Longer PFS Research Articles

Abstract 1403: Correlations between overall survival and patient regulatory T-cell levels at initiation of Folfiri therapy in colorectal cancer

Abstract Twenty-three patients with metastatic colon or rectal carcinoma were enrolled in a first-line study of Folfiri therapy consisting of irinotecan (180 mg/m2 day 1), levo-leucovorin (200 mg/m2 day 1), 5-FU (400 mg/m2 bolus day 1 and 2400 mg/m2 continuous infusion over 48h), and bevacizumab (5 mg/kg day 1). This treatment schedule was repeated every 2 weeks. Peripheral blood samples were collected prior to the start of cycle I, and after 30 days, and assayed by 4-color flow cytometry and regulatory T-cell (Treg) suppression assay. Cytofluorometric analysis of PBMCs of the entire group of patients revealed no statistical differences between the PBMCs collected at baseline and post 30 days of therapy in terms of PBMC amount, percent of CD4+ T cells, CD8+ T cells, or Tregs, or the ratios of CD4+ T cells or CD8+ T cells vs. Tregs. Lower levels of Tregs (< 2.5% of PBMC) at baseline, i.e., prior to chemotherapy, were associated with a better PFS by log-rank analysis. The median PFS for patients with < 2.5% Tregs at baseline was 23.3 weeks, and for patients with >2.5% Tregs at baseline PFS was 10.7 weeks (p = 0.037, n = 23). Furthermore, a forward step-wise regression analysis model demonstrated that lower Tregs at baseline (regression coefficient = 0.467, p = 0.004) and the decrease in Tregs (as% of PBMC) at 30 days of chemotherapy (regression coefficient = 0.454, p = 0.006) were both independent predictors of better OS, independent of age, gender, ALP, LDH, mucinous vs. non-mucinous phenotype, serum CEA, serum 19.9, and number of metastatic sites. Of the 23 patients on study, 14 demonstrated clinical responses by RECIST criteria and nine did not. Eight of the 14 (57%) responders by RECIST criteria displayed Treg levels < 2.5% of PBMC at baseline, whereas only two of the seven (22%) non-responders demonstrated < 2.5% Tregs at baseline. In addition, nine of the responders by RECIST criteria (64%) showed a trend in the decrease of Tregs as% of PBMC at 30 days of therapy, whereas only 22% of the non-responders had a decrease in Tregs (p = 0.049, Chi2 = 3.9 with Pearson test). In conclusion, we found lower frequencies of Tregs at baseline in responders than non-responders, which was associated with longer PFS. In addition, lower Tregs at baseline and a decrease in Treg frequency after 1 month of Folfiri therapy were both independent predictors of longer OS. Citation Format: Caroline Jochems, Vittore Cereda, Romaine I. Fernando, Jacob Richards, Italia Grenga, Patrizia Ferroni, Fiorella Guadagni, Jeffrey Schlom, Mario Roselli. Correlations between overall survival and patient regulatory T-cell levels at initiation of Folfiri therapy in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1403.

The pro-inflammatory effect of obesity on high grade serous ovarian cancer

IntroductionObesity is a known generator of chronic inflammation but has an uncertain role in ovarian carcinogenesis and survival. Pro-inflammatory cytokines have previously been associated with poor outcomes. Given the established links, we sought to determine whether obesity and pro-inflammatory cytokines affect platinum sensitivity. MethodsA retrospective review was performed of patients undergoing primary debulking surgery (PDS) for high grade serous ovarian cancer (HGSC) who had available pre-operative serum. Oncologic and treatment characteristics were recorded and analyzed using SAS version 9.3. Bioplex reagent kit was used to measure serum cytokine concentrations. Results86 patients met study criteria. Most were Caucasian (88%) and non-diabetic (92%). All patients had advanced stage (III/IV) disease and received chemotherapy after PDS. In univariate analysis, lower VEGF (p=0.013) was associated with longer overall survival (OS). Low IL-8 level (p=0.053) was marginally associated with platinum resistant disease. After adjusting for covariates including residual disease and maintenance therapy, IL-8 was no longer associated with platinum sensitive status (p=0.13), VEGF remained associated with OS (low vs. high HR 0.3, 95% CI 0.1–0.8, p=0.018), and higher IL-12 was associated with longer PFS (HR 0.4, 95% CI 0.2–0.9, p=0.031). ConclusionIn HGSC, pro-inflammatory cytokines are influenced by obesity, as differing inter-cytokine correlations were observed based on BMI, possibly due to dysregulation between cytokines in the setting of obesity. Differences in survival and platinum sensitivity were not noted. Future studies are warranted to determine whether obesity may be a modifiable risk factor for poorer outcomes due to differing immune response.

Abstract 269: The role of BRCA1 and AEG1 mRNA expression in advanced non-small-cell lung cancer (NSCLC) patients (p) with EGFR activating and pretreatment T790M mutations receiving the combination of erlotinib plus bevacizumab (E+B) in the BELIEF trial

