Phase 2 study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma

Abstract Background Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL. Methods This phase 2 study with Simon’s two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Results In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab. Conclusions In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.

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Combination of sintilimab, anlotinib and pegaspargase "sandwich" with radiotherapy in localized natural killer/T cell lymphoma: A multicenter, phase 2 study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7537 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7537-7537

Author(s):

Zhiming Li ◽

Peng Sun ◽

Yu Wang ◽

Hang Yang ◽

Yajun Li ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Risk Group ◽

T Cell Lymphoma ◽

Severe Toxicity ◽

Phase 2 ◽

Newly Diagnosed ◽

Phase 2 Study ◽

Tumor Types ◽

Mild Toxicity

7537 Background: NK/T-cell lymphoma (NKTL) is a rare and distinct subtype NHL. Most newly diagnosed NKTL cases were localized-stage. For localized NKTL, RT alone is inadequate due to high systemic failure rate. Chemoradiation has been increasingly applied. However, current chemotherapy (CT) regimens have severe toxicity and infection, which reduce the completion of RT and patients’ medical compliance. Therefore, novel regimens with mild toxicity are needed. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has showed encouraging antitumor efficacy in pts with r/r NKTL. Anlotinib, a multiple-targeted TKI that mainly blocks VEGF/VEGFR pathway, has been approved for several solid tumor types in china. Anti-angiogenesis therapy could improve efficacy of ICI in multiple tumor types. This multicenter, single-arm, phase 2 study aims to evaluate the efficacy and safety of sandwich chemoradiotion of sintilimab combined with anlotinib and pegaspargase (PEG-ASP) in newly diagnosed localized NKTL pts. Methods: Patients with pathologically confirmed previously untreated stage NKTL were enrolled. All enrolled patients received 3 cycles of sintilimab (200mg D1 ivdrip) combined with anlotinib (12mg po D1-14) and PEG-ASP (2500U/m2 D1) every 3 weeks followed by RT, then received additional 3 cycles of combination therapy as described above. The primary endpoint was overall response rate (ORR) by LUGANO 2014 criteria. Results: A total of 39 pts were enrolled, and 24 pts eligible for response evaluation (70.8% men; median age, 46 y [range 20-64]; 58.3% stage). According to PINK-E system, 8 pts (33.3%) were identified as intermediate risk group and 16 patients were low risk group. 23 of 24 patients completed protocol-specified therapeutic schemes, one patient discontinued the study after the second cycle due to disease progression. ORR was 95.8% (23/24, 95%CI: 76.9%-84.1%). Surprisingly, all the responded patients achieved CR, while 66.7% (16/24, 95%CI: 44.7%-83.6%) patients achieved CR after the second cycle. Median PFS and OS have not been reached. 1-year OS and PFS was 100% and 95.8%, respectively. All grade TRAEs occurred in 84.6% of all enrolled patients and 92.1% were grade 1-2. The most common TRAE was lymphocytopenia (9.9%). Of note, grade 3-4 hematological toxicity was reported in only one patient (4.2%). All AEs were resolved after symptomatic treatment, without systematic corticosteroid intervention. Conclusions: Sintilimab combined with anlotinib and PEG-ASP upfront and after radiotherapy was effective and could be well tolerated in localized NKTL, achieving promising CRR and rapid and long-term remission with mild toxicity. Further investigation of survival outcome is warranted. Clinical trial information: NCT03936452.

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Brentuximab vedotin in The Treatment of Relapsed/Refractory CD30+ Peripheral T‐cell Lymphoma: a FIL Phase 2 Study

Hematological Oncology ◽

10.1002/hon.2963 ◽

2022 ◽

Author(s):

Vittorio Stefoni ◽

Cinzia Pellegrini ◽

Lisa Argnani ◽

Paolo Corradini ◽

Anna Dodero ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Brentuximab Vedotin ◽

T Cell Lymphoma ◽

Phase 2 ◽

Peripheral T Cell Lymphoma ◽

Phase 2 Study

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Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma

Blood ◽

10.1182/blood-2006-12-062877 ◽

2007 ◽

Vol 109 (11) ◽

pp. 4655-4662 ◽

Cited By ~ 138

Author(s):

Youn H. Kim ◽

Madeleine Duvic ◽

Erik Obitz ◽

Robert Gniadecki ◽

Lars Iversen ◽

...

