First Report of a Phase II Clinical Trial of Lenalidomide Oral Therapy for Peripheral T-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2579-2579 ◽  
Author(s):  
Tony Reiman ◽  
Daygen Finch ◽  
Neil Chua ◽  
Darrell White ◽  
Douglas A. Stewart ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Median Number ◽  
T Cell Lymphoma ◽  
Refractory Disease ◽  
Peripheral T Cell Lymphoma ◽  
Grade 3 ◽  
Experienced Grade

Abstract BACKGROUND: Lenalidomide has immunomodulatory and anti-neoplastic properties, with demonstrated activity in myelodysplastic syndrome and multiple myeloma. Preliminary reports indicate that lenalidomide has activity against cutaneous T-cell lymphoma (mycosis fungoides) and chronic lymphocytic leukemia. We hypothesized that lenalidomide should be studied as a non chemotherapy approach for Peripheral T- Cell Lymphoma (PTCL). STUDY DESIGN AND METHODS: In this Canadian multi-center, open label, single-arm, phase II clinical trial, patients with PTCL were treated with lenalidomide 25 mg po qd × 21 days on a 28-day cycle until disease progression, death or unacceptable toxicity. Patients with ECOG 0-2 and relapsed/refractory disease were eligible, as well as patients who had not previously had systemic therapy but who were ineligible for standard curative chemotherapy regimens due to comorbid illness. We report on the first ten patients enrolled. The primary endpoint is response rate defined according to the 1999 Cheson criteria. RESULTS: Median age of participants was 56y (range, 42–76y), 9M, 1F. Histologies included PTCL not otherwise specified (n=4), angioimmunoblastic (n=4), cutaneous anaplastic large cell (n=1), hepatosplenic gamma/delta (n=1). 8 were relapsed, 2 previously untreated. 2 were refractory to their previous regimen. Median number of prior lines of systemic therapy is 1 (range, 0–3). Median number of cycles delivered to date, 2 (range: 1–8). Therapy has generally been well tolerated. 3 patients experienced grade 3–4 hematological toxicity, 3 experienced grade 3+ infectious complications and 1 had grade 3 rash. No thrombotic events have been seen to date. Best responses to date include 0 CR, 4 PR (2 angioimmunoblastic, 2 PTCL NOS), 1 SD (PTCL NOS), 2 PD (1 angioimmunoblastic, 1 PTCL NOS). Three deaths have occurred on study, due to disease progression (n=2) and pneumonia during cycle 1 (n=1, angioimmunoblastic). One patient has withdrawn from study post cycle 1 due to treatment related asthenia. One previously untreated patient still awaits the first response assessment; the overall response rate (CR+PR) to date in the remaining patients on an intent-to-treat basis is 4/9 (44%). 5 of 9 (56%) patients have achieved stable disease or better, for 2+, 3+, 5, 6 and 8+ months. For the two patients with previously refractory disease, best response was 1 PR for 6 months and 1 PD. CONCLUSION: Lenalidomide appears to be an active agent in the treatment of relapsed PTCL with an acceptable tolerability profile. Further recruitment and follow-up will allow us to better define the response rate, tolerability, TTP and OS with this regimen.

Safe and Effective Treatment of Patients with Peripheral T-Cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 253-253 ◽  
Author(s):  
Patrick B. Johnston ◽  
Amanda F. Cashen ◽  
Petros G. Nikolinakos ◽  
Anne W Beaven ◽  
Stefan Klaus Barta ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Anaplastic Lymphoma ◽  
Not Otherwise Specified ◽  
Baseline Characteristics ◽  
Grade 3

