Yr Progression-free Survival Research Articles

The Burkitt Lymphoma International Prognostic Index (BL-IPI)

The Burkitt Lymphoma International Prognostic Index (BL-IPI)

Impact of Race and Geographic Location on Outcomes in Allogeneic Transplant

Impact of Race and Geographic Location on Outcomes in Allogeneic Transplant

Long-term follow-up of BMT CTN 0702 (STaMINA) of postautologous hematopoietic cell transplantation (autoHCT) strategies in the upfront treatment of multiple myeloma (MM).

8506 Background: STaMINA was a phase III trial comparing progression-free survival (PFS) among 758 pts randomized to: 1. second autoHCT then lenalidomide (Len) maintenance (Auto/Auto, n = 247); 2. consolidation with Len/bortezomib/ dexamethasone (RVD) followed by Len maintenance (Auto/RVD, 254); 3. Len maintenance (Auto/Len, 257). All three arms were similar (Stadtmauer JCO 2018). Len maintenance was designed to continue for 3 years and amended to allow continuation until disease progression through a follow up protocol (07LT, NCT#02322320). We report 6 yr follow up for STaMINA and the results of Len discontinuation beyond 3 years. Methods: 07LT was offered to pts who were progression-free at 38 mo; completed planned Len maintenance and were within 4 years of BMT CTN 0702 follow up. Among 431 07LT eligible patients, 273 enrolled and 179 opted to continue maintenance until disease progression. All patients enrolled in STaMINA were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and long-term outcomes for patients not enrolled on 07LT (N = 166) were available through this mechanism. Before combining 07LT data and CIBMTR data for LTFU analysis, outcomes in both databases were analyzed separately and confirmed to be comparable. Results: Using intent-to-treat (ITT), 6yr PFS and overall survival (OS) was the same among Auto/Auto (43.9%; 73.1%), Auto/RVD (39.7%, 74.9%) and Auto/Len (40.9%, 76.4%)(p = 0.6; p = 0.8). Protocol defined high risk disease, (HR = 1.53, p < 0.0001) and age (p = 0.03) were adverse risks for PFS. In as treated analysis, 6yr PFS were 49.4%, 39.7% and 38.6% for Auto/auto (170), Auto/RVD (222) and Auto/Len (361), respectively (p = 0.01). 6yr PFS in high risk pts as treated analysis were 43.6% and 26% for Auto/auto and Auto/Len, respectively (p = 0.03). Landmark analysis at 38 mo included 215 pts who continued Len maintenance (either on 07LT study or commercial Len) vs. 207 who stopped. Baseline demographics; study arm on 0702, induction pre-autoHCT were similar. Len discontinuation after 38 mo was associated with inferior PFS (79.5% vs. 61% at 5yr; HR = 1.91, p = 0.0004) but similar OS. Incidence of all second primary malignancies (SPM)(81 cases with 43 heme-malignancies) was associated with age. Conclusions: Long term outcomes are similar using ITT, but as treated analysis suggested a PFS benefit for tandem autoHCT, driven mainly by pts with high risk MM. Len discontinuation even at 38 mo was associated with inferior PFS. Clinical trial information: NCT02322320 .

Transoral robotic surgical resection followed by randomization to low- or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3311).

6500 Background: ECOG-ACRIN 3311 examines reduced postoperative therapy in patients with “intermediate risk” p16+ oropharynx cancer (OPC) undergoing primary transoral surgical management. We report the primary endpoint of 2-year progression free survival (PFS) for patients randomized to 50Gy vs 60Gy without chemotherapy. Methods: Between December 2013 and July 2017, 82 credentialed surgeons performed transoral resection (TOS) for 519 OPC patients (cT1-2 stage III/IV AJCC7 without matted neck nodes); post-operative management was determined by pathologically assessed risk. Among 353 eligible and treated patients, Arm A enrolled 10% (N=37) for clear margins, 0-1 nodes, no extranodal extension (ENE)), Arms B (50Gy, N=102) or C (60Gy, N=104) randomized 58%, for clear/close margins, 2-4 + nodes, or ENE ≤1mm, while Arm D (N=110, 60-66Gy plus weekly cisplatin, 40 mg/m2, positive margin with any T stage, >4 + nodes, or >1mm ENE) enrolled 31%. Arm D assignment was based on >1mm ENE (76%), > 4 nodes (27%), and/or positive margins (11%). Intermediate-risk patients were stratified by smoking history (>10 pk-yr). Of the 80 pts (15%) deemed ineligible, 28 had scans/labs not done per protocol, however treatment arm distribution for all patients mirrored that for the 353 pts eligible and treated. Results: Median follow-up was 31.8 months. 2 yr PFS for Arms A, B and C were 93.9% (90% CI=87.3%, 100%), 95.0% (90% CI=91.4%, 98.6%) and 95.9% (90% CI=92.6%, 99.3%) respectively, while Arm D was 90.5% (90% CI=85.9%, 95.3%). The regimen of TOS + low-dose radiation is considered worthy of further study, since the primary endpoint of the upper bound of the 90% CI (in the intermediate risk group) exceeding 85% was met. Of 17 progression events, 7 were locoregional. There were 10 distant recurrences: Arm A=1, Arm B=2, Arm C=4, Arm D=3. Grade III/IV treatment-related AE rates were 15%/2% during surgery, 13%/2% for Arm B and 25%/0% for Arm C. There were 2 treatment-related deaths (one surgical and one Arm D). Conclusions: Transoral resection of p16+ OPC is safe and results in good oncologic outcome, presenting a promising deintensification approach. For patients with low-risk disease, 2-yr PFS is favorable without post-operative therapy. For those with uninvolved surgical margins, <5 involved nodes, and minimal (<1mm) ENE, reduced dose postoperative RT without chemotherapy appears sufficient. Transoral surgery plus 50Gy should be compared to optimal non-surgical therapy in a phase III trial. Clinical trial information: NCT01898494 .

