with Hodgkin's (n = 43) or non-Hodgkin's lymphoma (n = 94) assessed for residual masses (n = 180) after completion of therapy with pathology and clinical and imaging surveillance data (mean, 19months) as the standard of reference. Two readers independently assessed response by IHP and Deauville criteria. The addition of morphological parameters on CT was assessed in relation to therapy response. Based on the standard of reference, 36 patients (26.3%) had residual lymphoma. For IHP and Deauville criteria, sensitivity, specificity and accuracy were 97.2%, 97.2% (p = 1); 79.2%, 92.1% (p < 0.001); and 83.9%, 93.4% (p = 0.001), respectively. Of the morphological parameters assessed, only change in size over course of therapy was significant (p < 0.003) and improved specificity for IHP-based interpretation to 90.4% (p = 0.008). Using liver as the visual reference to determine PET positivity for lymphoma patients being assessed for residual masses at the end of therapy improves specificity, yet maintains the high sensitivity of PET in identifying residual disease. The addition of change in size after therapy improves specificity of PET when using IHP-based but not Deauville-based interpretation.

Predictive Value of Interim 18f-FDG PET-CT Scans on Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Study of Chinese Southwest Oncology Group (CSWOG)

Purpose18F-FDG PET-CT has been widely used for pre-treatment staging and post-treatment response assessment in diffuse large B cell lymphoma (DLBCL), but the predictive value of interim PET-CT remained controversial and most of studies were retrospective.Patients and MethodsNewly-diagnosed DLBCL patients treated with R-CHOP regimen were included in our prospective study to evaluate the predictive value of interim PET-CT. All patients were evaluated with PET-CT scans before treatment and after every 2 cycles of R-CHOP. PET-CT positivity or negativity was related to survival using Kaplan-Meier analysis.ResultsFrom Feb 2008 to Jan 2013, 149 patients were included. After 2 cycles of R-CHOP, the PET-CT evaluation showed CR in 82 patients. Among the remaining 67 non-CR patients, 31 achieved CR after 4 cycles. At the end of treatment, PET-CT evaluation showed CR in 121, PR in 21, SD in 3 and PD in 4 patients. With a median follow-up of 20.6 months (range 1.5-60.5 months), patients with negative PET-2 (PET-CT scan after 2 cycles) had a superior 2-year PFS than those with positive PET-2 (86.6% vs. 67.0%, p=0.019) and a tendency of superior 2-year OS without statistical differences (91.9% vs. 85.2%, p=0.330). The 2-year PFS and OS for negative PET-4 (PET-CT scan after 4 cycles) compared with positive PET-4 group were 84.8% vs. 51.9% (p=0.001) and 93.1% vs. 73.0% (p=0.027) respectively. PET-CT scans were interpreted using the International Harmonization Project (IHP) criteria above. The second analysis applying the Five-Point Scale (5PS) criteria showed that 2-year PFS for score 1-2 (uptake＜mediastinum), score 3 (mediastinum＜uptake≤liver) and score 4-5 (uptake＞liver) group were 86.6%, 75.8% and 71.0% according to PET-2, and 84.9%, 50.0% and 52.7% according to PET-4. PFS of score 3 group was not significant different from the other two groups in PET-2 (both P＞0.05), but significantly inferior to score 1-2 group (p=0.046) and similar to score 4-5 group (p=0.767) in PET-4. In the multivariate analysis, only PET-4 (95%CI, 1.07-5.44) and IPI score (95%CI, 1.53-10.06) remained independent predictive factors for PFS.ConclusionPET-CT after 4 cycles of R-CHOP in patients with DLBCL is highly predictive of PFS and should be considered in clinical practice.(Clinical Trail Registration Number: CTR-TRC-11001687) DisclosuresNo relevant conflicts of interest to declare.