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis and repeated recurrence for most subtypes. Currently, anthracycline-based therapies such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or CHOP-like therapies are recommended as the first-line treatment for PTCL, but the prognosis remains poor with most patients relapsing within 5 years. Thus, improved treatment strategies are still needed. Belinostat is a potent, pan-histone deacetylase inhibitor that was recently approved in the United States for the treatment of patients with relapsed or refractory PTCL (R/R PTCL). Approval was based on results from the pivotal Phase 2 BELIEF study (O'Connor et al, JCO, 2015) of belinostat in R/R PTCL, which demonstrated durable clinical benefit (objective response rate [ORR] 25.8%) and tolerability. Since belinostat (Bel) and each of the components of the CHOP regimen target different aspects of the cell cycle with different mechanisms of action, there is potential for a synergistic effect of a Bel-CHOP combination treatment regimen for patients with PTCL. Methods: Patients with PTCL received CHOP in association with 1000 mg/m2 of belinostat on various schedules, repeated every 21-days for up to 6 cycles. The cohort schema followed a traditional "3+3" dose escalation design. The objective of Part A of the study was to determine the Maximum Tolerated Dose (MTD) of the Bel-CHOP combination. Once the MTD was determined, at least 10 more patients were to be treated in the Expansion Phase (Part B). Belinostat was to be administered as a 1000 mg/m2 IV infusion once daily for up to 5 days, depending on the assigned cohort (Fig 1). The starting cohort was Cohort 3 (CHOP + 1000 mg/m2 of daily belinostat on Days 1-3). Patients received primary prophylaxis with growth factor (G-CSF) support. Dose-limiting toxicities (DLT) were considered during the 1st cycle and included: non-hematological toxicity Grades 3-4, platelet count < 25 X 109/L at any time or ANC < 0.5 X 109/L lasting more than 7 days despite G-CSF administration. The primary endpoint of the study was the determination of the MTD of the Bel-CHOP combination. Secondary endpoints included safety, tolerability and ORR (complete response [CR] + partial response [PR]) and pharmacokinetics. Results: A total of 23 patients were enrolled in the study, 11 of which were treated in Part A. One patient in Part A was deemed inevaluable because the patient died due to disease progression before completing Cycle 1. The MTD was determined to be 1000 mg/m2 on Days 1-5 (Cohort 5); 12 more patients were then treated at this dose level (Part B). The only DLT experienced in the study was in Cohort 3 (Grade 3 Nausea and Vomiting). At the time of this abstract, 18/23 patients (78%) have completed all 6 cycles of Bel-CHOP, with 87% completing at least 4 cycles. Ten patients (43%) had at least one serious adverse event (SAE) and 18 (78%) had at least one Grade 3 or 4 adverse event (AE). The most frequent Grade 3/4 AEs were hematological in nature: neutrophil count decreased (26%), anemia (22%), neutropenia (17%) and white blood cell count decreased (17%). The ORR for the18 patients that have completed an End of Study Visit is 89% (16/18), with the vast majority achieving a CR [72% (n=13)], and 17% (n=3) a PR. Progressive disease was reported in 2 patients. Conclusions: These results demonstrate that the combination of belinostat with CHOP (Bel-CHOP) is well tolerated, with all components of CHOP and belinostat being given at their standard therapeutic doses. The rates of AEs were consistent with those typically reported with CHOP alone, and clinical activity was demonstrated with a response rate of 89% based on 18 evaluable patients. Thus, Bel-CHOP is a promising new regimen in PTCL that will be further tested in a Phase 3 randomized trial. Table. Table. Figure 1. Summary of Demographic and Baseline Characteristics AITL= angioimmunoblastic T-cell lymphoma; ALCL =anaplastic large-cell lymphoma; ALK = anaplastic lymphoma kinase; NOS = not otherwise specified Figure 1. Summary of Demographic and Baseline Characteristics. / AITL= angioimmunoblastic T-cell lymphoma; ALCL =anaplastic large-cell lymphoma; ALK = anaplastic lymphoma kinase; NOS = not otherwise specified Disclosures Barta: Seattle Genetics: Research Funding. Bhat:Spectrum Pharmaceuticals, Inc: Employment. Song:Spectrum Pharmaceutical, Inc: Employment. Choi:Apectrum Pharmaceuticals, Inc: Employment. Allen:Spectrum Pharmaceuticals, Inc: Employment. Foss:Spectrum Pharmaceuticals; Celgene: Seattle Genetics: Infinity; Millenium: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Pralatrexate in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results From the Pivotal PROPEL Study