Abstract The BELIEF trial (NCT01562028) examined the efficacy of E+B for the 1st line treatment of European p with advanced NSCLC harboring exon 19 deletion or exon 21 L858R epidermal growth factor receptor (EGFR) mutations with or without pretreatment T790M. Median progression-free survival (mPFS) was 13.8 months (m) (95% CI 10.3-16.2) for the 109 p enrolled in the study. mPFS was 16m (95% CI 13.1-not estimable [NE]) and 10.4m (95% CI 9.2-15.6) for the 37 T790M(+) p and 72 T790M(-) p, respectively (P = 0.089). We have previously shown that low BRCA1 levels neutralize the negative effect of pretreatment T790M and are associated with longer PFS to erlotinib. Low astrocyte elevated gene 1 (AEG1) levels are associated with longer PFS to erlotinib. A secondary objective of the BELIEF trial was the assessment of the prognostic impact of BRCA1 and AEG1 mRNA expression in the baseline tumor tissue. We assessed the baseline mRNA expression levels of BRCA1 and AEG1 and correlated them with PFS and response in the 109 EGFR-mutant NSCLC p of the BELIEF trial. BRCA1 and AEG1 mRNA levels were estimable by quantitative-real time PCR in 46 and 61 p respectively. Expression levels were divided into two groups according to their median. No statistically significant associations were found among the expression of the two biomarkers and gender, smoking status, histology, PS or type of EGFR mutation. The association of BRCA1 and AEG1 mRNA with PFS did not differ according to T790M status (interaction P = 0.81 and 0.42, respectively). Among the T790M (+) p, those with low BRCA1 mRNA had a longer mPFS of 24.6m (95% CI: 4.9-NE) compared to 15.4 m (95% CI: 2.7-NE) for p with high BRCA1 mRNA; P = 0.63. For all and T790M (-) p, BRCA1 levels did not differentiate mPFS to E+B (low vs high BRCA1 mRNA, 11.0 m [95% CI: 6.0-NE] vs 9.5 m [95% CI: 7.2-NE]; P = 0.99 and 6.9 m [95% CI: 2.1-NE] vs 9.4 m [95% CI: 4.1-NE]; P = 0.71, respectively). Similarly, among the T790M (+) p, those with low AEG1 expression had a longer mPFS of 24.6m (95% CI: 4.9-NE) compared to 15.4 m (95% CI: 5.2-NE) for those with high AEG1 mRNA; P = 0.93. For all and T790M(-) p, AEG1 levels did not differentiate mPFS to E+B (low vs high AEG1 mRNA, 10.3 m [95% CI: 8.4-24.6] vs 15.4 m [95% CI: 6.0-33.9]; P = 0.90 and 10.3m [95% CI: 8.4-NE] vs 13.3m [95% CI: 4.7-33.9] P = 0.67). No statistically or clinically significant associations were found among BRCA1, AEG1 mRNA levels and response to E+B. The BELIEF trial reconfirms our previous findings that pretreatment EGFR T790M is present in 34% of the patients. E+B is associated with a prolonged mPFS of 24.6m for EGFR-mutant p with both pretreatment EGFR T790M and low BRCA1 mRNA expression, as observed in our previous study with erlotinib alone. Similar results were observed for AEG1 levels though the interaction was not statistically significant for either biomarker. Citation Format: Rafael Rosell, Niki Karachaliou, Ana Giménez-Capitán, Carles Codony-Servat, Oliver Gautschi, Enriqueta Felip, Alessandra Curioni-Fontecedro, Solange Peters, Santiago Ponce-Aix, Martin Früh, Miklos Pless, Sanjay Popat, Sinead Cuffe, Paolo Bidoli, Adolfo Favaretto, Roswitha Kammler, Urania Dafni, Zoi Tsourti, Miguel Angel Molina-Vila, Rolf A. Stahel. The role of BRCA1 and AEG1 mRNA expression in advanced non-small-cell lung cancer (NSCLC) patients (p) with EGFR activating and pretreatment T790M mutations receiving the combination of erlotinib plus bevacizumab (E+B) in the BELIEF trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 269.

MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance.

Mucin glycoprotein expression can be altered during the carcinogenic process. The impact on the prognosis of patients with colorectal cancer (CRC) is controversial. We analyzed tumors from 381 patients for MUC1, MUC2, MUC5AC, and MUC6 expression by immunohistochemical staining, using tissue microarrays. Progression-free and cancer-specific survival were determined using the Kaplan-Meier method. Expression of intestinal mucin MUC2 was lost in 85 (23 %) CRCs, and patients with MUC6-negative tumors showed shorter progression-free survival (PFS, p = 0.043). Gastric mucins MUC5AC and MUC6 showed high (>50 %) aberrant expression in 28 (8 %) and 9 (2 %) cases, respectively. High expression of MUC5AC was associated with longer PFS (p = 0.055). High expression of MUC6 was associated with 100 % PFS (p = 0.024) and longer cancer-specific survival (CSS, p = 0.043). MUC1 was expressed in 238 (64 %) tumors and had no impact on outcome. When analysis was restricted to stages II and III, loss of MUC2 was associated with adverse outcome. Overexpression of both MUC5AC and MUC6 significantly predicted favorable PFS and CSS. In conclusion, loss of MUC2 expression proved to be a predictor of adverse outcome, while the gain of aberrant expression of MUC5AC and particularly of MUC6 was associated with favorable outcome in CRC, notably in intermediate stages II and III.

Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the KEYNOTE-029 expansion cohort.

9506 Background: Pembro (MK-3475), an anti–PD-1 antibody that prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, is approved in several countries for treating advanced melanoma. In KEYNOTE-006, pembro showed superior OS over the anti–CTLA-4 inhibitor ipi. In a phase 3 trial, combination therapy with reduced-dose nivolumab (anti–PD-1) and standard-dose ipi showed higher ORR and longer PFS than either checkpoint inhibitor alone but was associated with increased toxicity. Preliminary data from the phase 1 KEYNOTE-029 study (NCT02089685) suggested that standard-dose pembro + reduced-dose ipi was safe and provided robust antitumor activity. Here, we present data from a larger population of patients (pts) treated with pembro + ipi in the KEYNOTE-029 expansion cohort. Methods: Eligible pts had advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy. Pts received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro 2 mg/kg Q3W until intolerable toxicity, progression, or 2 y. Response was assessed by RECIST v1.1 at wk 12, every 6 wk until wk 30, then every 12 wk thereafter. Results: Of 153 pts enrolled in the expansion, 107 had ≥18 wk of follow-up (median 6.4 mo, range 4.3-9.4) by the Oct 26, 2015, data cutoff and were eligible for analysis. 18% of pts had elevated LDH, 55% had stage M1c disease, 36% were BRAFV600mutant, 13% received ≥1 prior therapy, and 12% received a prior BRAF ± MEK inhibitor; 84% had PD-L1–positive tumors (ie, ≥1% staining in tumor and adjacent immune cells). 79 pts (74%) received all 4 ipi doses; 73 pts (68%) remained on pembro. 41 pts (38%) had ≥1 grade 3-4 drug-related AE (DRAE); 68% of these DRAEs resolved by data cutoff. DRAEs led to discontinuation of pembro and ipi in 9 pts (8%), ipi alone in 11 (10%), and pembro alone in 4 (4%); there were no treatment-related deaths. Immune-mediated AEs of any grade and grade 3-4 severity occurred in 57 (53%) and 21 (20%) pts. ORR by investigator review was 57%, with 5 (5%) CR and 56 (52%) PR; by central review, ORR was 51%, with 9% CR and 42% PR. Conclusions: Pembro 2 mg/kg in combination with 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.