Keyword(s):

T Cell ◽

Clinical Efficacy ◽

Response Rate ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Low Grade ◽

Cutaneous T Cell Lymphoma ◽

Phase 2 ◽

Two Phase ◽

Median Response

Abstract The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4+ CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome [SS], n = 9) received 17 weekly infusions of zanolimumab (early-stage patients, 280 and 560 mg; advanced-stage patients, 280 and 980 mg). The primary end point was objective response (OR) as assessed by composite assessment of index lesion disease activity score. Secondary end points included physician's global assessment (PGA), time to response, response duration, and time to progression. ORs were recorded for patients in both CTCL types (MF, 13 ORs; SS, 2 ORs). In the high-dose groups (560 and 980 mg dose groups), a response rate of 56% was obtained with a median response of 81 weeks. Adverse events reported most frequently included low-grade infections and eczematous dermatitis. Zanolimumab showed marked clinical efficacy in the treatment of patients with refractory MF, with early onset of response, high response rate, and durable responses. The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings.

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E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase I study

Cancer Science ◽

10.1111/cas.13513 ◽

2018 ◽

Vol 109 (3) ◽

pp. 794-802 ◽

Cited By ~ 9

Author(s):

Ken Ohmachi ◽

Kiyoshi Ando ◽

Michinori Ogura ◽

Toshiki Uchida ◽

Kensei Tobinai ◽

...

Keyword(s):

T Cell ◽

Phase I ◽

Phase I Study ◽

Cell Lymphoma ◽

Japanese Patients ◽

T Cell Lymphoma ◽

Cutaneous T Cell Lymphoma

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Brentuximab Vedotin As Single Agent in the Treatment of Relapsed/Refractory CD30 Positive Peripheral T-Cell Lymphoma Patients: A Phase 2 Study of the Fondazione Italiana Linfomi

Blood ◽

10.1182/blood-2020-136917 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 21-21

Author(s):

Vittorio Stefoni ◽

Paolo Corradini ◽

Lorella Orsucci ◽

Stefano Volpetti ◽

Lisa Argnani ◽

...

Keyword(s):

T Cell ◽

Board Of Directors ◽

Cell Lymphoma ◽

Single Agent ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Phase 2 ◽

Advisory Committees ◽

Not Otherwise Specified ◽

Phase 2 Study

Options are limited for patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) for whom the median overall survival (OS) and progression free survival (PFS) are less than 6 months. Patients who are candidates for allogeneic stem cell transplantation can be cured should they achieve adequate response to salvage therapy prior to transplant. Patients who relapse after transplant or who are not transplant candidates are often treated with sequential single-agent therapies with non-curative intent. Only four agents are FDA-approved for the treatment of R/R PTCL including pralatrexate, romidepsin and belinostat. The objective response rate to each of these agents is only 25-30% and duration of response (DOR) is limited. For a specific subtype of PTCL, namely systemic anaplastic large-cell lymphoma, single-agent brentuximab vedotin (BV) treatment resulted in an 86% overall response rate (ORR) and a 57% complete response (CR) rate in R/R disease. A phase 2 study evaluated the efficacy and safety of BV in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified reporting an ORR of 41% (Horwitz et al, Blood. 2014). We conducted a phase 2 study to determine the antitumor efficacy of single-agent BV (1.8 mg/kg administered intravenously every 3 weeks for a maximum of 16 cycles) as measured by the ORR in R/R CD30+ PTCL patients (PTCL not otherwise specified, AITL and transformed mycosis fungoides). Secondary objectives were to assess duration of tumor control, including duration of response and progression-free survival, overall survival and the safety and tolerability of BV in this setting. ClinicalTrials.gov Identifier: NCT02497131. From September 2015 and September 2019, 25 patients were enrolled and 23 (population for the final analysis) received at least one BV infusion (median 5, range 2-16). There were 10 females, 18 patients were in stage IV and 16 subjects were refractory to the last therapy. Median number of therapies received prior to BV was 2 (range 1-6). Final ORR was 30.4%, with 4 CR. CR patients were 3 PTCL not otherwise specified and 1 AITL with response duration of 2.8, 3.3, 4.5 and 10.7 months, respectively. Best response was achieved at the III cycle. PFS was 4.3% at 12 months (median reached at 4.4 months), OS at 12 months was 49.8% (median reached at 11.4 months) and median DOR was 3.4 months. No correlation between CD30 expression per central review and response was observed. Twenty-one hematological toxicities occurred, 14 of them were grade ≥3 (10 thrombocytopenia and 4 neutropenia, all resolved or improved during BV therapy). Among extra-hematological toxicities (n=26, 3.5% grade ≥3), 7 were serious adverse events. To note, 6 of them (23.1%) were lung infection/pneumonia. Only one peripheral neuropathy (grade 1) occurred. In terms of response, the ORR and PFS in this trial are comparable to those in similar populations studied with both other recently approved agents, such as pralatrexate and romidepsin, and with the other phase 2 study on BV. The ORR of 30% and the OS of in the present study places BV among the active agents for PTCL. Safety concerns emerged about infections, claiming for a strict monitoring for these toxicities. Disclosures Corradini: Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Kite: Consultancy, Honoraria; KiowaKirin: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other; BMS: Other; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for. Zinzani:Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Pralatrexate: Phase 1/2 Study in Japanese Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)