2011 ◽  
Vol 29 (9) ◽  
pp. 1182-1189 ◽  
Author(s):  
Owen A. O'Connor ◽  
Barbara Pro ◽  
Lauren Pinter-Brown ◽  
Nancy Bartlett ◽  
Leslie Popplewell ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
International Workshop ◽  
Progression Free Survival ◽  
Median Number ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Prior Therapy

Purpose Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity. Patients and Methods Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m2/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS). Results Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%). Conclusion To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.

scholarly journals The Interim Efficacy of Epigenetic Priming Regimen with Azacytidine and Chidamide in Patients with Relapsed or Refractory Peripheral T Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2461-2461
Author(s):  
Kaiyang Ding ◽  
Xiao Shi ◽  
Haiyan Yang ◽  
Lei Cao ◽  
Xiaoli Zhao ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
T Cell Lymphoma ◽  
Combined Chemotherapy ◽  
Peripheral T Cell Lymphoma ◽  
Hematopoietic Stem

Abstract Introduction Peripheral T-cell lymphoma (PTCL) is a group of hematological malignancies originating from mature T/NK cells. Most of the subtypes are associated with aggressive clinical features and dismal outcomes. Routine first-line chemotherapy has low efficiency and a high recurrence rate, so there is an urgent need for new drugs. Monotherapy or combination therapy of epigenetic inhibitors have been shown to be effective in several hematologic malignancies. Here, we report the interim efficacy of an epigenetic priming regimen with azacytidine and chidamide prior to salvage chemotherapy for relapsed or refractory (R/R) PTCL. Methods The prospective phase II study (ChiCTR2000037232) enrolled pts were pathologically confirmed T/NK cell non-Hodgkin's lymphoma with at least one imaging measurable lesion. Pts needed to have received at least one systemic chemotherapy regimen including hematopoietic stem cell transplantation, radiotherapy, or a single epigenetic drug. Pts received AZA hypodermically at a dose of 100 mg on days 1 to 7, chidamide of 20 mg orally twice per week; the combined chemotherapy regimens included but were not limited to GemOx (gemcitabine, oxaliplatin); CPT (cyclophosphamide, prednisone, thalidomide) , etc. Treatment was performed for up to eight cycles of each 21 days. Pts who achieved partial response (PR) and better remission began maintenance therapy every two months with double epigenetic inhibitors for two years. The trial aimed to explore the efficacy and safety of AZA and chidamide combined chemotherapy in the treatment of R/R PTCL. The primary objective was investigator-assessed best overall response rate (ORR). Secondary objectives included duration of response (DOR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety profiles. Results A total of 24 pts have been enrolled, baseline characteristics are shown in Table 1. Pathological subtypes included angioimmunoblastic T-cell lymphoma（AITL, n=15）, PTCL-not otherwise specified (PTCL-NOS, n=4), extranodal NK/T-cell lymphoma (ENKTCL, n=3) and mycosis fungoides(MF, n=2). The median age was 57 (range,38-72) years with male predominance. Ann Arbor Classification ≥ stage III in 20 pts. Twelve pts had B symptoms at the time of diagnosis, five pts had performance status ≥ 3 before treatment. The median number of previous systemic treatment regimens was two. Autologous hematopoietic stem cell transplantation in two pts, radiation in three pts and prior treatments containing chidamide in eight pts. At the time of data cutoff, the median number of treatments for all pts was four cycles (range,1-13). Among 16 pts evaluable for response, the best ORR was 68.8% (11/16) with five pts achieved CR, six achieved PR. In subgroup analysis, eleven AITL pts achieved an objective response. The best ORR was 72.7% (8/11) with four pts attained CR, four attained PR (Table 2). The median follow-up was 12.4 (range, 0.1-18.7) months. For all pts, the median PFS was 6.7 months (95% CI,5.8-7.6), the median OS was 8.4 months (95% CI,0.0-18.3) (Figure 1). And the median DOR was 10.2 months (95% CI,4.9-15.5). For AITL pts, the median PFS was 14.6 months (95% CI,3.6-25.6), and the median OS was not reached (Figure 2). The OS between AITL and other subtypes pts was statistically significant (1-year OS: 76.2% vs 13.9%; p=0.003, Figure 3). Almost all pts had experienced at least one adverse event (AE). The most common grade 3 or 4 AEs were anemia, leukopenia, neutropenia, thrombocytopenia, and infections. Conclusions Epigenetic priming regimen with azacitidine plus chidamide with salvage chemotherapy is effective and tolerable. The best ORR of all enrolled pts with AITL were 68.8% and 72.7%, respectively. Compare to other subtypes, patients with AITL subtype benefit more obviously from our regimen with durable remission. And further studies will focus on patients with AITL and follicular helper T-cell originated. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphomas: Final Results from a Phase 1-2 Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4423-4423
Author(s):  
Jeremy S. Abramson ◽  
Eric D. Jacobsen ◽  
Robert Allyn Redd ◽  
Tak Takvorian ◽  
David C. Fisher ◽  
...  
Keyword(s):  
T Cell ◽  
Progressive Disease ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Median Number ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Grade 3