Association of activated BCR and PI3K pathways with responses and longer PFS to single-agent copanlisib in heavily pretreated patients with indolent and aggressive NHL.

e19063Background: Copanlisib, a novel pan-class I PI3K inhibitor with predominant activity against α and δ isoforms, has shown promising single agent anti-tumor activity in a phase 2 study in heavi...

Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience.

By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next-generation sequencing (NGS) results were evaluated. Outcomes for patients who received a "matched" versus "unmatched" therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a "matched" therapy, 93 (26.8%) with an "unmatched" therapy. More patients in the matched group achieved stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR), 34.5% vs. 16.1%, (P ≤ 0.020 multivariable or propensity score methods). Matched patients had a longer median progression-free survival (PFS; 4.0 vs. 3.0 months, P = 0.039 in the Cox regression model). In analysis using PFS1 (PFS on the prior line of therapy) as a comparator to PFS after NGS, as expected, the unmatched group demonstrated a PFS2 significantly shorter than PFS1 (P = 0.009); however, this shortening was not observed in the matched patients (P = 0.595). Furthermore, 45.3% of the matched patients (24/53) had a PFS2/PFS1 ratio ≥1.3 compared with 19.3% of patients (11/57) in the unmatched group (P = 0.004 univariable and P ≥ 0.057 in multivariable/propensity score analysis). Patients with a "matching-score" (the number of matched drugs divided by the number of aberrations; unmatched patients had a score of zero) > 0.2 had a median overall survival (OS) of 15.7 months compared with 10.6 months when their matching-score was ≤ 0.2, (P = 0.040 in the Cox regression model). Matched versus unmatched patients had higher rates of SD ≥ 6 months/PR/CR and longer PFS, and improvement in OS correlated with a higher matching score in multivariable analysis. Mol Cancer Ther; 15(4); 743-52. ©2016 AACR.

Outcome of chemotherapy in advanced synovial sarcoma patients: Review of 15 clinical trials from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group; setting a new landmark for studies in this entity

IntroductionPrevious studies in metastatic soft tissue sarcomas (STS) showed that synovial sarcomas tend to have better survival rates and a higher chemosensitivity than other STS subtypes. However, data are derived from relatively small subgroups and statistical significance of these observations is lacking. Larger cohorts are necessary to define and confirm the specific characteristics of this subtype. Patients and methodsPatient data were retrieved from 15 European Organisation for Research and Treatment of Cancer advanced first-line STS trials. Patient characteristics, survival and treatment response of synovial sarcoma patients were compared to other STS patients. Univariable and multivariable analyses were performed to evaluate prognostic factors. ResultsIn total, 3330 advanced STS patients were retrieved, of whom 313 had a synovial sarcoma. Synovial sarcoma patients were significantly younger (median 40 versus 52 years), more often had extremity primary tumours and had a better performance status (PS 0: 50.2 versus 43.4%) compared to other STS patients. Additionally, synovial sarcoma patients had a significantly better response to chemotherapy (responders: 27.8 versus 18.8%) and better survival rates (progression free survival [PFS]: 6.3 versus 3.7 months; Overall survival [OS]: 15.0 versus 11.7 months). Age, PS, and presence of metastatic disease were defined as prognostic factors for PFS and OS in the univariable analysis. The last two factors were confirmed in the multivariable analysis for OS. DiscussionAdvanced synovial sarcomas are a distinct subgroup of STS, with a better response to systemic chemotherapy and longer PFS and OS. These results should be taken into account in the design of future synovial sarcoma specific studies.

Abstract P4-04-18: High serum miR-19a levels correlated with favorable prognosis in patients with metastatic HER2+ breast cancer and might result from effective antibody-dependent cell-mediated cytotoxicity (ADCC) induced by trastuzumab and Th1-mediated antitumor immune response

Abstract Introduction HER2 amplification is found in up to 20% of breast cancer and is associated with poor survival. To date, no predictive biomarker has been validated for clinical practice in patients with HER2+ breast cancer. Type 1 T helper lymphocytes (Th1) are required to activate antitumor cytotoxic T lymphocytes (CTL) necessary for tumor clearance. Particularly, IFN-γ secreted by Th1 cells is necessary for the development of CTL-mediated antitumor response. Trastuzumab can induce antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by natural killer (NK) cells. In turn, trastuzumab-activated NK cells can trigger Th1 cells by driving their differentiation and maturation. Furthermore, NK-mediated ADCC can increase tumor cell membrane permeability through pore formation induced by perforin secreted by NK cells. We found that: 1) high serum miR-19a levels in patients with metastatic HER2+ breast cancer were predictive of favorable prognosis; 2) Th1 cells expressed and secreted high miR-19a levels; 3) and breast cancer tissue expressed higher miR-19a levels than normal adjacent tissue. Therefore, the high serum miR-19a levels in patients with good prognosis may derive from tumor cells killed by NK-mediated ADCC and secretion from Th1 cells. MiR-19a may represent a marker of effective anti-tumor immune response. Results HER2+ metastatic breast cancer patients with high serum miR-19a levels (n=27) had longer PFS (7.9 vs. 4.1 months; p=0.003) and OS (median not reached vs. 13.1 months; p<0.0001) than patients with low serum miR-19a levels (n=24). Locally advanced breast cancer tissue (n=35) expressed higher levels of miR-19a than normal adjacent tissue (n=10) (p=0.048). KPL-4 cells (HER2-amplified) expressed higher miR-19a levels than SKBR3 cells (HER2-amplified) (p=0.010) and MCF-7 cells (non-HER2-amplified, used as control) (p<0.0001). In in vitro ADCC assay, trastuzumab induced an increased tumor cell killing by NK cells and consequent miR-19a release into the supernatants of MCF-7 (p=0.004; p=0.0005), SKBR3 (p=0.001; p<0.0001) and KPL-4 (p=0.0005; p<0.0001), respectively. Th1 cells expressed (p<0.0001) and secreted (p=0.0002) higher miR-19a levels than Th2 cells (Th1 antagonist). Patients with favorable prognosis had higher levels of IFN-γ-secreting Th1 cells (p=0.049) in the peripheral blood than patients with worse prognosis. Conclusion High serum miR-19a levels in patients with metastatic HER2+ breast cancer may result from an increased ability of trastuzumab to induce an effective NK-mediated ADCC and activation of Th1-mediated immune response. This may explain the different clinical outcome between patients with high and low serum miR-19a levels. Our results suggest that miR-19a may potentially represent a novel serum biomarker to evaluate trastuzumab response and Th1-mediated anti-tumor immunity in patients with metastatic HER2+ breast cancer. Citation Format: Anfossi S, Huo L, Woodward WA, Ueno NT, Valero V, Calin GA, Reuben JM. High serum miR-19a levels correlated with favorable prognosis in patients with metastatic HER2+ breast cancer and might result from effective antibody-dependent cell-mediated cytotoxicity (ADCC) induced by trastuzumab and Th1-mediated antitumor immune response. [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 P4-04-18.