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS425 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a favourable response, and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in the favourable response rate and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 13 sites open in UK (led by Cambridge Clinical Trials Unit), 67 sites open in the USA (led by Children’s Oncology Group). As of September 2019, 98 patients have been recruited triggering the first formal interim analysis. Clinical trial information: NCT02582697.

Effect of obesity on response to checkpoint inhibitors in renal cell cancer.

634 Background: Response to checkpoint inhibitors (CPIs) for renal cell cancer (RCC) remains variable, with markers like PDL1 proving unreliable. Preclinical models suggest that obesity could affect CPI outcomes. We conducted a retrospective study on the effect of obesity on outcomes in RCC patients treated with CPIs. Methods: RCC patients treated with nivolumab +/- Ipilimumab at university of Alabama at Birmingham (UAB) and University of Iowa (UIOWA) from 2015 - 2018 were classified according to WHO standard definition of BMI as non-obese (NOB-<30kg/m2) or obese (OB->30Kg/m2). Overall survival (OS) was defined as the interval from the first CPI dose to date of death or to last follow up date if patients were still alive. Progression free survival (PFS) was defined as the interval from the first dose of CPI to date of progression or date of death and censored at last follow-up date if patients were still alive without progression. Multivariable Cox proportional hazard regression model was used to evaluate the association between OS/PFS and obesity status, controlling for age, sex, race and number of prior therapies. All analyses were performed using SAS 9.4. Results: 84 patients with at least 6 months follow-up received a median of 9 doses of CPI with median follow of 72 weeks. 48 patients were NOB while 36 patients were OB, with 40 patients deceased at time of analysis. The most common response was stable disease in 45%, with CR in 5% and PR in 10% for a disease control rate of 63%. The median OS was 30 months in NOB patients and 20 months in the OB group. The 2 yr survival was 59% in the NOB group vs 28 % in the OB group with a HR of 0.60 (0.32-1.14; p=0.12). Median PFS was 13 months in the NOB group vs 7.3 months in the OB group with 2 yr PFS of 28% in the NOB group vs 5.5% in the OB group (HR 0.58 {0.35-0.98}; p=0.04). Conclusions: In this analysis of RCC patients treated with CPI, BMI < 30 predicts better OS and PFS. Further studies are required to better understand the effect of BMI on CPI outcomes in RCC.[Table: see text]

Haplo-Cord Transplantation with Anti-Thymocyte Globulin: Comparative Clinical Outcomes with or without Routine G-CSF Administration