Blood ◽

10.1182/blood.v128.22.4157.4157 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4157-4157

Author(s):

Yoshinobu Maeda ◽

Kensei Tobinai ◽

Hirokazu Nagai ◽

Takahiko Nakane ◽

Tatsu Shimoyama ◽

...

Keyword(s):

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

Phase 1 ◽

T Cell Lymphoma ◽

Intermediate Risk ◽

Phase 2 ◽

Western Countries ◽

Phase 2 Study ◽

Previous Phase

Abstract Introduction:Pralatrexate (PDX) is a dihydrofolate reductase inhibitor with high affinity for reduced folate carrier 1 and folylpolyglutamate synthetase, resulting in extensive internalization and accumulation in tumor cells. In the previous phase 2 study for relapsed or refractory (R/R) PTCL in western countries, the overall response rate (ORR) was 29% (32 of 109 evaluable patients [pts]), as assessed by an independent central review (O'Connor et al. JCO 2011). We conducted this phase 1/2 study to evaluate the tolerability, safety, efficacy and pharmacokinetics of PDX in Japanese pts with R/R PTCL. Methods: Eligibility criteria included age ≥20, histologically confirmed PTCL according to the 2008 WHO classification, disease progression after ≥1 prior systemic therapy, ≥1 measurable disease and Eastern Cooperative Oncology Group performance status ≤2. PDX was administered intravenously weekly for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid. There were 2 cohorts in phase 1: Cohort 1 was at 30 mg/m2 of the US-approved dose and Cohort 2 would start at 20 mg/m2 if 30 mg/m2 was not tolerated. The primary endpoint was ORR in phase 2 and secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Response was evaluated by the independent central imaging review using the International Workshop Criteria (Cheson et al. JCO 1999). Cryotherapy and professional oral care (e.g. dental cleaning and oral hygiene instruction) by dentists before and during PDX treatment were recommended to reduce the severity of mucositis. An educational handbook was offered to all pts to learn symptoms, prevention and self-care of oral mucositis. Results:A total of 25 pts received ≥1 dose of PDX and were included in the safety analysis (median age 71 years; 68% male; median of 3 prior therapies; 32% refractory to the most recent therapy; 16% low risk, 48% low-intermediate risk, 24% high-intermediate risk and 12% high risk by International Prognostic Index). Of these, 3 pts were enrolled in phase 1 and 22 pts in phase 2. Two pts in phase 2 were excluded from the efficacy analysis due to lack of a confirmed diagnosis of PTCL by the central pathology review. In phase 1, no dose-limiting toxicity was observed in 3 pts for Cohort 1. In phase 2, using 30 mg/m2 as the recommended dose, the ORR was 45% (9 of 20 evaluable pts in phase 2; 90% CI, 26% to 65%) with 2 complete responses and 7 partial responses achieved in Cycle 1. At the time of data cut-off, median DoR of 9 responders was not reached (range, 1 to 358 days) and 4 responders were still on PDX treatment. The median PFS of all 20 evaluable pts was 150 days (95% CI, 43 to 183). Among 23 evaluable pts for efficacy in phase 1/2, 5 pts had died and median OS was not reached (range, 41 to 570 days) after