Angiogenic markers during bevacizumab-based treatment in metastatic renal cell carcinoma (RCC).

522 Background: Targeting the vascular endothelial growth factor (VEGF) pathway delays progression in mRCC, however innate and acquired resistance limit success. CD105 (endoglin) is a TGFb family receptor which is upregulated after VEGF inhibition, possibly mediating resistance. We studied serum CD105 and TGFb at baseline and after treatment, and tissue levels of TGFbR1 & 2 plus AVCRL, to discover biomarkers for treatment response as part of a randomized trial of bevacizumab (Bev) +/- the anti-endoglin antibody TRC105. Clinical data from the trial were presented at ASCO 2015 (Dorff et al, abstr 4542). Methods: Serum was collected at baseline and before cycles 2&4. ELISA was performed using kits from Abcam. Changes from baseline were evaluated and compared overall and between arms using a general linear mixed effects model. Immunohistochemistry was performed on paraffin embedded tissue samples using antibodies from R&D systems; tissue and baseline ELISA data were evaluated for association with PFS using Kaplan-Meier analysis and the logrank test. Results: 54 subjects (24 on Bev and 28 on Bev+TRC105) had at least one analyzed serum sample; 14 and 19 respectively had both baseline and cycle 2 samples. Mean CD105 was 82.8 (95%CI 64.6, 106.2) at baseline and 59.0 (95%CI 43.2, 80.7) at cycle 2; for 16 patients with cycle 4 data the mean was 39.8, significantly lower than baseline (p = 0.024), but not different between treatment arms. Cycle 2 TGFb levels were not different from baseline (p = 0.66) or between arms (p = 0.17). Baseline serum TGFb below the median ( < 10.6) was associated with higher likelihood of PFS at 12 and 24 weeks; (0.78 vs 0.3 and 0.49 vs 0.19, respectively, p = 0.022); baseline CD105 was not (p = 0.83). Tissue was available for 29 subjects. No tissue markers (TGFbR1 &2 or AVCRL) were associated with longer PFS except, in exploratory analysis, higher TGFbR2 staining in patients treated with TRC105 (p = 0.017). Conclusions: No pharmacodynamics markers for TRC105 therapy were identified. Lower baseline serum TGFb levels may be prognostic of PFS during Bev therapy, supporting the notion that this pathway contributes to resistance. Better PFS in TRC105-treated patients with higher tissue TGFbR2 expression warrants further study. Clinical trial information: NCT01727089.

Very early PSA response to abiraterone in mCRPC patients: A novel prognostic factor to predict overall survival.

219 Background: In the last years the therapeutic scenario of mCRPC has undergone a radical change with the approval of new drugs. AA is approved for the treatment of mCRPC after failure of ADT in whom chemotherapy (CT) is not yet clinically indicated and for treatment of mCRPC progressed on or after docetaxel (DTX) based chemotherapy. The aim of this study is to evaluate the role of early PSA decline as a marker of response for an early detection of therapy success in mCRPC patients treated with AA. Methods: We retrospectively evaluated 87 pts with mCRPC treated with AA in compassionate use in Napoli, Trento, and Candiolo, Italy. Serum PSA levels were performed after 15, 90 days and then monthly, a time course of serum PSA was obtained. The PSA flare phenomenon was evaluated, according to a confirmation value at least one week apart. The Cox proportional hazards model was used to test the effect of several variables on survival outcomes in multivariate analyses. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014; 75/87 were eligible for correlation analysis. PSA decline was observed in 78.6 % (59/75) of pts. Early PSA response ( ≥ 50% from baseline at 15 days) was found in 56%(42/75) evaluated patients and confirmed in 29 of them after 90 days. In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28,95% CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The median OS was 17,1 months(8,8-25,2). PFS at 1 year and OS reached statistical significance also in the evaluation at 90 days, HR: 0.23 95% CI 0.07-0.77, p = 0.02 and HR: 0.14 95% CI 0.03-0.70, p = 0.02 respectively. Our analysis showed a positive correlation between OS and duration of AA treatment, previous chemotherapy treatment, cumulative dose of docetaxel ≤ 675 mg/m² and previous hormonal therapy duration ( ≥ 2.5 months) for metastatic setting in early responders group. Conclusions: A significant proportion (78.6%) of patients achieved a rapid response in terms of decline of PSA. Early PSA RR ( ≥ 50% at 15 days after start of AA) can provide clinically meaningful information and could be considered a surrogate of longer PFS and OS.