Phase 2 Trial of Interim PET Scan-Tailored Therapy in Patients with Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL) in British Columbia (BC)

Introduction: While the majority of patients (pts) with advanced stage DLBCL will be cured with R-CHOP, pts who fail front-line therapy continue to have a dismal outcome. Optimization of initial therapy remains an important goal. Interim PET scanning has been demonstrated to be prognostic in DLBCL and may be a promising tool to select pts in whom alternate non-cross-resistant therapies should be considered prior to the emergence of further drug resistance. With this rationale, a phase 2 trial was initiated to assess the feasibility and efficacy of PET-tailored therapy for DLBCL within the province of BC. Methods: This phase II trial was conducted at multiple sites within the BC Cancer Agency. Patients >17 years of age with biopsy proven de novo advanced stage DLBCL, including PMBCL (stages 3 and 4, or stages 1 and 2 with B-symptoms or bulky mass > or = 10cm), with an ECOG PS Results: 155 patients were enrolled between Oct 2006 and May 2014. Patient characteristics: median age 53 y (range 19-79); 54% male; 105 (68%) stages 3 or 4; 52 (34%) age >60 y; 55 (35%) ECOG PS >1; 90 (60%) elevated LDH; 44 (28%) extranodal sites >1; 81 (52%) bulky mass ³10cm; and 65 (42%) IPI score 3-5. 2 patients were non-evaluable: no interim PET due to toxicity (n=1), withdrawal (n=1). 3 pts were taken off study due to progression on R-CHOP. Of the 150 evaluable pts with interim PET, 88 (59%) were PET-neg, 50 (33%) were PET-pos and 12 (8%) were PET-ind. PET-pos pts were more likely to have elevated LDH and bulky disease at diagnosis. All PET-neg pts completed treatment with R-CHOP as intended and none received XRT. Of the 50 PET-pos pts, 2 refused to switch to R-ICE and completed treatment with R-CHOP (both received XRT). 48/50 PET-pos pts proceeded to R-ICE: 9 pts failed to complete all 4 cycles R-ICE due to toxicity and 6/9 switched back to R-CHOP; 3 progressed during R-ICE and did not have a final PET scan. The remaining 36/50 PET-pos pts completed 4 cycles R-ICE and underwent a final PET: 11/36 had a negative PET post R-ICE (2 received XRT, regardless); 25/36 had a positive PET post R-ICE (12 received XRT). Of the 12 PET-ind pts, 10 completed treatment with R-CHOP (1 with XRT), while 2 were switched to R-ICE (no XRT). With a median follow-up time of 45 mos, 4-y PFS and overall survival (OS) for the evaluable cohort were 79% and 87%, respectively. PET-neg pts had a very favorable outcome (4-y PFS 91%, 4-y OS 96%), whereas PET-pos pts had a less favorable outcome (4-y PFS 59%, 4-y OS 73%). PET-ind pts had an intermediate outcome with 4-y PFS 83% and 4-y OS 82%. Conclusions: While PET-tailored therapy in pts with advanced stage DLBCL was feasible in BC, approximately 20% of patients were unable to tolerate the planned 4 cycles of R-ICE due to various toxicities, mainly myelosuppression. Pts who were PET-neg following 4 cycles of R-CHOP had an excellent outcome, without need for XRT. PET-pos pts had a poorer outcome, but did better than expected compared to historical reports. However, relatively few PET-pos pts converted to a negative PET scan following R-ICE, suggesting that simply switching to this alternate non-cross resistant chemotherapy regimen is insufficient to overcome the inherent resistance in this poor risk population. Disclosures Sehn:Roche/Genentech: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Off Label Use: Use of R-ICE chemotherapy in front-line therapy of DLBCL.. Hardy:Roche Canada: Research Funding. Gill:Roche Canada: Research Funding. Al-Tourah:Roche Canada: Research Funding. Shustik:Roche Canada: Research Funding. Macpherson:Roche Canada: Research Funding. Yee:Roche Canada: Research Funding. Lam:Roche Canada: Research Funding. Savage:Roche Canada: Research Funding. Klasa:Roche Canada: Research Funding. Villa:Roche Canada: Research Funding. Gerrie:Roche Canada: Research Funding. Shenkier:Roche Canada: Research Funding. Slack:Roche Canada: Research Funding. Gascoyne:Roche Canada: Research Funding. Benard:Roche Canada: Research Funding. Wilson:Roche Canada: Research Funding. Tonseth:Roche Canada: Research Funding. Connors:Roche Canada: Research Funding.

Combined Use of Interim Positron Emission Tomography Scans and Serum Soluble Interleukin-2 Receptor Values Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma

<Background> The prognostic impact of interim positron emission tomography scans (I-PET) for patients with diffuse large B-cell lymphoma (DLBCL) is a matter of debate because its positive predictive value (20–80%) is low. Here, we aimed to improve the prognostic impact of I-PET by combining it with interim analysis of serum soluble interleukin-2 receptor (sIL2R) levels, the levels of which at the time of diagnosis are associated with the prognosis of DLBCL.<Patients and Methods> We retrospectively examined data from DLBCL patients diagnosed at our institution between January 2006 and October 2013. Patients were included in the analysis if they met all of the following criteria: six or more cycles of rituximab plus CHOP regimen (R-CHOP); I-PET performed after 2-4 cycles of chemotherapy; and sIL2R levels measured after each cycle. Patients with primary central nervous system lymphoma, primary mediastinal large B-cell lymphoma, or transformed DLBCL from indolent lymphoma were excluded. I-PET was assessed visually according to the International Harmonization Project criteria. The interim sIL2R (I-IL2) level was defined as the value measured just before the fourth R-CHOP cycle. I-IL2 levels > 800 U/ml, or 2000 U/ml if serum creatinine was > 2.0 mg/dl (sIL2R is influenced by renal function), were regarded as positive. The primary endpoint of the study was progression-free survival (PFS). The unadjusted probabilities of PFS were estimated using the Kaplan-Meier method. The log-lank test and multivariate Cox regression analysis were used to assess the prognostic values of each clinical variable.<Results> In total, 135 patients were enrolled. The median age was 66 years (range, 34–89) and 66 patients (48.9%) were male, 27 (20%) had an ECOG performance status >1, 18 (13.3%) had bulky disease, 81 (60%) had advanced disease, and 61 (45.2%) had a high or high-intermediate International Prognostic Index (IPI) score. The median follow-up time was 25.6 months (range, 6.3–88.7) and the 2 year progression-free survival rate (2-y PFS) of the entire cohort was 72.9% (95% confidence interval (CI), 63.8–80). I-PET and I-IL2 were positive in 47 (34.8%) and 15 (11.1%) patients, respectively. Univariate analysis revealed that a high IPI score, a positive I-PET, and a positive I-IL2 had statistically significant poor prognostic effects on PFS, although gender and bulky disease did not. The three significant variables were entered into multivariate analysis, which identified positive I-PET and I-IL2 values (but not IPI) as independently associated with a poor prognosis. The 2-y PFS was 81.8% (95% CI, 70.4–89.1) for I-PET-negative and 56.3% (95% CI, 40.7–69.3; p<0.001, log rank test) for I-PET positive, respectively. Although a negative I-PET was highly predictive of a favorable outcome, a positive I-PET was of limited clinical value. The 2-y PFS for the 13 patients (9.6%) that were both I-PET- and I-IL2-positive was significantly lower than that of the remaining patients (27.7% [95% CI, 7.1–53.6] and 77.7% [95% CI, 68.4–84.6], respectively; p<0.001). Patients that were positive for both I-PET and I-IL2, rather than patients that were positive for I-PET alone, had a poor outcome.<Conclusion> DLBCL patients that were both I-PET- and I-IL2-positive suffered a high rate of progression; therefore, such patients should be targeted by novel therapeutic approaches. Because the study was based on a retrospective analysis and a limited follow-up period, further studies are needed to confirm the prognostic impact of the combined use of I-PET and I-IL2. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Phase II Study of MLN8237 (Alisertib) Alone and in Combination with Rituximab in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas (NHL)

Introduction: Aurora A kinase is a serine-threonine kinase important in the cell cycle. Overexpression of Aurora A kinase has been associated with the development of NHL with Aurora A kinase activity amplified in aggressive NHL. Alisertib is an orally bioavailable Aurora A kinase inhibitor that targets a key molecule in the cell cycle of dividing cells that leads to mitotic spindle defects and apoptosis. Due to demonstrated pre-clinical and early clinical efficacy of Alisertib in the treatment of B-cell NHL, we conducted a phase 2 trial with Alisertib alone and in combination with rituximab in patients with relapsed aggressive and indolent NHL.Methods: Patients ≥ 18 years with relapsed or refractory B-cell NHL including follicular lymphoma (FL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia (LPL/WM), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) who had received one prior therapy and transformed NHL (tNHL) at any time after diagnosis of transformation were eligible. Additional eligibility included ECOG Performance Status 0-2, adequate renal and liver function, absolute neutrophil count (ANC) ≥ 1000/µL and platelets ≥ 75,000/µL. Patients with indolent NHL (FL, MZL or LPL/WM) were accrued to Cohort A and all other patients (MCL, DLBCL, BL and tNHL) were accrued to Cohort B. Patients treated on Cohort A received Alisertib at a dose of 50 mg twice daily (BID) for days 1-7 of 21 day cycles with rituximab (375 mg/m2) added on day 1 of cycles 5-12 in patients who failed to achieve a complete response (CR) after cycle 4. Patients treated on Cohort B received Alisertib at a dose of 50 mg BID for days 1-7 of 21 day cycles with rituximab added on day 1 of cycles 3-10 in patients who failed to achieve a partial response (PR) or CR after cycle 2 and on day 1 of cycles 5-12 in any patient remaining on monotherapy who had not achieved a CR after cycle 4. Response was assessed according to the International Harmonization Project criteria (Cheson, JCO 2007) and patients were evaluated by imaging after cycle 2, 4, 6 and after every 3 cycles thereafter. Toxicity was assessed per NCI CTCAE v4.0.Results: Eleven patients were enrolled in this trial, 1 patient in Arm A with FL and 10 patients in Arm B with DLBCL (n=6), primary mediastinal DLBCL (n=1), and tNHL (n=3). The median age was 58 years (range 35-77); 10 patients had Stage III-IV disease; the median number of prior therapies was 4 (range 2-6); and 5 patients had prior autologous stem cell transplant. Patients received a median of 2 treatment cycles (range 1-5). Two patients in Cohort B received rituximab added on day 1 of cycle 3 for SD. Grade 3/4 adverse events included grade 3 neutropenia (36%), grade 3 fatigue and dehydration (18%), grade 3 mucositits (9%), grade 3 cystitis (9%), grade 3 pancreatitis (9%), grade 3 pneumonitis (9%) and grade 3 thromboembolic disease (9%). One patient required dose reduction for mucositis, 1 patient went off study for pneumonitis, 1 patient went off study due to patient preference and 8 patients came off study for PD. The overall response rate was 9%, with 1 patient achieving a partial response (PR). This patient had Stage IV CD5+ DLBCL with 2 prior therapies. The patient had SD after 2 cycles and rituximab was added, with response improving to a PR after 5 cycles. The patient went off study after 5 cycles to proceed with allogeneic stem cell transplantation and remains in remission 262 days post-transplant.Conclusions: In this heavily pre-treated, high-risk population of patients with relapsed/refractory NHL, the oral agent Alisertib was overall well tolerated with one responding patient with refractory CD5+ DLBCL able to proceed to allogeneic transplant who remains in continuous remission. Enrollment continues to both cohorts A and B in this trial to the defined interim analysis point of 16 patients in each arm, with a requirement of 5 responses in each arm to continue the study. DisclosuresMaddocks:Pharmacyclics, Seattle Genetics, MorphoSys: Advisory Board Other, Research Funding. Cohen:Pharmacyclics: Consultancy; Seattle Genetics: Consultancy; BMS: Research Funding; Janssen: Research Funding. Christian:Immunomedics: Research Funding.