a median follow-up of 183 days for censored cases. In contrast to the results from the previous phase 2 study in western countries showing the ORR of 8% (1 of 13) in pts with angioimmunoblastic T-cell lymphoma (AITL), the ORR in AITL pts was 44% (4 of 9), which was similar to the ORR in pts with PTCL not otherwise specified (50%; 6 of 12) or pts with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (50%; 1 of 2) in this study. The plasma PDX concentration peaked immediately after intravenous injection over 3 to 5 minutes and the elimination half-life was about 10 to 20 minutes. The most common grade (G) 3 or 4 adverse events were lymphopenia (52%; 13 pts), thrombocytopenia (40%; 10 pts), leukopenia (28%; 7 pts), neutropenia (24%; 6 pts), anemia (20%; 5 pts). Mucositis was observed in 21 pts (84%) including G1 (20%; 5 pts), G2 (44%; 11 pts) and G3 (20%; 5 pts). G4 mucositis did not occur in any pts. Median duration of G2 mucositis was 8 days (range, 3 to 15) and that of G3 was 12 days (range, 8 to 17). According to the criteria for dose modification, the dose of PDX was reduced to 20 mg/m2 due to mucositis in 6 pts. One pt discontinued the treatment due to G2 mucositis recurrence after dose reduction. All 25 treated pts received ≥1 time cryotherapy at PDX administration and 20 of them continued it throughout the study. Thirteen pts received ≥1 time dental scaling or dental cleaning. Conclusion: PDX at 30 mg/m2 weekly for 6 of 7 weeks was effective and well-tolerated in Japanese pts with R/R PTCL. Early oral or dental care potentially ameliorates mucositis and it may be useful for continuing PDX treatment more safely. This study was sponsored by Mundipharma KK. Disclosures Maeda: Mundipharma KK: Research Funding. Tobinai:Ono Pharmaceutical: Research Funding; Takeda: Honoraria, Research Funding; HUYA Bioscience: Honoraria; Daiichi Sankyo Co., Ltd.: Consultancy; Zenyaku Kogyo: Honoraria; SERVIER: Research Funding; GlaxoSmithKline: Research Funding; Kyowa Hakko Kirin: Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding; Chugai Pharma: Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Eisai: Honoraria, Research Funding; Mundipharma KK: Honoraria, Research Funding. Nagai:Mundipharma KK: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding. Nakane:Mundipharma KK: Research Funding. Shimoyama:Mundipharma KK: Research Funding. Nakazato:Mundipharma KK: Research Funding. Sakai:Mundipharma KK: Research Funding. Ishikawa:Mundipharma KK: Research Funding. Izutsu:Eisai: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria; Takeda Pharmaceutical: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Mundipharma KK: Research Funding. Ueda:Kyowa Hakko Kirin: Research Funding; Mundipharma KK: Consultancy.

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Final Clinical Results of a Phase 2 NCI Multicenter Study of Romidepsin in Recurrent Cutaneous T-Cell Lymphoma (Molecular Analyses Included).

Blood ◽

10.1182/blood.v112.11.1568.1568 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1568-1568 ◽

Cited By ~ 5

Author(s):

Susan Bates ◽

Richard Piekarz ◽

John Wright ◽

Robin Frye ◽

William Douglas Figg ◽

...