Abstract A032: Immunotherapy with ch14.18/CHO in combination with IL2 is active and effective in high-risk relapsed/refractory neuroblastoma patients

Abstract Background: Ganglioside GD2 is a glycolipid highly expressed on neuro-ectodermal tumors including melanoma and neuroblastoma (NB). It is ranked on position 12 of the list of tumor associated antigens by the NCI. Anti-GD2 antibody (Ab) ch14.18/CHO targets this antigen and effectively orchestrates innate immune effector mechanisms against GD2 expressing malignancies. However, one on target effect of anti-GD2 Abs is the induction of neuropathic pain when applied as short term infusion (STI) requiring co-medication with intravenous morphine. Here we investigated whether long-term infusion (LTI) of anti-GD2 Ab ch14.18/CHO may have an improved pain toxicity profile and at the same time mediate an effective immune response in patients (pts) with high risk relapsed/refractory NB which translates to objective clinical responses and an improved survival. Methods: 97 pts received 6x106 IU/m2 sc IL2 (d1-5; 8-12), LTI of 100 mg/m2 ch14.18/CHO (d8-17) and 160 mg/m2 oral 13-cis-RA (d19-32) in an ongoing SIOPEN Phase II study (APN311-202) (NCT01701479) (44 pts) and a closed single center program (53 pts) (APN311-303). Response assessments followed INRG criteria. Serum ch14.18/CHO concentration-time curves were determined by validated ELISA methods and pharmacokinetics parameter were analyzed using standard non-compartmental methods. Fcγ;-receptor polymorphisms FCGR2A (H131R), -3A (V158F) and -3B (NA1/NA2) and patient-specific antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and whole blood cytotoxicity (WBT) responses were determined. Results: LTI was associated with low pain scores and a decreasing morphine usage compared to STI. Clinical overall responses were 30% (APN311-303) and 31% (APN311-202). The survival update of the APN311-303 cohort revealed a 1-y & 4-y OS of 94.2±3.2% & 60.9±9.0% (median FU 2.9y [0.7-5.2y]) and a 1-y & 4-y PFS of 54.4±6.9% & 32.3%±6.9% (median FU 2.8y [0.7 - 4.9y]). Median TTP was 571d (95% CI: 232.7d). The comparator is the reported historical gold standard for relapsed refractory NB patients with 1-y & 4-y PFS of 19±2% & 8±3% and OS of 56±3% & 14±4% and a median TTP of 63 d (95% CI: 56.8d). NB pts with high affinity FCGR alleles and an increase in ADCC (cut off 15%) are associated with longer PFS and OS rates (p<0.03; p<0.005), supporting NK-cell mediated ADCC as the mechanism of action. Parameters of immune modulation (CDC, and WBT) and PK of ch14.18/CHO were comparable between APN311-202 and -303 cohorts. PK of ch14.18/CHO was analyzed in cycle 1: Cmax=12.2±0.4μg/ml, t½=8.4±1.1 d, AUC=145.3± 5.8 μg*d/ml, Vdss=9.3±0.5L/m2. A pro-inflammatory cytokine response (IL-2, IL-6, IL-8, IFNγ) translated into the expansion of effector NK- (3x) and T-cells (2x). We observed HACA in 17/97 pts (17.5%) of which only 9/97 (9.3%) were neutralizing with respect to the inhibition of CDC and WBT activity. In HACA negative patients, levels of ch14.18/CHO and functional parameters (CDC and WBT) analyzed before subsequent treatment cycles indicate persistent anti-NB activity for the entire treatment period. Conclusion: LTI of ch14.18/CHO has an improved pain toxicity profile and at the same time is active and effective in high-risk relapsed/refractory NB. Citation Format: Holger N. Lode, Dominique Valteau-Couanet, Alberto Garaventa, Juliet Gray, Victoria Castel, Isaac Yaniv, Nikolai Siebert, Christian Jensen, Stefanie Endres, Lena Pill, Christin Eger, Diana Seidel, Madlen Jüttner, Silke Kietz, Karoline Ehlert, Evelyne Janzek, Carla Manzitti, Ina Müller, Hans Loibner, Ruth Ladenstein. Immunotherapy with ch14.18/CHO in combination with IL2 is active and effective in high-risk relapsed/refractory neuroblastoma patients. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A032.

Improvement of Quality of Response with Ibrutinib Plus Bendamustine/Rituximab Vs Placebo Plus Bendamustine/Rituximab for Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Introduction Recent results from the HELIOS phase 3 study in relapsed/refractory CLL/SLL demonstrated that the addition of ibrutinib to chemoimmunotherapy with bendamustine/rituximab (BR) leads to an 80% reduction in risk of progression or death compared with placebo + BR (Chanan-Khan et al. ASCO 2015). In addition to prolongation of progression-free survival (PFS; median not reached vs 13.3 months; hazard ratio: 0.203, 95% confidence interval: 0.150-0.276, p Methods In total, 578 patients (pts) with relapsed/refractory CLL/SLL requiring treatment were randomized 1:1 (289 per arm) to receive BR (≤ 6 cycles) with either ibrutinib (420 mg daily) or placebo. Purine analog refractoriness (yes vs no) and number of prior therapies (1 vs > 1) were stratification factors. Pts with deletion 17p (del17p; > 20% of cells) were excluded. All pts were required to have ≥ 1 abnormal lymph node (LN; defined as a measurable lesion > 1.5 cm). The primary end point was independent review committee (IRC)-assessed PFS. In this analysis, individual parameters of response (LN, spleen, overall radiology, absolute lymphocyte count [ALC], complete blood count [CBC], and bone marrow [BM]) were evaluated. Minimal residual disease (MRD) was assessed by flow cytometry using an 8-color panel (Rawstron AC, et al. Leukemia. 2007;21:956-964); MRD samples were collected at confirmation of suspected CR (bone marrow) and every 3 months thereafter (peripheral blood). Rate of MRD-negative response was defined as the proportion of pts who reached negative disease status ( Results The ORR assessed by the IRC was 82.7% with ibrutinib + BR vs 67.8% with placebo + BR (p At baseline, similar proportions of pts in each arm had bulky disease defined as LN > 5 cm (54%-58%) or abnormal spleen (~40%) as assessed by IRC. Complete resolution of previous CLL/SLL manifestations as assessed by the IRC was achieved more often in the ibrutinib + BR arm in comparison with placebo + BR for LN (34.6% vs 15.2%), spleen (56.7% vs 37.0%), overall radiology (21.1% vs 9.0%), and BM (19.7% vs 5.9%). Rates of normalization of ALC (> 90%) and CBC (> 70%) were high and similar in the 2 arms. MRD was assessed in 120 pts treated with ibrutinib + BR and 57 pts treated with placebo + BR and was negative in 37 pts and 14 pts, respectively, which corresponds with an MRD-negative response rate of 12.8% vs 4.8% for ibrutinib + BR vs placebo + BR (p = 0.0011). Investigator-determined responses by different levels of MRD are shown in Table 1. The percentage of pts with an MRD level Conclusions Pts treated with ibrutinib + BR showed not only a higher ORR, but also a greater depth of response, with more CRs and a higher rate of resolution of LN, spleen, and BM involvement. Furthermore, the rate and depth of MRD negativity was improved, and appeared to last longer in pts treated with ibrutinib + BR compared with pts receiving placebo + BR. With a median follow up of 17 months in the ibrutinib + BR arm, no MRD-negative pts and few MRD-positive pts had progressed, thus evaluating a trend in PFS with MRD negativity is currently limited in this arm. Disclosures Cramer:Gilead: Other: Travel grant, Research Funding; Glaxo Smith Klein/Novartis: Research Funding; Astellas: Other: Travel grant; Mundipharma: Other: Travel grant; Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau. Off Label Use: Combination of bendamustine, obinutuzumab and ibrutinib for treatment of CLL. Fraser:Hoffman LaRoche: Consultancy, Honoraria; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Demirkan:Amgen: Consultancy; Celgene: Other: Travel reimbursement. Santucci Silva:Merck: Research Funding; Celgene: Research Funding; GSK: Research Funding; Janssen: Other: Travel reimbursement, Research Funding; Hoffman LaRoche: Other: Travel reimbursement, Research Funding; Novartis: Other: Travel reimbursement. Janssens:Mundipharma: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy. Goy:Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Mayer:Janssen: Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Bartlett:Millenium: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Gilead: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celgene: Research Funding. Rule:Roche: Consultancy, Other: Travel reimbursement; JJ Celgene: Consultancy, Other: Travel reimbursement; Gilead: Research Funding. Sun:Janssen/JJ Janssen: Employment, Equity Ownership. Howes:Janssen/JJ Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding.