Abstract Background: Clofarabine is a second-generation purine analogue FDA-approved as an intravenous formulation for relapsed/refractory pediatric ALL. Purine analogues demonstrate significant clinical activity in non-Hodgkin lymphomas (NHL). Clofarabine may offer pharmacologic advantages over other nucleoside analogues including being a more efficient substrate for deoxycytidine kinase, more completely inhibiting ribonucleotide reductase and DNA polymerase α, and demonstrating improved activity in cells that are non-dividing or have a low proliferation rate. This phase 1-2 trial studied an oral formulation of clofarabine in relapsed or refractory NHL. Methods: Patients were eligible if they had relapsed or refractory NHL of any histologic subtype. All pts were required to have adequate organ function and performance status ≤2 as well as absence of CNS involvement. Patients were treated at 4 dose levels (1mg, 2mg, 4mg and ultimately 3mg) with oral clofarabine administered once daily on days 1-21 of a 28 day cycle for up to 6 cycles. Three to 6 pts were treated at each dose level in a traditional 3+3 design followed by a 10 patient dose expansion at the recommended phase 2 dose (RP2D). The phase 1 portion of this study has been published (Leuk Lymph 2013; 45:1915-1920). Phase 2 was designed to enroll 24 additional subjects. The primary endpoint in phase 2 was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. A total of 50 patients were accrued on the phase 1-2 trial; 31 subjects were treated in phase 1 and 19 in phase 2. Phase 2 accrual was stopped prematurely due to discontinuation of the drug formulation used in the study. All patients treated at the RP2D (n=36) are included in the phase 2 efficacy analysis since there were no differences in treatment or follow-up for these patients. Results: The median age for all patients was 69 years (range 45-92). Eighty-two percent had advanced stage at study entry. The median number of prior regimens was 2 (range 1-7) and 4 patients had prior auto stem cell transplant. Histologies included follicular lymphoma (FL, 13 pts), small lymphocytic lymphoma (SLL, 8 pts), diffuse large B-cell lymphoma (DLBCL, 6 pts), marginal zone lymphoma (MZL, 11 pts), mantle cell lymphoma (MCL, 9 pts), T-cell lymphoma (TCL, 2 pts) and lymphoplasmacytic lymphoma (LPL 1 pt). The 3mg dose was declared the RP2D, as previously reported. The most common toxicities were anemia (78%), leukopenia (66%), neutropenia (64%), thrombocytopenia (62%) and fatigue (60%). Twenty-nine patients (58%) experienced at least one grade 3-4 toxicity. The most common grade 3-4 toxicities were leukopenia and neutropenia (48%), thrombocytopenia (30%), anemia (14%) and fatigue (6%). There were 2 deaths on study, both considered unrelated to study drug (cardiac arrest, progressive disease). The median number of cycles administered was 4, and 18 patients (36%) completed all 6 cycles of therapy. The most common reasons for discontinuing therapy were progressive disease (34%) and toxicity (16%). Of 50 patients on study, the ORR was 28% (95% CI: 16 - 42%) with complete response rate (CRR) of 10% (95% CI: 3 - 22%). An additional 36% had stable disease (SD). By histology, responses were seen in 5/11 MZL, 4/9 MCL, 3/8 SLL, 3/13 FL, and 1/1 LPL. No responses were observed in DLBCL or TCL, although an angioimmunoblastic T-cell lymphoma patient had SD with a 42% reduction in tumor volume, and a mycosis fungoides patient had significant reduction in cutaneous disease burden. Among 36 patients treated at the RP2D and included in the phase 2 analysis, the ORR was 28% (95% CI: 14 - 45%) with CRR of 8% (95% CI: 2 - 22%), and 44% of patients with SD. A higher proportion of patients treated at a non-RP2D experienced progressive disease on study (43% vs. 28% in the RP2D cohort). The median PFS was 5.5 months, and the one- and two- year PFS were 32% (95% CI: 20%, 45%) and 16% (95% CI: 7.5%, 27%), respectively. The median duration of follow-up was 3.8 years, with 26 patients alive and 22 deceased at last follow-up; two patients were lost to follow-up. The median OS was not reached, and the 3 year OS was 58% (95% CI: 43%, 71%). Conclusion: Oral clofarabine is generally well tolerated and produces disease control in a substantial proportion of patients with relapsed/refractory NHL, particularly in indolent histologies and MCL. Disclosures Abramson: Sanofi: Consultancy. Off Label Use: Clofarabine is not FDA-approved for non-Hodgkin lymphoma. Brown:Sanofi: Consultancy.