Keyword(s):

T Cell ◽

Multicenter Study ◽

Drug Exposure ◽

Cell Lymphoma ◽

Clinical Results ◽

T Cell Lymphoma ◽

Cutaneous T Cell Lymphoma ◽

Phase 2 ◽

Molecular Analyses ◽

Grade 3

Abstract Background: Responses to the novel HDAC inhibitor romidepsin were observed in patients (pts) with T-cell lymphoma in a phase 1 NCI trial. Aims: To evaluate the efficacy and tolerability of romidepsin in the treatment of advanced cutaneous T-cell lymphoma (CTCL). As an exploratory endpoint, to examine the molecular effects of romidepsin in both CTCL and peripheral T-cell lymphoma (PTCL). Methods: This Phase 2, open-label, multi-arm, multicenter study enrolled 71 CTCL pts from the NCI and 9 extramural sites. PTCL pts were also enrolled. Clinical results for pts with CTCL and biomarker analyses for both PTCL and CTCL are presented here; clinical results for the PTCL pts are presented elsewhere. This study is now closed to accrual. Pts with recurrent CTCL (Stages IA-IVB) received romidepsin at 14 mg/m2 as a 4-hr infusion on days 1, 8 and 15 q 28 days. Responses were assessed using a composite endpoint that evaluated overall changes in skin (modified Physicians Global Assessment), lymph nodes, extranodal visceral lesions and abnormal circulating T-cells. Molecular endpoints evaluated in NCI pts were: histone acetylation in peripheral blood mononuclear cells (PBMCs); MDR-1 gene expression in PBMCs and in biopsy samples; and blood fetal hemoglobin levels. Results: 71 pts (48 men and 23 women) with a mean age of 56 yrs (range 28–84) were enrolled and received romidepsin; 63 pts received ≥2 cycles of therapy. Mean number of prior therapies was 3.4 (range 1–10). Objective disease response rates (ORR) are presented in the table. Overall disease control (CR+PR+SD90) was 62% in all pts and 70% in pts who received ≥2 cycles. Target skin lesions were followed and changes were generally similar to overall skin changes. Median duration of response (DOR) was 11 months (mo) and the maximum DOR as of data cut-off was 5.5+ yrs. The most frequent drug-related AEs (all grades, all cycles) were generally mild, including nausea (82%; 4% ≥grade 3), fatigue (73%; 14% ≥ grade 3), electrocardiogram T-wave amplitude decreased (69%, 0% ≥grade 3); hemoglobin decreased (59%, 9% ≥grade 3), and platelet count decreased (59%; 13% ≥grade 3). Six pts died within 30 days of study drug administration: 2 after salvage chemotherapy, 1 with ARDS due to PD, 2 with infection, and 1 of unknown cause; 2 of these deaths were considered possibly related to treatment. An increase in all biomarkers measured was observed, although not in all pts. Correlation between global histone H3 acetylation (AcH3) at the 24-hr time point and Cmax, AUC, and clearance was observed (r = 0.37, 0.36, and −0.44, respectively, p = 0.03). Pts with major responses were more likely to have higher levels of AcH3 at 24 hr. Conclusions: This study demonstrates tolerability and durable clinical benefit (ORR of 35% and median DOR of 11 mo in all pts) of romidepsin in pts with recurrent CTCL. Significant responses were observed at all stages of disease, including an ORR of 32% in all pts with stage ≥IIB and 20% in all pts with stage IV. Time to response was rapid, within 2 mo in most pts, and responses were durable, >6 mo in most pts. Molecular analyses confirmed that romidepsin inhibits its target deacetylases in pts. Increases were not observed in all pts, perhaps reflecting, in part, variable drug exposure or variable response to HDAC inhibition. Correlation of global acetylation with PK parameters suggests that increased drug exposure results in increased global acetylation. All Pts N=71 Pts ≥ 2 cycles N=63 ORR (CR+PR), n (%) 25 (35%) 25 (40%) PR, n (%) 21 (30%) 21 (33%) CR, n (%) 4 (6%) 4 (6%) SD90, n(%) 19 (27%) 19 (30%) Overall disease control (CR+PR+ SD90) 44 (62%) 44 (70%) DOR 11 (1+ mo, 5.5+ yrs) 11 (1+ mo, 5.5+ yrs) OR for pts with stage ≥ IIB, n (%) 20/62 (32%) 20/55 (36%) SD90= stable disease for ≥90 days

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