Impact of Cytogenetics on Outcomes of Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Continuous Lenalidomide Plus Low-Dose Dexamethasone in the First (MM-020) Trial

Impact of Cytogenetics on Outcomes of Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Continuous Lenalidomide Plus Low-Dose Dexamethasone in the First (MM-020) Trial

NIMG-28TREATMENT RESPONSE EVALUATION USING FET PET COMPARED TO STANDARD MRI IN GLIOBLASTOMA PATIENTS AT FIRST RECURRENCE TREATED WITH BEVACIZUMAB PLUS LOMUSTINE

BACKGROUND: We compared prospectively MRI response assessment based on RANO criteria with metabolic O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET response evaluation during bevacizumab plus lomustine (BEV/LOM) treatment in glioblastoma patients at first recurrence. METHODS: Patients at first recurrence of a primary glioblastoma after radiotherapy with concomitant and adjuvant temozolomide chemotherapy were treated accordingly to the BELOB trial with LOM 90 mg/m2 every 6 weeks and BEV 10 mg/kg every 2 weeks. Dynamic FET PET and standard MRI scans were performed at baseline and after 8-10 weeks. FET PET metabolic tumor volumes (MTV), maximum and mean tumor/brain ratios (TBRmax/mean) as well as dynamic FET PET parameters were obtained. The predictive ability of FET PET parameters and standard MRI on treatment response assessment was evaluated with regard to PFS and OS after starting of treatment. Using receiver-operating characteristic curve analyses, threshold values for FET PET parameter changes were obtained. MRI changes consistent with “Stable Disease”, “Partial Response” and “Complete Response” were considered as treatment response. Subsequently, Kaplan-Meier survival analyses were performed to assess their predictive power for survival. RESULTS: Nineteen patients were included. Fifteen of 19 patients (age range, 34-75 years; MGMT promoter not methylated, 87%; IDH wild type, 100%) were eligible for data evaluation. Treatment response as assessed by standard MRI based on RANO criteria was not predictive for a significant longer PFS (P = 0.23) and OS (P = 0.07), respectively. In contrast, FET PET changes predicted a longer PFS (MTV decrease > 25%, P = 0.01; TBRmax decrease > 12%, P = 0.02) and OS (MTV decrease > 10%, P = 0.04), respectively. Interestingly, absolute MTV at the first follow-up scan provides the most significant prediction for increased PFS (P = 0.006) as well as OS (P = 0.003). However, both TBRmean and dynamic FET PET parameters were not predictive for treatment response. CONCLUSIONS: FET PET appears to be helpful to identify treatment responders to BEV/LOM early after initiation of treatment.

ATCT-09IDH1 R132H MUTATIONS IN NRG ONCOLOGY/RTOG 9802: PHASE III STUDY OF RADIATION THERAPY (RT) ALONE VS RT PLUS PROCARBAZINE, CCNU, AND VINCRISTINE (PCV) IN PATIENTS WITH LOW GRADE GLIOMA (LGG)

BACKGROUND: RT/PCV produces longer progression-free (PFS) and overall survival (OS) in LGG patients versus RT alone. Molecular markers have not been reported previously. METHODS: 251 eligible LGG patients were randomized to receive RT or RT/PCV. Immunohistochemistry, performed with the monoclonal antibody against IDH1 R132H, was scored positive when tumor cells showed cytoplasmic staining. Wilcoxon tests were performed to assess PFS and OS for IDH1-R132H positive vs negative patients, and, for IDH1-R132H mutated patients, for differences by treatment arm. RESULTS: Tissue suitable for IDH-R132H immunohistochemistry was interpretable for 113 (57/126 [45%] and 56/125 [45%]) patients in the RT vs RT/PCV arms, respectively. IDH1-R132H mutations were detected in 35/57 (61.4%) and 36/56 (64.3%) in the RT and RT/PCV arms, respectively, and in 77.6%, 53.8% and 48.0% of patients with oligodendroglioma, oligoastrocytoma, and astrocytoma, respectively. For patients without vs with IDH1-R132H mutations: median PFS was 1.5 vs 7.6 years (p < 0.001); and OS was 5.1 vs 13.1 years, respectively (p = 0.002). For patients with IDH1-R132H mutations: median, 5-year, and 10-year PFS were 4.7 years, 43%, and 21% in the RT arm, vs not reached (NR) (7.6+ years), 75%, and 64% with RT /PCV, respectively (p = 0.003). For patients with IDH1-R132H mutations: median, 5-year, and 10-year OS were 10.1 years, 69%, and 53% with RT, and NR (11.3+ years), 83%, and 75% with RT + PCV (p = 0.04). Tissue sufficient for determination of other genetic alterations was available in only 25% of patients, so reliable assessment is not feasible. CONCLUSIONS: IDH1-R132H mutations are associated with prolonged PFS and OS, regardless of treatment. In patients with IDH1-R132H mutations, RT + PCV is associated with longer PFS and OS compared with RT alone. SUPPORT: This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the National Cancer Institute (NCI).