Introduction: Haplo-cord transplantation - the co-infusion of a single umbilical cord graft with CD34-selected cells from a haplo-identical donor, offers an alternative stem cell source for patients lacking HLA-matched donors. The T-cell depleted haplo-graft acts as a myeloid bridge until replaced by durable cord hematopoiesis. Anti-thymocyte globulin (ATG) is routinely used in haplo-cord preparative regimens to reduce graft failure, graft vs. host disease (GVHD) and graft vs. graft reactions. ATG depletes T-lymphocytes through Fas-mediated apoptosis, but also indirectly stimulates T-cell destruction through antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) (de Koning, Blood Adv. 2018). Excessive depletion of cord lymphocytes may compromise immune reconstitution and graft vs. tumor effects. G-CSF administration early post-transplant may sensitize cord lymphocytes to the cytotoxic effects of residual ATG. G-CSF drives myeloid precursor proliferation and activates phagocytosis, facilitating increased ADCP and ADCC of ATG-coated cells (de Koning, Blood Adv, 2018). Prior to the publication of this data, our institutional practice was to administer G-CSF to haplo-cord transplant recipients from day +6 until neutrophil engraftment. In April 2018, we altered our practice - withholding routine G-CSF treatment. We here compare our transplant outcomes 1 year before and after this practice shift. Methods: We examined consecutive adult patients with hematologic malignancy that underwent haplo-cord transplantation conditioned with fludarabine and melphalan with or without total body irradiation (400 cGy) at Weill Cornell Medicine, between 04/2017 and 04/2019. All patients received rabbit ATG (Thymoglobulin) 1.5 mg/kg on days -5, -3 and -1 (total dose 4.5 mg/kg). Data was collected as part of study 01810588 registered at clinicaltrials.gov. Probabilities of relapse, relapse-related mortality (RRM) and non-relapse mortality (NRM) were generated using cumulative incidence (CI) estimates to accommodate competing risks. Probabilities of overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates and inter-group comparison performed by log-rank testing. Variables with potential survival impact were evaluated in a Cox proportional hazards regression model. Results: The study included 59 haplo-cord recipients - 30 who received G-CSF (GCSF group) and 29 who did not (NO GCSF group). Groups were well matched for age, weight, disease, DRI, baseline lymphocyte count, CMV recipient/donor status and TBI treatment (Table). Neutrophil engraftment occurred at a median of 10 days in the GCSF group vs. 14 days in the NO GCSF group (p=0.0002), and platelet recovery at a median of 20 and 22 days (p=-0.61). Primary graft failure occurred in 1 GCSF patient and 2 NO GCSF patients (p=0.53). The incidence of acute GVHD (grade II-IV) by day 100 was 10% in both groups (p=0.97). There was no significant difference between GCSF and NO GCSF in the CIs of relapse, RRM or NRM at 1yr. No difference was found in 1yr OS or PFS on univariate analysis (Table). After adjusting for patient age, weight, lymphocyte count prior to ATG, disease subtype, CIBMTR disease risk index (DRI), Karnofsky performance status (KPS), comorbidity score and TBI exposure, in multivariate analysis, no effect on OS or PFS was observed. CMV reactivation was observed in 40% (GCSF) vs. 21% (NO GCSF) (p=0.11). The trend towards lower reactivations in the NO GCSF may in part be due to the introduction of letermovir prophylaxis for CMV positive transplant recipients in 02/2018. Acknowledging the limited follow up of NO GCSF patients, we note a trend towards improved CD4 counts at 1yr in this group - median 271 cells/μL (n=6, IQR25-75 = 240-342) vs. 155 cells/μL in the GCSF group (n=16, IQR25-75 = 111-473) (p=0.17). Conclusion: Our data shows that G-CSF can safely be eliminated from haplo-cord transplant. We see a delay in neutrophil engraftment but no adverse effect on early morbidity or mortality outcomes. We continue to withhold early G-CSF while assessing long-term outcomes. Longer follow-up is needed in our cohort to enable a systematic analysis of immune reconstitution. Early CD4+ cell recovery after ATG treatment has been shown to improve OS, PFS, NRM and RRM (Admiraal, Lancet Hem 2015 & 2017). Disclosures Van Besien: Miltenyi Biotec: Research Funding.

Bi-Institutional Analysis of Stage III/IV Diffuse Large B Cell Lymphomas (DLBCL) Patients Undergoing Consolidative Radiotherapy: Potential for Improved Overall Survival (OS) and Progression Free Survival (PFS)

Diffuse large B-cell lymphoma (DLBCL) is the most common of the aggressive non-Hodgkin’s lymphomas. Systemic therapy is considered essential, with the established regimen in the modern age consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for three to six cycles. The use of consolidative radiation therapy after chemotherapy is a topic of debate, especially for stage III/IV patients. Some institutions have treated select stage III/IV DLBCL patients, if patients presented with bulky disease, had a partial response to chemotherapy, or had skeletal involvement at initial site of presentation. The exact role of consolidative radiotherapy in stage III/IV cohort is not known. A de-identified database consisting of 287 patients across two institutions, Emory Winship Cancer Institute (Atlanta, GA) and Duke Cancer Institute (Durham, NC), treated for DLBCL was compiled. Patients were selected from this database if found to have histologically confirmed stage III-IV DLBCL at diagnosis, and determined to have achieved complete response after systemic therapy. Those that were observed were then compared with those that additionally received consolidative radiotherapy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and survival distributions were compared using log-rank tests for patients receiving systemic therapy alone versus systemic therapy combined with consolidative radiotherapy. Statistical significance was assessed at the 0.05 level, and the statistical analysis was performed using a data and decision management product. Of the 287 patients included in the database, 188 met our selection criteria. Of note, the majority of these patients were treated with R-CHOP, with a minority receiving a modified rituximab-containing regimen or no rituximab at all. Additionally, this subgroup included patients with or without bulky disease at diagnosis. Of the selected patients, 53 received consolidative radiotherapy and the remaining 135 received chemotherapy therapy alone. At the 5-year time point, consolidative radiotherapy was associated with significantly improved OS (87.4% vs. 72.9%, p=0.0134) and PFS (85.9% vs. 49.2%, p<0.0001). The addition of consolidative radiotherapy for advanced stage DLBCL patients who demonstrate complete response after chemotherapy is associated with a 14.5% absolute benefit in 5 yr OS and a 36.7% absolute benefit in 5 yr PFS, when pooling data together from two different institutions. This work provides a basis for the use of consolidative radiation therapy in patients treated for DLBCL who demonstrate complete response after systemic therapy.

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS539 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a complete response (CR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in achieving a CR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or Filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 11 sites open in UK (led by Cambridge Clinical Trials Unit), 19 sites open in the USA (led by Children’s Oncology Group). As of 23rd October 2018, 59 patients have been recruited. Clinical trial information: NCT02582697.

Seven Year Follow up and Comparison of Dosing Strategies from the Pivotal Phase II Clinical Trial of Lenalidomide Plus Rituximab (R2) in Previously Untreated Follicular Lymphoma

Introduction: We have previously reported the results of cohort A from a single arm, phase II clinical trial of lenalidomide with rituximab (R2) as frontline treatment for patients with previously untreated follicular lymphoma (FL), Fowler N et al Lancet Oncology 2014. Recent randomized studies (RELEVANCE) did not demonstrate superiority of either R2 or R-Chemo in untreated, high GELF FL, but follow up is short. We now report outcomes of an additional extended dosing cohort (12 mo of R2) and the long term follow up of the both dosing schedules in untreated FL.Methods: A total of 154 pts were included in the original clinical trial (FL, n=80; MZL, n=31; SLL, n=43). Characteristics were collected at the time of starting R2 treatment. Patients received lenalidomide 20 mg/day on days 1-21 of each 28-day cycle and rituximab 375 mg/m2 on day 1 of each cycle (6 cycles; schedule A) and lenalidomide 20 mg/day on days 1-21 of each 28-day cycle for cycles 1-6 then lenalidomide 10 mg/day on days 2-22 for cycles 7-12 with rituximab 375mg/m2 IV x1 weekly on cycle 1 and day 1 of every subsequent cycle (12 cycles; schedule B). Responders continued treatment for at least 6 but up to 12 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints were complete and partial response (CR, PR), safety, and progression free survival (PFS). PFS was defined as time from starting treatment to disease progression or death, event free survival included time from starting treatment to discontinuation due to any cause and overall survival (OS) was defined from the time of initial diagnosis of FL to death/last follow up.Results: Eighty pts with FL were enrolled in study and followed a median of 86 months. Median age was 58 years (range, 29 to 84); 50% were males. 61% pts had grade 1 FL and 39% had grade 2 FL. Schedule A was administered in 50 pts and schedule B in 30 pts. Seventy seven pts were evaluable for initial response assessment and 76 (98%) responded. The best response rate was 95% (87% CR/CRu). At the time of last follow up, 23 patients experienced disease progression, 13 lost to follow up (all had CR as best response and had completed tx), 4 came off study due to pt choice/financial and 4 due to intolerance (2 arterio-thrombotic event, 1 respiratory failure, 1 intolerance) during therapy. After a median follow up of 86 mo, 23 pts (29%) progressed, 5 yr PFS was 75%. Five yr PFS was 70% and 82% for pts on cohort A vs B respectively (P=.30). Overall, 2 pts died, with a 5 year survival 97%, Figure-1 (A-B). The median event free survival in pts with FL was 85 months with a 5 year EFS of 59%. Subgroup analysis showed no statistically significant difference in PFS with FLIPI score, bulky disease and by initial bone marrow involvement. Pts who achieved CR had significantly longer PFS compared to those who did not achieve CR (not reached vs 78 months; p = 0.004), however the OS was not significantly different between the two groups Figure-1 (C-F). Grade 3 or 4 hematologic AEs included neutropenia (28%), thrombocytopenia (3%), and no anemia. Count recovery occurred in all pts with follow up and/or dose modification. Nine pts developed second primary cancers, including one melanoma in-situ, 3 localized skin cancers, and 2 secondary hematologic malignancies.Conclusions: A combination of lenalidomide with rituximab produced durable responses in pts with FL. At a follow up of 7 years, the majority of pts remain in remission and patients who achieved CR had the best outcomes. Five year PFS may be longer in pts who received 12mo of therapy, but will need larger analysis to confirm. Further studies are ongoing to analyze mutation dynamics and genomic profile to identify molecular biomarkers. [Display omitted] DisclosuresFowler:Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Nastoupil:Novartis: Honoraria; Juno: Honoraria; Gilead: Honoraria; TG Therappeutics: Research Funding; Spectrum: Honoraria; Janssen: Research Funding; Merck: Honoraria, Research Funding; Karus: Research Funding; Genentech: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Westin:Apotex: Membership on an entity's Board of Directors or advisory committees; Celgen: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Wang:Kite Pharma: Research Funding; Novartis: Research Funding; Pharmacyclics: Honoraria, Research Funding; Dava Oncology: Honoraria; Juno: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MoreHealth: Consultancy; Acerta Pharma: Honoraria, Research Funding. Samaniego:ADC Therapeutics: Research Funding.

Five-Year Outcomes of SWOG S1106: A Randomized Phase II US Intergroup Study of R-HCVAD Vs. R-Bendamustine Followed By Autologous Stem Cell Transplant for Patients with Mantle Cell Lymphoma

Introduction: The optimal initial management of mantle cell lymphoma (MCL) is unknown, but aggressive induction chemoimmunotherapy followed by autologous stem cell transplant confers long remission durations and is standard for younger patients. Cytarabine-based induction achieves higher rates of MRD-negativity compared to anthracycline-based induction regimens and correlates with improved outcomes. Whether a similar benefit exists after bendamustine-rituximab (RB) induction is unknown. S1106 compared induction R-HyperCVAD/MTX/ARAC (RH) or RB followed by autologous stem cell transplantation (ASCT). We previously reported similar 2-year (yr) progression-free survival (PFS) and overall survival (OS) with either regimen, and provocatively found that MRD negativity was similar with both regimens. RH was more toxic than RB and had higher stem cell mobilization failure rates.Methods: Inclusion criteria were untreated stage III, IV or bulky stage II MCL, Cyclin D1 +, age > 18-65, and adequate organ function. Randomization was stratified by MIPI. Patients (pts) received either 4 cycles of RH or 6 cycles of RB followed by ASCT. MRD was assessed at baseline and post induction. Extraction of genomic tumour DNA from paraffin embedded tissue or bone marrow aspirate and PCR amplification of IGH-VDJ, IGH-DJ, and IGK regions was performed followed by high-throughput sequencing to determine the tumor clonotype(s) (Adaptive Biotechnologies). DNA from peripheral blood mononuclear cells (PBMC) and plasma was amplified and sequenced to determine lymphoma molecules per million diploid genomes. Herein we report the results of the updated analysis at a median follow-up (mFU) of 5 yrs.Results: Fifty-two of 53 pts were evaluable. Baseline characteristics were similar between the two groups except for more female pts in the RH group. This study was closed based on prespecified criteria of stem cell mobilization failures in the RH arm. With mFU of 5 yrs (range, 29 days-6yrs), updated ORR (94.1% RH vs. 85.7% RB) and CR (41% RH vs. 43% RB) rates were similar. The 5-yr estimated PFS was 62% and 66% and the 5-yr estimated OS was 74% and 80% for RH and BR, respectively (Fig.1). Increased grade 3/4 toxicity and inadequate stem cell mobilization was seen in the RH arm thus challenging its use as an induction platform for future upfront MCL trials. 9/17 pts in RH and 23/35 pts in RB arm underwent ASCT. A landmark analysis was performed evaluating 5-yr PFS and 5-yr OS with and without ASCT in each arm. (Table 1) 27 patients consented to optional MRD assessment, with 12 paired serial samples (baseline and post induction). Overall, the estimated 5 yr PFS was 90% for all patients who achieved MRD negative status at the end of RB. Long-term toxicity included acute myeloid leukemia (N=1) in the RH arm at 5.4 yrs after diagnosis and lung cancer (n=1) in the RB arm at 2.9 yrs after diagnosis.Conclusion: The optimal induction regimen prior to ASCT in the initial management of MCL is a source of significant debate. Our initial findings supported RB as an effective platform with the ability to achieve MRD negativity. Long-term results of this study continue to demonstrate excellent response rates, 5-yr PFS and 5-yr OS with either RH or RB without any new toxicity signal. The 5-yr outcomes with RB compare favorably to more aggressive cytarabine-based induction regimens. Thus, R-Bendamustine could be an excellent backbone for induction therapy in transplant eligible patients and needs to be tested in larger phase III trials.Support: NIH/NCI grants CA180888, CA180819, CA180821, CA180820, and in part by Sequenta, Inc. (Adaptive Biotechnologies) [Display omitted] DisclosuresKamdar:Seattle Genetics: Speakers Bureau; Genentech: Consultancy. Chen:Millennium Pharmaceuticals: Consultancy, Research Funding; Affimed: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Genentech Inc.: Consultancy. Rimsza:NanoString: Other: Inventor on the patent for the Lymph2Cx assay. Barr:AbbVie, Gilead: Consultancy. Phillips:Genentech: Consultancy; Seattle Genetics: Consultancy; Bayer: Consultancy; Gilead: Consultancy; Pharmacyclics: Consultancy, Research Funding; Abbvie: Research Funding. Leonard:ADC Therapeutics: Consultancy; Karyopharm: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Genentech/Roche: Consultancy; Gilead: Consultancy; Juno: Consultancy; Sutro: Consultancy; AstraZeneca: Consultancy; BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; MEI Pharma: Consultancy; United Therapeutics: Consultancy; Biotest: Consultancy. Kahl:Seattle Genetics: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Acerta: Consultancy; CTI: Consultancy; Juno: Consultancy; ADC Therapeutics: Consultancy; Genentech: Consultancy. Friedberg:Bayer: Honoraria. Smith:Portola: Honoraria; BMS: Consultancy.

Bortezomib Maintenance (BM) or Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): 8 Year Follow up of CALGB 50403 (Alliance)

Bortezomib Maintenance (BM) or Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): 8 Year Follow up of CALGB 50403 (Alliance)

Consolidative Radiation Therapy (RT) for Advanced Stage Hodgkin’s Lymphoma (HL) May Improve Progression Free Survival Than ABVD Alone for Adult Patients.

The use of RT was associated with improved 5- and 10- years overall survival, especially for early stage Hodgkin’s Lymphoma (Bates et al 2017; Master et al 2017; Odei et al 2017). However, there is no consensus for the use of RT in advanced stage Hodgkin’s disease. We sought to compare outcomes for advanced stage HL patients undergoing RT at our institution, compared with those receiving only ABVD. After receiving Institutional Review Board approval, we captured patient, tumor and treatment characteristics, along with known adverse risk factors as well as toxicity for all advanced stage HL patients treated from 2000 – 2016. Overall survival (OS), and progression-free survival (PFS) were estimated and compared between patients who received consolidative RT versus those who only received chemotherapy. Radiation therapy had to be delivered with 90 days of completing chemotherapy. Pediatric patients were omitted from this analysis. A total of 340 patients with stage III/IV Hodgkin’s Lymphoma were analyzed. Only 47 patients received RT, with only 24 receiving consolidative RT within 90 days of chemotherapy completion. The cohort which received consolidative radiation therapy (n=24) had a 1-year (yr) PFS of 90.0% [65.6, 97.4%], a 2-yr PFS of 75% [50.0%, 88.7%], and a 5-yr PFS of 64.6% [39.7%, 81.3%]. 16 of the patients in this cohort received ABVD chemotherapy, while 4 patients received Stanford V, 3 received BEOCOPP, and 1 received MOPP. As long as radiation therapy was administered at some point after the initial diagnosis (n=47), the 5-yr OS was 100%. The cohort which received ABVD chemotherapy and consolidative RT (n=13) had a 1-yr PFS of 83.9% [49.4%, 95.7%], 2-yr PFS of 58.7% [27.4%, 80.4%], and a 5-Yr PFS of 50.3% [21.2%, 73.9%]. This was further compared with a group of 161 patients who received ABVD alone. The ABVD alone group had a 1-Yr PFS of 59.6% [51.4%, 66.9%], a 2-Yr PFS of 42.5% [34.4%, 50.3%], and a 5-Yr PFS of 28.0% [20.5%, 35.9%]. The ABVD alone cohort had a 1-yr and 2-yr OS of 100% and a 5-yr OS of 96.1% [88.5%, 98.7%]. Borderline Significance was seen when comparing the PFS of the ABVD alone cohort with the ABVD and consolidative RT cohort (p=0.085). Consolidative radiation therapy may improve 1-, 2-, and 5-years progression free survival than ABVD chemotherapy alone in advanced-stage Hodgkin’s Lymphoma. Future trials should evaluate the role of consolidative RT in advanced stage HL.

P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS574 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in RR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days (D) 1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV (D 1, 8, 15 or D 2, 9, 16 of a 21 day cycle; D 1, 8 or D 2, 9 of a 14 day cycle); and peg G-CSF or Filgrastim; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 1/19 sites open in UK (led by Cambridge Clinical Trials Unit), 41 patients recruited by September 2017. International collaborations with USA (led by Children’s Oncology Group) and Ireland (led by Cancer Trials Ireland) confirmed with sites expected to open by late 2017 and more sites sought for stage 2. Clinical trial information: NCT02582697.

Abstract 3283: Adjuvant therapy associated with improved survival in gall bladder cancer: A single institution retrospective study

Abstract Introduction: The survival outcome of resected gallbladder carcinoma remains poor. We conducted a retrospective study to examine factors affecting patient outcomes in resectable gallbladder carcinoma. Methods: We retrospectively collected data on patients treated at our institution between January 2005 and June 2015 from the electronic medical record using a standardized data collection tool. The univariate Cox proportional hazard model was used for evaluating predictors of overall survival. Kaplan-Meier method was used to compare time-to-events among subgroups and the p values were calculated by the log-rank method. Overall survival (OS) was defined as the time between surgery and death, or censored at the last follow-up date. Progression-free survival (PFS) was defined as the time to recurrence or death. Results: Of 67 evaluable patients, 65.7% were female. While clinical staging determined 51% to be stage 2 or less, interval portal lymphadenectomy and hepatic resection upstaged 20% to stage 3 or 4. Adjuvant chemotherapy (CT) was given to 18% and adjuvant chemoradiation (CRT) to 15%. About 46% did not receive any post-operative treatment and data was not available in 21%. On multivariate analysis, albumin &amp;lt; 3.5g/dl, LN involvement and pathological (p)Stage &amp;gt;2 were independent predictors of OS and PFS. Median 5 yrs OS and PFS of pstage &amp;lt; 2 was 54% and 54% respectively. Median 5 yr OS and PFS of stage ≥3 was 10.9% and 5.8% respectively. Adjuvant therapy was administered commonly for stage 3 and 4 (20 patients) compared to stage 1 and 2 (2 patients). In stage ≥3, adjuvant therapy improved OS (17.5% vs 8.9% for surgery alone) and PFS (12% vs 0%). Adjuvant chemoradiation for stage 3/4 had better median OS advantage compared to chemotherapy alone (54 m vs 15m, p=0.0008). Conclusion: The use of adjuvant treatment may improve long-term disease control in patients with node positive tumors. A significant difference between CRT and CT was demonstrated in our series and needs further validation in a larger cohort. Overall survial (OS) and progression-free survival (PFS) among various subgroupsGroup (n)Median OS (months)5 year OSMedian PFS (months)5 year PFSstage 1&amp;2 (21)NA54%NA54%stage 3&amp;4 (46)13.410.9%9.45.8%Surgery + Adjuvant treatment (22)25.115.9%16.910.9%Surgery alone (31)26.134.4%21.331.8%Surgery + CRT (10)54.235%45.724%Surgery + CT (12)14.90%13.40%Stage 3 and 4- Surgery + Adjuvant treatment (20)27.317.5%22.512%Stage 3 and 4- Surgery alone (15)2.78.9%2.10% Citation Format: Lakshminarayanan Nandagopal, Martin J. Heslin, John R. Porterfield, Rojymon Jacob, Peng Li, James Posey, Ravikumar Paluri. Adjuvant therapy associated with improved survival in gall bladder cancer: A single institution retrospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3283. doi:10.1158/1538-7445.AM2017-3283

P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).

TPS4592 Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Accelerating regimens by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and paediatric age groups open to both males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open-label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in RRs and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 yrs with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT:Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF 6mg SC on Day 6; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30-day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 27 sites open in ANZ, 34 patients recruited by February 2017. International collaborations with UK (led by Cambridge Clinical Trials Unit) and US (led by Childrens Oncology Group) confirmed with sites expected to open by early 2017, and more sites sought for stage 2. Funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and previously CINSW. ANZCTR: ACTRN12613000496718. Clinical trial information: NCT02582697.

Autologous (auto) versus matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic (allo) hematopoietic cell transplantation (HCT) in follicular lymphoma (FL) patients (pts) with early chemoimmunotherapy failure (ECF): A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis.

7508 Background: Contrary to most FL, high-risk FL pts with ECF (i.e. relapse within 2 yrs of frontline chemoimmunotherapy) have a 5 yr OS of only 50%. (Casulo, JCO 2015). We used the CIBMTR database to compare autoHCT versus either MSD or MUD alloHCT as the first transplant approach in FL pts with ECF. Methods: Adult FL pts (age ≥18) undergoing autoHCT or alloHCT between 2002-2014 and receiving first line rituximab-based chemoimmunotherapies with evidence of ECF (defined as disease relapse or progression within 2 yrs of treatment initiation) were included. The primary endpoint was OS; secondary endpoints were progression-free survival (PFS), relapse and non-relapse mortality (NRM). Results: 440 pts had ECF (auto = 240, MSD = 105, MUD = 95) (Table 1). The 5 yr adjusted probabilities (AjP) of NRM were significantly lower with autoHCT (5%), versus MSD (17%) or MUD (33%) HCT (p&lt;0.0001). 5 yr AjP of relapse were significantly lower with MSD (31%) or MUD HCT (23%), versus autoHCT (58%; p&lt;0.0001). AjP of 5 yr PFS following auto, MSD and MUD HCT were 38%, 52% and 43% (p=.006) respectively. The AjP of 5 yr OS was significantly higher following autoHCT (70%) or MSD HCT (73%) versus MUD HCT (49%; p=0.004). Conclusions: AutoHCT for FL pts with ECF has low NRM and 5 yr OS rates (70%) that are provocatively higher than historical data (~50%). MSD HCT had the lowest relapse rate with similar survival. A prospective trial confirming the role of HCT in ECF FL is warranted. [Table: see text]

Impact of a pre- and postoperative chemotherapy (Ctx) on overall survival (OS) and progression free survival (PFS) in locally advanced gastric cancer (LAGC).