scholarly journals Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick B. Johnston ◽  
Amanda F. Cashen ◽  
Petros G. Nikolinakos ◽  
Anne W. Beaven ◽  
Stefan Klaus Barta ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Peripheral T Cell Lymphoma ◽  
Grade 3

Abstract Background Belinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK). Methods Patients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose. Results Twenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1–3 schedule, resulting in escalation to Day 1–5 schedule (n = 3). No DLTs were observed and Day 1–5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent. Conclusions Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT01839097.

Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy

2012 ◽  
Vol 30 (6) ◽  
pp. 631-636 ◽  
Author(s):  
Bertrand Coiffier ◽  
Barbara Pro ◽  
H. Miles Prince ◽  
Francine Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Prior Systemic Therapy

Purpose Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients and Methods Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee. Results Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%). Conclusion Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.

Low Absolute Lymphocyte Count Predicts Chemotherapy Response and Survival In Peripheral T-Cell Lymphoma, NOS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3135-3135
Author(s):  
Yu Ri Kim ◽  
yun Deok Kim ◽  
Jin Seok Kim ◽  
June-Won Cheong ◽  
soo Jeong Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Factor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Independent Prognostic Factor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Overall Response

Abstract Abstract 3135 Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS) is heterogenous groups of aggressive T-cell lymphoma and treatment outcome is dismal. Lymphopenia is an independent prognostic factor for survival for B-cell lymphoma. The ALC at diagnosis on survival in T-cell lymphoma has not been studied. Thus, we studied the role of ALC at diagnosis on clinical outcome in patients with PTCL, NOS. Between 2001 and 2009, 32 patients with PTCL, NOS reviewed for the study. Median patient age was 57 (range 34–78) years. Median ALC at the time of diagnosis was 1.54 (range 0.41–12.64×109/L). