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e19048 Background: PTCL are rare diseases with a poor prognosis. Front line therapy achieves CR in 30% to 60% and OS of 25%. Patients with R/R disease have an even worse prognosis. There is no consensus on the management of R/R disease because evidence supporting most treatment approaches is modest. Many approaches are often not supported by literature, and categorizations regarding efficacy and toxicity without attention to details are ignored. Treatments that have achieved regulatory approval with stringent independent assessment of pathology and response are viewed as less established, or equivalent to smaller published experiences. In the effort to take a critical and comprehensive evidence-based approach to available standards in R/R PTCL we developed an objective scoring system for all types of studies published in the literature (eg randomized phase 3, case match control, phase 2, phase 1, case reports and small series) to aid decision-making based on an assessment of all the available data. Methods: An extensive review on PubMed of clinical trials published in literature for R/R PTCL was performed. A rigorous scoring system based on a survey from 100 authorities in the field to quantitate scientific impact of each study based was developed. These include: type of study (randomized phase 3, case match control analysis, phase 2 weighted based on number of PTCL patients [ > 100 vs < 100 patients], phase 1 with > 5 or < 5 PTCL patients enrolled, and retrospective); weighting for use of central pathology or response review; weighting for detailed study metrics (ORR, CR, DoR, PFS). The scoring system included a penalty for omission detail. The proposed scoring system was evaluated by a panel of experts. The scoring system was modified based on recommendations made by 2 or more panel members. Results: We identified 58 publications between 2004 and 2018. The scoring system spanned from 0 to 9. Only 12 of the 58 studies had a score above 5; 15 of 58 had a score between 1 - 5; remaining publications scored 0 - 1. Conclusions: Our analysis suggests practice patterns are based on studies with low priority scores, and underweight robust clinical experiences. This analysis aims to produce an evidenced based approach for R/R PTCL.

Purpose Adult T-cell leukemia-lymphoma (ATL) is usually resistant to conventional chemotherapies, and there are few other treatment options. Because CC chemokine receptor 4 (CCR4) is expressed on tumor cells from most patients with ATL, KW-0761, a humanized anti-CCR4 monoclonal antibody, which markedly enhances antibody-dependent cellular cytotoxicity, was evaluated in the treatment of patients with relapsed ATL. Patients and Methods A multicenter phase II study of KW-0761 for patients with relapsed, aggressive CCR4-positive ATL was conducted to evaluate efficacy, pharmacokinetic profile, and safety. The primary end point was overall response rate, and secondary end points included progression-free and overall survival from the first dose of KW-0761. Patients received intravenous infusions of KW-0761 once per week for 8 weeks at a dose of 1.0 mg/kg. Results Of 28 patients enrolled onto the study, 27 received at least one infusion of KW-0761. Objective responses were noted in 13 of 26 evaluable patients, including eight complete responses, with an overall response rate of 50% (95% CI, 30% to 70%). Median progression-free and overall survival were 5.2 and 13.7 months, respectively. The mean half-life period after the eighth infusion was 422 ± 147 hours (± standard deviation). The most common adverse events were infusion reactions (89%) and skin rashes (63%), which were manageable and reversible in all cases. Conclusion KW-0761 demonstrated clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. Further investigation of KW-0761 for treatment of ATL and other T-cell neoplasms is warranted.

Purpose To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy. Patients and Methods Treatments comprised concurrent radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC). Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status (PS) of 0 to 2 were eligible for enrollment. The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose. Results Of the 33 patients enrolled, 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose. Twenty-seven patients (range, 21 to 68; median, 56 years) treated with the recommended dose showed the following clinical features: male:female, 17:10; stage IE, 18; stage IIE, 9; B symptoms present, 10; elevated serum lactate dehydrogenase, 5; and PS 2, 2. With a median follow-up of 32 months, the 2-year overall survival was 78% (95% CI, 57% to 89%). This compared favorably with the historical control of radiotherapy alone (45%). Of the 26 patients assessable for a response, 20 (77%) achieved a complete response, with one partial response. The overall response rate was 81%. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed. Conclusion Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.

e19070Background: Polatuzumab vedotin (PoV) is an antibody-drug conjugate (ADC) that contains a humanized anti-CD79b monoclonal antibody and a potent anti-mitotic agent, monomethyl auristatin E (MM...

e19018Background: The programmed death-1 (PD-1) immune checkpoint pathway regulates T-cell-mediated antitumor immune responses in various tumors. Nivolumab (Nivo) (Ono Pharmaceutical, Bristol-Myers...

e19057Background: The Lugano Classification incorporating FDG-PET/CT in the staging and response assessment of lymphomas was published (JCO 2014). We previously reported that there was some non-neg...

7506Background: The goal of PILLAR-2 (NCT00790036) was to reduce DLBCL relapse by providing 1 year of adjuvant EVE to poor-risk (International Prognostic Index [IPI] ≥3) pts who had achieved a CR with R-chemo. Methods: PILLAR-2 was a multicenter double-blind, placebo (PBO)-controlled, phase 3 study. Pts with histologically confirmed stage III/IV poor-risk (IPI ≥3) DLBLC who had a PET/CT-confirmed CR to first-line R-chemo were randomized 1:1 to EVE 10 mg/day or PBO for 1 year or until disease relapse, unacceptable toxicity, or death. The primary endpoint was disease-free survival (DFS) by local assessment using revised IWRC; secondary endpoints were overall survival (OS), lymphoma-specific survival (LSS), and safety. Results: Median study follow-up was 50.4 months (range, 24.0–76.9 months). Of the 742 pts randomized, 177 (48%) pts in the EVE and 249 (67%) in the PBO arms completed the study treatment as per protocol. Overall, 47% pts were ≥65 years, 50% were male and 42% had an IPI of 4+5. Adjuvant EVE did...

e19056Background: ATL, a rare but aggressive peripheral T-cell malignancy caused by HTLV-1, occurs more frequently in regions where HTLV-1 infection is endemic and may differ by geographical locati...

7542Background: Forodesine, a potent purine nucleoside phosphorylase inhibitor, induces apoptosis mainly in T cells. Forodesine at relatively low dose was feasible but the response rate was not suf...

e19050Background: No clinical evidence is available about the bendamustine and rituximab (BR) regimen as the first-line treatment of indolent B-cell non-Hodgkin lymphoma (B-NHL) or mantle cell lymp...

TPS8603 Background: The immunomodulatory drug, lenalidomide (Revlimid), has both anti-inflammatory and antiangiogenic properties. In preclinical studies, the immunological function of tumor-infiltr...

8565 Background: Although HDAC-containing CTX with rituximab (R) followed by high-dose CTX (HDC) with autologous stem cell transplantation (ASCT) has been recommended in younger untreated MCL patie...

8506 Background: Mogamulizumab (Moga), a defucosylated humanized anti-CCR4 antibody, was approved for the treatment of relapsed/refractory ATL in Japan in 2012. This multicenter, randomized, phase II trial was conducted to examine the efficacy of the combination of Moga with standard chemotherapy for untreated aggressive ATL. Methods: Previously untreated patients (pts) with CCR4-positive ATL were randomly assigned to receive mLSG15 plus Moga (arm A) or mLSG15 alone (arm B). The primary endpoint was CR rate (%CR), and secondary endpoints included ORR, PFS, OS and safety. Pts received 4 courses of mLSG15 regimen, with or without a total of 8 doses of Moga (1.0 mg/kg) once every 2 weeks. The planned sample size, 22 pts per arm, provided a probability of 80% that %CR in arm A would have larger %CR when true %CR for arm A is 15% better than that for arm B. Results: Of 54 pts randomized, 53 were treated (arm A: 29; arm B: 24). Male/female ratio was 53/47%, median age was 63 (37-81), and subtype was acute/lymphoma/unfavorable chronic, 70/25/6%. %CR and ORR in arms A and B was 52% (95%CI [CI]; 33, 71) vs. 33% (CI; 16, 55) and 86% (CI; 63, 96) vs. 75% (CI; 53, 90), respectively. The results in arm B were similar to the previously reported %CR of 40% and ORR of 72% with mLSG15 (Tsukasaki et al, JCO 2007). ORR according to the disease subtype, in arms A and B, was 55% vs. 29% for acute, 50% vs. 43% for lymphoma and 33% vs. 0% for unfavorable chronic. Median PFS was 259 days (CI; 197, -) for arm A and 192 days (CI; 147, -) for arm B. Median OS was not reached in both arms. The most common treatment-related AEs in each arm were neutropenia (100%, 96%), thrombocytopenia (100%, 96%), leukopenia (100%, 92%), lymphocytopenia (97%, 96%), anemia (97%, 92%) and febrile neutropenia (90%, 88%). In arm A, skin disorders were more frequent but manageable, and no serious skin disorder like Stevens-Johnson syndrome was observed. There was one treatment-related death, which was not related to Moga. Conclusions: The combination of Moga with mLSG15 was well tolerated and the study met its primary endpoint. These results suggest that Moga with mLSG15 is a rational treatment option for newly diagnosed aggressive ATL. Clinical trial information: NCT01173887.

8551 Background: BM-ca is a novel humanized type-I/II anti-CD20 antibody, which is effective against rituximab-resistant cell line RC-K8, and has more potent anti-cell-proliferation activity than rituximab or ofatumumab when combined with cancer chemotherapeutics. The aim of this study was to evaluate the safety, efficacy, and PK profile of BM-ca in pts with indolent B-NHL. Methods: A total of 12 pts {age: median 61 (50-73), number of prior regimens: median 2 (1-13)} with indolent B-NHL relapsed after or refractory to rituximab-containing therapy underwent treatment by IV infusion of BM-ca weekly for 4 weeks at a dose of 5, 10, or 15 mg/kg. Initially, 3 pts were to undergo BM-ca therapy at a dose of 5 mg/kg using the conventional 3+3 dose escalation design. To minimize infusion reactions (IRs), pts were pretreated with acetaminophen and d-chlorpheniramine maleate. Allopurinol and/or hydrocortisone were also administered if necessary. Infusion was started at 50 or 100 mg/h and was gradually increased to a maximum of 400 mg/h. Since no DLTs were observed, all 12 pts completed weekly 4 doses of BM-ca. Results: The most frequent AE was IRs (11 of 12 pts), which occurred mostly in the first infusion, and the highest grade of AE was neutropenia (grade 4 in one pt of 15 mg/kg after the last infusion). Anti-BM-ca antibodies were not detected. Of the 12 pts examined, 2 achieved CR (10 mg/kg) and 2 PR (15 mg/kg); these 4 pts had follicular histology. The remaining 8 pts including one each of extranodal marginal zone, nodal marginal zone, and small lymphocytic histology were judged to achieve SD. The CR states in 2 pts continued at least >14 and >11 months, respectively. The PK properties of BM-ca were comparable to those of other naked anti-CD20 antibodies including rituximab (AUC and Cmax were proportional to the doses; Vdss≈4 L; t1/2≈750 h). Since at 10 mg/kg the response was the best and no grade 4 AE observed, 10 mg/kg was suggested as a recommended phase II dose. Conclusions: Four weekly IV administration of BM-ca up to 15 mg/kg was well tolerated and safe with promising preliminary anti-lymphoma activity in pts with indolent B-NHL. Further evaluation is warranted. Clinical trial information: 000004805.

8050 Background: Concurrent chemoradiotherapy has been regarded as one of the standard management for localized nasal NKTCL. However, its long-term efficacy and toxicity is not known. Methods: The JCOG0211 trial is a phase I/II study of concurrent chemoradiotherapy consisting of radiotherapy (RT) of 50 Gy and 3 cycles of DeVIC (carboplatin, etoposide, ifosfamide, dexamethasone) for newly diagnosed, localized nasal NKTCL (JCO 2009). Patients (Pts) with newly diagnosed, localized diseases (IE & contiguous IIE with cervical node involvement) who were 20-69 yrs of age with PS 0-2 were eligible. 3-D conformal RT planning with a wide margin (+ 2 cm to the gross tumor, the entire nasal cavity and the nasopharynx) and a 2-step cone down were required. 33 pts were enrolled in the study, 27 of whom were treated with RT and a 2/3-dose of DeVIC, which was selected as the recommended phase II dose in the preceding phase I portion of the trial. All pts completed RT without any protocol violations. Long-term follow-up results on overall survival (OS), progression-free survival (PFS) and toxicity were evaluated. Results: The median follow-up was 69 months (range, 62-96). The pt (N=33) characteristics were as follows: median age 54 yrs (range, 21-68); stage IIE 33%; B symptom (+) 36%; elevated serum LDH 21%. %5-yr OS and PFS were 73% (95%CI, 54-85%) and 67% (95%CI, 48-80%), respectively. 11 pts (33%) experienced disease recurrence. Two achieved a 2nd CR by salvage chemotherapies followed by allogeneic stem cell transplantation, and the remaining 9 pts died of disease. There was no observed death and disease progression after 34 and 31 months, respectively. One pt experienced Grade 3 irregular menstruation for 3 years. No other Grade 3 or 4 late non-RT-associated adverse events (AEs) were observed. One pt received plastic surgery due to Grade 4 RT dermatitis. No other Grade 3 or greater RT-associated late AEs were encountered. Conclusions: Both survival benefit and disease control from concurrent chemoradiotherapy with RT and DeVIC are maintained during a 5-yr follow-up, indicating the excellent efficacy of this approach as a first-line therapy for localized nasal NKTCL. Long-term toxicity is acceptable.

8029 Background: Most pts with indolent B-NHL relapse even after rituximab-containing chemotherapy. Vorinostat is an orally active histone deacetylase (HDAC) inhibitor, and is under investigation as monotherapy or in combination regimens in various hematologic malignancies. It has been reported that the histone acetyltransferase genes (EP300 and CREBBP) are frequently mutated in NHL, suggesting the potential usefulness of HDAC inhibitors in its treatment. Methods: We conducted a phase 2 study to investigate the efficacy, safety and tolerability of vorinostat in pts with indolent B-NHL or MCL with the overall response rate (ORR) against follicular lymphoma (FL) as the primary endpoint. The primary hypothesis was to demonstrate the efficacy in FL pts as measured by the ORR. Assuming the true ORR with vorinostat of 50% and without vorinostat of less than 25%, 39 pts will provide 90% power to demonstrate an ORR>25%. Vorinostat was administered at the dose of 200 mg BID for 14 consecutive days in a 21-day cycle. The ORR and PFS were determined by an independent review panel in the Full Analysis Set (FAS) population. Results: A total of 56 pts with a median age of 60 years (range: 33 - 75) were enrolled, and 50 of them (39 with FL, 11 with other subtypes of indolent B-NHL or MCL) were included in the FAS population. The number of prior therapeutic regimens was 2 (range: 1 - 4) and 41 pts have previously received rituximab-based regimens.. The percentages of pts with FLIPI at low risk, intermediate risk and high risk were 41%, 39%, and 21%, respectively. The ORR in 39 pts with FL was 49% (95% CI: 32, 65), and the pre-specified statistical success criterion was met. The median PFS in 39 pts with FL was 17.5 months (range: 2, 22+), especially the median PFS in 19 responders with FL has not yet been reached. The major toxicities were hematologic and gastrointestinal ones, which were reversible and manageable. Grade 3/4 infection was observed in 2%. Conclusions: This phase 2 study demonstrated that oral vorinostat is an agent with sustained antitumor activity in pts with relapsed or refractory indolent B-NHL, with acceptable safety profiles, warranting further investigations.

8023 Background: Effective salvage therapies are needed in patients (pts) with relapsed/refractory DLBCL after R-CHOP. Therapy with bendamustine plus rituximab (B-R) was well tolerated and effective in the preceding phase I study in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, including DLBCL. This phase II study assessed the efficacy and safety of B-R in pts with relapsed/refractory DLBCL. Methods: Pts with histologically confirmed DLBCL (excluding transformed disease) and 1-3 prior therapies received rituximab 375 mg/m2 IV on day 1 and bendamustine 120 mg/m2 IV on days 2 and 3 of each 21-day cycle, for up to 6 cycles. Recovery of neutrophil count to ≥1,000/mm3 and platelet count to ≥75,000/mm3 were required prior to the start of each cycle; treatment delays >2 weeks resulted in discontinuation. The primary endpoint was overall response rate (ORR); secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and safety. Results: A total of 63 pts were enrolled; data from 59 pts were available. Median age was 67 (range, 36-75) years with 37 pts over 65 years. The majority of pts (64.4%) had 1 prior therapy; 57 pts (96.6%) were previously treated with rituximab-containing combination chemotherapy and 8 (13.6%) had prior auto-PBSCT. Pts received a median of 4 (range, 1-6) treatment cycles. Sixteen (27.1%) pts completed 6 treatment cycles; most common reasons for early discontinuation were disease progression (n=15) and failure to meet criteria to start the next cycle (n=13). Among 59 pts evaluable for response, ORR was 62.7% with a 37.3% CR rate. The median PFS was 200 days (95% CI, 109-410). Most common grade 3/4 adverse events (AEs) included CD4 lymphocytes decreased (66.1%), neutropenia (54.2%), and thrombocytopenia (10.2%). Four (6.8%) pts discontinued due to serious AEs (cytomegalovirus infection, infection, pneumonia, and pneumonia/respiratory failure). Conclusions: B-R demonstrated promising activity in pts with relapsed/refractory DLBCL. Toxicity was primarily hematologic and generally manageable. These results suggest that B-R is a promising salvage regimen for pts with relapsed/refractory DLBCL after R-CHOP.

e18510 Background: To evaluate the efficacy and safety of R × 8 dosing monotherapy in pts with relapsed or refractory indolent B-cell NHL with pharmacokinetic (PK) assessment. Methods: In a multi-c...

e18525 Background: OFA is a human IgG1 monoclonal antibody that recognizes a unique epitope encompassing the small and large loop of CD20. OFA was recently approved by the U.S. FDA for treatment of CLL refractory to fludarabine and alemtuzumab based on a pivotal study of a 2,000 mg dose. Methods: We conducted an open-label, nonrandomized, multicenter, phase I study to evaluate the tolerability, safety, efficacy and pharmacokinetics (PK) of OFA monotherapy in JPN pts with CD20-positive, relapsed/refractory CLL, SLL or follicular lymphoma. Pts received 300 mg of OFA at the 1st infusion, followed by 7 weekly infusions of 500 mg (level 1) or 1,000 mg (level 2). The primary endpoint was to determine toxicity including dose-limiting toxicity (DLT). Results: Baseline characteristics are summarized in the Table. All pts completed 8 planned doses. No DLT or serious Adverse Events (AEs) was observed. The investigator reported grade 3-4 AEs were grade 3 lymphopenia (n=1) and neutropenia (n=1). All pts had a grade 1-...

e18552 Background: GA101 is the first fully humanized and glycoengineered type II monoclonal anti-CD20 antibody. Previously, GA101 monotherapy has shown similar safety to rituximab and promising ef...

e18540 Background: Bendamustine hydrochloride is a purine analog/alkylator hybrid agent with a unique mechanism of action. Although bendamustine with or without rituximab has been shown to be effec...

8549 Background: Nasal NK/T-cell lymphoma is rare and its standard therapy has not been established. Tumor cells express P-glycoprotein concerning multi-drug resistance (MDR). Anthracycline-containing chemotherapy is not effective and %2-yr overall survival (OS) of radiotherapy (RT) alone is only 45%. Methods: To explore a more effective treatment for localized nasal NK/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy consisted of 50 Gy of RT and 3 courses of DeVIC [carboplatin (CBDCA), etoposide (ETP), ifosfamide (IFM), dexamethasone (DMS)]. Patients (Pts) with newly-diagnosed, localized (IE & contiguous IIE with cervical node involvement) diseases, 20–69 years of age and PS 0–2 were eligible. The 3-D conformal RT planning was required to cover adequately target volumes (2 cm margin to gross tumor, entire nasal cavities and nasopharynx) and to minimize doses to organs at risk. Primary endpoint of the phase II portion was 2-yr OS and the enrollment of 24 pts to the phase II portion was planned. Based on the results of the phase I portion (ASH 2005, #2685), 2/3-dose of DeVIC (CBDCA 200mg/m2 d1 IV, ETP 67mg/m2 d1–3 IV, IFM 1.0g/m2 d1–3 IV, DMS 40mg/body d1–3 IV; every 3 wks) was applied for the phase II portion. RT quality assurance review confirmed no protocol violation (ASTRO 2008, #2682). Results: From Sep 2003 to Dec 2006, 33 pts were enrolled in the phase I/II study. 27 pts evaluated in the phase II portion showed the following features: age 21–68 yrs (median 56), M:F=17:10, stage IE 18, stage IIE 9, B symptom (+) 10, elevated serum LDH 5, PS2 2. With a median follow-up of 32 months (range, 24–62), %2-yr OS was 78% (95% CI, 57–89). Of 26 pts evaluable for response, 20 achieved CR, 1 PR, 2SD, and 3PD. %CR and %ORR were 77% (95% CI, 56–91) and 81%, respectively. The most common grade 3 non-hematologic toxicities were mucositis due to RT (30%) and infection (30%). Grade 4 hyponatremia and dermatitis due to RT were observed in each 1 pt. No treatment-related death was observed. Conclusions: Concurrent chemoradiotherapy using MDR-non-related agents and ETP is a safe and effective treatment for localized nasal NK/T-cell lymphoma, providing the basis for subsequent studies. No significant financial relationships to disclose.

8616 Background: R-CHOP is regarded as one of the most effective initial treatments for indolent B-cell Non-Hodgkin lymphoma (B-NHL); however, the information on its long term outcome is limited. Methods: Sixty-nine patients (pts) with untreated indolent B-NHL of advanced stages were randomized in the concurrent or sequential combinations of R-CHOP. Pts in the concurrent arm (Arm C) received 6 times of R (375 mg/m2), 2 days prior to each cycle of CHOP, and pts in the sequential arm (Arm S) received weekly 6 times of R (375 mg/m2) following 6 cycles of CHOP. No maintenance therapy was given in both arms. The last pt was enrolled in July, 2000, and the planned observation was completed in May, 2007. Results: A total of 69 pts were randomized but 2 were withdrawn before receiving treatment because of neutropenia or concomitant cancer. Sixty-five pts (94%) had follicular lymphoma, and 31 pts were in low, 27 in intermediate and 11 in high risk group according to the Follicular Lymphoma International Prognostic...

18521 Background: Vorinostat (Zolinza™), a potent histone deacetylase inhibitor, has demonstrated clinical activity in pts with cutaneous T-cell lymphomas (CTCL) and other NHL subtypes. However, the clinical activity and PK profile in Japanese pts with NHL was unknown. Methods: Japanese pts with NHL were sequentially enrolled in two dose levels ranged from 100 (Level 1) - 200 mg (Level 2) BID, PO for 14 consecutive days every 3 wks. Higher doses were not tested as other phase I studies had established that 300 mg BID for 14 consecutive days every 3 wks exceeded the MTD. PK profiles were analyzed in serum and urine samples. Response was also evaluated according to the international workshop criteria. Results: Ten pts were enrolled: 9 were evaluable for toxicity. One was excluded due to noncompletion of the 1st cycle. All were evaluable for PK. Median age was 60 yrs (range 52–74). Four pts had follicular lymphoma (FL), 2 mantle cell lymphoma (MCL), 2 diffuse large B-cell lymphoma and 2 CTCL. Median no. of prior regimens was 3 (1–4). In the 1st cycle, none of 3 pts at Level 1 and 1 of 6 pts at Level 2 developed DLTs (anorexia and hypokalemia of grade 3), indicating Level 2 to be the MTD in this setting. PK was not greatly affected by multiple doses. Intact drug was hardly excreted in urine ( No significant financial relationships to disclose.

17515 Background: Dasatinib is a potent, orally active, multi-targeted kinase inhibitor of BCR-ABL and SRC family kinases. Studies outside Japan have shown dasatinib to be highly effective in overcoming resistance and intolerance to imatinib, inducing durable cytogenetic (CyR) and hematologic responses (HR) in this population. The maximum tolerated dose was not reached in the Phase-I trial outside Japan and a 70-mg BID dose was determined to provide the optimal benefit-risk profile. Methods: This Phase-I/-II study was designed to assess the safety and efficacy of dasatinib in Japanese patients with imatinib-resistant or -intolerant CML or Ph+ALL. In the 4-week Phase-I portion in patients with chronic-phase (CP) CML, three dose levels were evaluated: 50 mg, 70 mg, and 90 mg BID. The Phase-II portion is currently evaluating the CyR of dasatinib in patients with CP-CML at 24 weeks, and the HR rate in accelerated- (AP) or blast-phase (BP) CML and Ph+ ALL at 12 weeks. Results: As of December 2006, 17 eligible patients have been treated in Phase I. Six patients (4F, 2M; median age 43 y [range 27–56]) were treated with 50 mg BID and 1 dose-limiting toxicity (DLT) was observed (Grade 4 thrombocytopenia). Two patients experienced transient Grade 3 ALT elevations but as treatment was uninterrupted, these were not considered DLTs. Six patients (6M; median age 42 y [range 27–55]) were treated with 70 mg BID and again 1 DLT was observed (Grade 4 thrombocytopenia). No DLT has been observed among 4 patients (3M, 1F; median age 41 y [range 27–64]) at the 90-mg BID dose. Major CyRs have been achieved in all three cohorts in the Phase-I segment of the trial. Thirty six patients were enrolled and treated in the Phase-II part of the trial (12 CP-CML, 7 AP- CML, 4 BP-CML, and 13 Ph+ALL). Efficacy and safety data as well as the baseline BCR-ABL mutation data are currently being assessed and will be presented. Conclusions: Dasatinib can be safely administered at doses of up to 90 mg BID to Japanese patients with imatinib-resistant or -intolerant CP-CML. No significant financial relationships to disclose.

7593 Background: Although POAML is a recently recognized distinct entity, its natural history, prognostic factors, behavior of progression and death, and standard initial management have not been fully elucidated. Methods: 114 pts with a histologically verified POAML treated at our institution between 1970 and 2003 were retrospectively analyzed. Results: With a median follow-up duration of 5.7 years (0.6–34.0), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10 years was 89% and 57%, respectively. Older pts (>60) showed significantly worse OS (p=0.002). However, other clinical factors did not affect significantly OS or PFS. 13 (11%) pts died, but only 3 (3%) due to progressive lymphoma. 31 (27%) pts progressed, 7(6%) at systemic diseases, 8 (7%) at contra lateral sites, and 16 (14%) at the same sites, and only 2 (2%) transformed high-grade lymphoma. All 8 pts who progressed at contra lateral sites were limited to those who had involved initially in the orbit (p=0.036) and their time to progression was significantly longer (p=0.039). Pts who received initially radiation-containing therapy were superior in PFS but not OS than those initially treated with other modalities (p=0.016 and 0.091, respectively). Moreover, when we compared the outcomes of no initial therapy cohort and immediate therapy cohort, there was no significant difference in OS and PFS (p=0.499 and 0.073, respectively). Conclusions: The majority of pts with POAML showed the behaviors of very indolent diseases, and only age was significant prognostic factor. Our preliminary observation suggesting that no initial therapy is an acceptable approach for selected pts (Ann Oncol 2006;17:135–40) was further confirmed in this study for all cohorts. Considering the possible heterogeneity of POAML among initial sites suggested by the present study and the genetic heterogeneity revealed by our previous study (Blood 2005;106:289a), further investigations on POAML are warranted. No significant financial relationships to disclose.

17561 Background: It is challenging to conduct a high quality multi-institutional clinical trial for localized nasal NK/T-cell lymphoma due to the anatomical complexity and its rarity. The purpose of this study was to evaluate the compliance with protocol guidelines in concurrent chemoradiotherapy for this disease among radiotherapy institutions participating in a multi-center phase I/II JCOG trial 0211. Methods: The treatment consisted of radiotherapy 50 Gy and 3 cycles of DeVIC chemotherapy [carboplatin, etoposide, ifosfamide, dexamethasone] (Yamaguchi M, et al.: Proc ASH, 2005). CT-based three-dimensional treatment planning was required to cover adequately target volumes and to minimize doses to organs at risk such as the eyes, the brain stem and the spinal cord. Patient data were sent to the review center after the treatments have been finalized. The following parameters were evaluated by the quality assurance review board: treatment records and charts; simulation films; portal images; prescribed dose; dose fractionation and overall treatment time; dose distributions; and dose to risk organs. Results: At the time of phase I analysis, 10 patients were enrolled in this study. In 2 of 10 cases, process of treatment planning was not available. There was no protocol violation. Major deviations were identified as follows: Delineation of clinical target volume (< 2 cm from the edge of the gross tumor volume at any direction), 2/10; dose distribution (not covered by 90%-115% isodose line), 1/10; and dose to optic chiasm (>40 Gy), 1/10. All cases were compliant in prescribed dose, dose fractionation, and overall treatment time. In the last 4 of 10 cases, attending radiation oncologists at the participating institutions were contacted by the radiation oncology study chair and they discussed the treatment planning just after patient enrollment. These 4 cases were all protocol compliant compared to 6 cases with 4 major deviations. Conclusions: Individual case review is essential in a multi-center clinical trial to keep enrolled cases protocol compliant and minimize inter-institutional variations. We expect that our quality assurance program will maintain the quality of the JCOG trial 0211. No significant financial relationships to disclose.

6703 Background: To confirm the efficacy and safety of standard CHOP therapy in Japanese pts with L or L-I risk aggressive NHL, we conducted a multicenter phase II study with overall survival (OS) ...

6686 Background: Numerous clinicopathologic studies of MLBCL have been reported from US and European countries; however, only a few case-series of at most 10 cases are available from Japan and othe...

6577 Background: R-CHOP is regarded as the best available treatment for untreated patients (pts) with indolent and aggressive B-NHL; however, the optimal combination schedule in indolent B-NHL remains unknown. Methods: Previously untreated pts with indolent B-NHL of advanced stages were randomly allocated to the concurrent arm (Arm C) or the sequential arm (Arm S). All pts received 6 cycles of standard CHOP every 3 weeks. In addition, Arm C received R at 375 mg/m2, 6 times, 2 days prior to each cycle of CHOP, whereas Arm S received R at 375 mg/m2, weekly 6 times, following 6 cycles of CHOP. Pts were monitored for clinical response by the International Workshop Criteria, molecular response by PCR assay for bcl-2 rearrangement in bone marrow and peripheral blood, and adverse events for at least 3 years or until progression. The primary endpoint was the overall response rate (ORR). Results: Between July 1999 and July 2000, a total of 69 pts were enrolled, and 66 (Arm C, 32; Arm S, 34) of them were eligible. ...

6704 Background: Optimal combination schedule of R-CHOP for untreated FL is still uncertain. Quantitative evaluation of MRD may suggest a correlation between the treatment schedule and its outcome. Methods: We conducted a randomized phase II study comparing 6 cycles of R-CHOP (concurrent; Arm C) and 6 cycles of CHOP followed by weekly 6 doses of rituximab (sequential; Arm S) for previously untreated, advanced-stage indolent B-cell lymphoma, mainly consisting of FL. DNA of bone marrow (BM) and peripheral blood (PB) were obtained before treatment (baseline), after 3 cycles and 6 cycles of R-CHOP/CHOP, and 4 months after R-CHOP/CHOP followed by rituximab (4 mo). Bcl-2/JH translocation was amplified and quantified by real-time PCR. Results: Sixty-five (94%) of 69 enrolled patients (pts) were diagnosed as having FL by the central pathology review. Bcl-2(MBR)/JH translocation in BM and/or PB were detectable in 27 pts (14 pts in Arm C and 13 pts in Arm S). Faster decrease in bcl-2/JH copy numbers, and thus highe...