156 Background: Perioperative Ctx has become standard of care for LAGC. Duration of pre- and post-op Ctx is a matter of debate. Our study evaluated effects of varying durations of pre- and post-op Ctx on PFS and OS. Secondary endpoints were toxicity, reasons for cessation of Ctx and response. We compared the outcome to a group of pts receiving no perioperative Ctx as an internal control. Methods: Pts with LAGC were included in a prospective cohort trial from a single institution from 2007 to 2015. Inclusion criteria were T1-T4, N0-3, M0, AEG (n=27) or gastric cancers (n=65). Initial therapy decisions were made by an interdisciplinary tumor board for all pts. Pts received DDP/5-FU (qw d28 mod FFCD-Protocol, Ychou et al. JCO 2011) for 2 mo, and a 3rd mo of pre-op Ctx in case of non-progression after 2 mo and proceeded to Ctx after surgery for a planned total of six mo of Ctx. Results: 92 pts (53 m; 39 f pts) with a median age of 69 ys (range 33-96) were included. A total of 74 pts were recommended periop Ctx and 18 primary surgery (S). A total of 67 (91%) of the periop Ctx received pre-op Ctx (NA) of which 47 (64%) received 3 mo of pre-op Ctx, 19 (26%) two mo, 1 pt (1%) one mo, and 7 pts refused preop Ctx (9%) of which only 3 proceeded to surgery. Only 53 pts (72 %) received post-op Ctx; 25 pts (34%) received three mo, 9 pts (12 %) two mo, and another 10 pts (14 %) one mo of postop Ctx. Nine pts (13%) in the NA group and 20 pts (39%) in the post-op Ctx group had to stop Ctx due to toxicity after 1 (n=11) and &lt;2 (n=9) mo of Ctx. Only 23 pts (31%) received the planned pre- and postop Ctx of 6 mo in total. Up to 07/2016 a total of 36 deaths were observed (39%). 5 yr PFS was 49% in the group of periop Ctx vs 14% in the S group. PFS in pts receiving a total of &lt; 4 mo of Ctx was 36% vs. 61% in pts receiving 6 mo of Ctx. 3 yr OS was 19% in the S group vs 48% in the Ctx group. The OS in pts receiving &lt; 4 mo was 34% vs.43% in pts with 6 mo Ctx. A pCR after preop Ctx was observed in 2 pts, a PR in 47 pts, a SD in 12 pts, while a PD occurred in 3 pts only. Conclusions: Pre-op Ctx was considerably better tolerated than post-op Ctx and led to fewer Tx cessations. We found a better PFS for pts with &gt;4 mo of periop Ctx, as well as OS was affected by a shorter duration of periop Ctx.

Abstract P1-07-18: Breast cancer in young patients, twelve years of experience in a single institution

Abstract Breast cancer is very rare in young women and has a more aggressive biological behavior and a worse prognosis than in older premenopausal women. This study was designed to determine and evaluate the features of breast cancer in young patients less than 35 years old at the Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú. Medical records of 115 patients less than 35 years old with breast cancer, whom were diagnosed and received a kind of treatment, even surgery, chemotherapy, radiotherapy or all of them at the Instituto Nacional de Enfermedades Neoplásicas Lima-Perú, between January 2000 and December 2012, were reviewed. Triple negative breast cancer (38.3%) is the most common subtype cancer and its presentation is in a lower age compared with the others subtypes (27.1 years vs 28.5 years p: 0.047). The high histological grade was more frequent in triple negative and HER2 subtypes (80% both vs 30% and 48% for luminal A and luminal B p: 0.001). The 2 yr and 5 yr overall survival was 75.0% and 59.3% for luminal A, 71.4% and 55.1% luminal B, 67.7% and 54.9% triple negative, 58.3% and 41.7% HER2 (p: 0.434). The 2 yr progression free survival was 81.6%, 72.6%, 61.5% and 59.4% for each group respectively (p: 0.522). As conclusion, the breast cancer in 35 yr old or less women is uncommon; the triple negative subtype is more common, also in relation with high histological grade and in lower age. The overall survival and the progression free survival are worse in patients with lower age. Citation Format: Morante ZD, Pacheco C, Limón RS, Neciosup S, Gomez HL. Breast cancer in young patients, twelve years of experience in a single institution. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-18.

Interfollicular CD10 Expression and Follicular PD1 Tumor-Infiltrating Lymphocytes As Biologic Risk Factors in Patients with Previously Untreated Follicular Lymphoma Receiving Rituximab-Based Biologic Therapy: An Alliance Correlative Science Study (CALGB 50901, 50402, 50701, 50803, 50401)

Interfollicular CD10 Expression and Follicular PD1 Tumor-Infiltrating Lymphocytes As Biologic Risk Factors in Patients with Previously Untreated Follicular Lymphoma Receiving Rituximab-Based Biologic Therapy: An Alliance Correlative Science Study (CALGB 50901, 50402, 50701, 50803, 50401)