RTRB-02EFFECTIVENESS OF MULTIPLE FRACTIONS GAMMA KNIFE THERAPY FOR RECURRENT MALIGNANT ASTROCYTIC TUMORS WITHOUT BEVACIZUMAB

INTRODUCTION: As temozolomide (TMZ) therapy has now become standard therapy for malignant glioma (MG), patients surviving for the long term have increased. However, use of gamma knife as second-line therapy for recurrent MG cases is not always effective. We therefore compared single- and multiple-fraction groups to clarify survival and outcomes for patients with recurrent MG. MATERIAL AND METHODS: A total of 16 consecutive cases of recurrent MG were given Gamma Knife therapy between April 2010 and September 2014 without bevacizumab, including 12 cases of glioblastoma, 1 case of anaplastic astrocytoma, and 3 cases of anaplastic oligoastrocytoma. Seven cases (total number, 8 cases) were single-fraction cases and 9 cases (total number, 13 cases) were multiple-fraction cases. RESULTS: The single-fraction group was given a 50% marginal dose of 21–24 Gy to a total of 15 lesions. The multiple-fraction group was given a 50% marginal dose of 7.5–14.5 Gy in two or three fractions, to a total of 36 lesions. Mean number of lesions treated, M-PFS, M-OS, and tumor control rate (CR, PR, SD) were 1.9, 2.3 months, 7.6 months, and 25% in the single-fraction group, and 2.8, 3.4 months, 10.0 months, and 67.2% in the in the multiple-fraction group, respectively. CONCLUSIONS: Although no significant differences in PFS, OS, or tumor control rate were evident between single- and multiple-fraction groups, the multiple-fraction group tended to show longer PFS and OS and better control rate compared to the single-fraction group.

Therapeutic effect and prognostic factors for patients with mucoepidermoid carcinoma of parotid gland

Objective To study the therapeutic effect of adjuvant chemotherapy and radiotherapy after operation in patients with mucoepidermoid carcinoma of parotid gland, and to screen the indicators ralated to the prognosis of tumor. Methods Eighty patients with mucoepidermoid carcinoma of parotid gland in First People′ Hospital of Yibin of Sichuan Province from January 2005 to December 2009 were analysed retrospectively in our research. We studied the survival of patients who were treated wtih simple operation(30 cases) or postoperative adjuvant therapy(50 cases). Then we further analyzed the relationships between the prognosis of the patients and some variables (age, gender, smoking, alcohol drinking, lymph node metastasis, distant organ metastasis, treatment method, differentiation degree and T grading). Results Kaplan-Meier survival curves showed that patients with postoperative adjuvant therapy had longer PFS and OS than those without adjuvant therapy (94.4 months vs 69.3 months; 114.9 months vs 96.7 months), with statistical significance (χ2=11.246, P=0.001; χ2=15.803, P=0.001). COX univariate analysis showed that gender (χ2=22.346, P=0.000), smoking (χ2=7.891, P=0.041), lymph node metastasis (χ2=12.371, P=0.005), distant organ metastasis (χ2=9.813, P=0.002), treatment method (χ2=25.261, P=0.000), differentiation degree (χ2=4.361, P=0.006) and T grading (χ2=5.336, P=0.014) were related to the PFS of patients. COX multivariate analysis showed that lymph node metastasis (χ2=11.003, RR=2.827, 95%CI: 1.965-3.851, P=0.011), distant organ metastasis (χ2=7.611, RR=0.472, 95%CI: 0.240-0.775, P=0.016), treatment method (χ2=24.542, RR=5.390, 95%CI: 3.585-9.602, P=0.000), degree of differentiation (χ2=3.221, RR=2.118, 95%CI: 1.845-4.719, P=0.009) and T grading (χ2=4.336, RR=0.804, 95%CI: 0.681-0.916, P=0.024) were related to the PFS of patients. COX univariate analysis showed that smoking (χ2=4.551, P=0.008), alcohol drinking (χ2=11.742, P=0.048), lymph node metastasis (χ2=14.886, P=0.009), distant organ metastasis (χ2=6.713, P=0.005), treatment method (χ2=22.411, P=0.000), degree of differentiation (χ2=8.116, P=0.012) and T grading (χ2=14.443, P=0.035) were related to the OS of patients. COX multivariate analysis showed that lymph node metastasis (χ2=11.711, RR=2.985, 95%CI: 1.521-3.999, P=0.005), distant organ metastasis (χ2=5.390, RR=0.400, 95%CI: 0.201-0.793, P=0.009), treatment method (χ2=19.327, RR=5.086, 95%CI: 3.241-8.006, P=0.000), degree of differentiation (χ2=7.084, RR=2.301, 95%CI: 1.908-4.503, P=0.001) and T grading (χ2=13.229, RR=0.561, 95%CI: 0.348-0.867, P=0.040) were related to the OS of patients. Conclusion Adjuvant radiation and chemotherapy can obviously prolong the PFS and OS for the patients with mucoepidermoid carcinoma of parotid gland. Lymph node metastasis, distant organ metastasis, treatment method, differentiation degree and T grading can greatly influence the prognosis of patients with mucoepidermoid carcinoma of parotid gland, which can be used as independent prognostic indicators for the patients with mucoepidermoid carcinoma of parotid gland. Key words: Mucoepidermoid tumor; Treatment outcome; Prognosis

Chemotherapy of metastatic triple negative breast cancer: Experience of using platinum-based chemotherapy.

The results of recent studies investigating the role of platinum-based chemotherapy (PBCT) in metastatic triple-negative breast cancer (mTNBC) were conflicting. We retrospectively investigated a large cohort (n = 379) of mTNBC to re-evaluate the role of platinums. Longer PFS was found in patients with PBCT than those with non-PBCT (7.8 vs. 4.9 months, P < 0.001) as first-line chemotherapy, but no statistical difference of OS was observed. Compared with other kinds of platinum, cisplatin-based regimens as the first-line chemotherapy showed better PFS (8.0 vs. 4.3 months, P = 0.03) and better ORR. Introduction of ≥2 lines, rather than 1 line, of PBCT can result in better OS when compared with no introduction of PBCT during the whole treatment. If considering the timing of intervention of PBCT, first-line introduction and later line introduction of PBCT did not make any difference in OS among patients with only one line PBCT during the whole treatment. We concluded that PBCT with only 1 line during the whole treatment might not be necessary for unselected mTNBC with the exception of an urgent demand to control disease or symptoms, however, ≥2 lines of PBCT did prolong OS.

Outcome of Pomalidomide Therapy in Relapsed /Refractory Myeloma: A Uk Multi-Centre Experience

e288 (Mel) a further ASCT seems reasonable. Querying effectivity and efficiency to overcome therapy-induced exhausted bone marrow function in a heavily pre-treated population, we assessed the outcomes of 61 pts. receiving a 3rd Mel-based salvage ASCT (ASCT3) after tandem ASCT as part of 1st line therapy, querying the databases of six German MM centres. 61 pts. with a median age of 63 years at ASCT3 (range, 38-77) were identified. In 5 of 50 available analyses, cytogenetics could be classified high-risk (17p13 del, t(4;14), t(14;16), amp1q21, del1p). At a median nr. of 3 lines of pre-treatment (range, 1-10) 45 pts. had either received bortezomib and/or lenalidomide, and 37 pts. both. 11 pts. had been double refractory and 23 pts. at least had been refractory to one novel agent prior to ASCT3. With a median Mel dose of 100mg/m2 and 3.1x10E6 CD34 cells/kg all pts. achieved stable engraftment despite a median graft age of 52 mos. (range, 1-154). A remarkable improvement of platelet count and haemoglobin (62.3% /49.2% of all pts.) within 3 mos. of ASCT3 could be obtained. Overall response rate ( PR) was 59% with a median PFS of 9 mos. and a median OS of 26 mos. for the entire group, respectively. 3rd salvage ASCT at late relapse is not only effective with an ORR of 59% and associated with a 9 mos.’ PFS interval but also contributes to improved haematopoiesis. Thus, pts. may tolerate further lines of therapy what is suggested by an OS of 26 mos. In addition, ASCT offers a substantial treatment-free interval when compared to either novel drug. Unfavourable cytogenetics were associated with worse PFS of 2 mos. but not median OS (8 mos.), meanwhile being double refractory was linked with an inferior OS compared to non-refractory pts. (8 vs. 23 mos.). However, benefit seems to depend on PFS after initial ASCT ( 18 mos. ->5 mos.’ PFS after ASCT3, 19-36 mos. ->18 mos., >36 mos. ->23 mos.). Figure 1 A) Progression-free survival and B) overall survival of all patients PO-359 Outcome of Pomalidomide Therapy in Relapsed /Refractory Myeloma: A Uk Multi-Centre Experience N. Maciocia, F. Sharpley, E. Belsham, H. Renshaw, S. Schey, S. Cheesman, A. Cerner, A. Rismani, S. D’sa, M. Streetly, B. Reuben, M. Jenner, K. Ramasamy, K. Yong, N. Rabin Haematology, University College London Hospitals NHS Foundation Trust, London; Haematology, Oxford University Hospitals NHS Trust, Oxford; Haematology, University Hospital Southampton NHS Foundation Trust, Southampton; Haematology, King’s College Hospital NHS Foundation Trust, London; Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London Background: Pomalidomide is licensed in Europe for patients with relapsed/refractory myeloma, who have received at least two prior therapies (lenalidomide/bortezomib) plus progressed on their last therapy. In the phase 3 NIMBUS study, pomalidomide/dexamethasone (POMA-DEX) was associated with longer PFS (4.0 v 1.9 months) and OS (12.7 v 8.1 months) compared to dexamethasone alone (San Miguel et al 2013). Aims: To assess the real-world clinical efficacy of POMA-DEX in several large UK centres. Methods: Patients had measurable disease (IMWG criteria) and received at 15th International Myeloma Workshop, September 23-26, 2015 least 1 cycle of POMA-DEX. Response was assessed and high risk disease defined as per IMWG. PFS and OS were estimated using Kaplan-Meier method. Results: 79 patients were identified and 62 (78.5%) included in response analyses. All patients received pomalidomide (2-4mg D1-21) /dexamethasone, 30/79 (38%) received another agent(s) [clarithromycin (23), cyclophosphamide (9), carfilzomib (1), bortezomib (1)]. Median age was 67yrs (range 40-89). Median time from diagnosis was 4.9yrs (range 0.5 to 18); median prior therapy lines was 4 (range 1-8). Prior therapies were lenalidomide (100%), bortezomib (98%), thalidomide (84%), ASCT (61%). 73 patients (92%) were refractory to their last therapy, and 58 (73%) were double refractory (bortezomib/IMiDs). Median FU was 6.4 months (0.92-34.5). Median no of cycles was 4 (range 1-32), and median dose 4 mg. In those with starting GFR /1⁄4 SD was achieved in 58/62 (94%). Median PFS was 4.3 months and OS 13.7 months (Figure 1A+B). Reduced GFR (<45ml/min, 14) did not alter PFS (4.0 months v 4.5 months, p1⁄40.44), or OS (10.8 v 13.7 months, p1⁄40.80). High risk patients (11/40, 28%) had similar outcomes to standard risk patients: PFS 3.6 v 4.5 months, (p1⁄40.70) and OS 11.3 v NR (p1⁄40.19). Addition of a 3rd agent (14 patients) did not confer benefit (PFS 4.3 v 4.0 months, p1⁄40.40, OS 7.8 v 13.7 months, p1⁄40.37). Grade 3/4 non-haem toxicities occurred in 27/79 (34%) patients: pneumonia, 15 (19%) and neutropenic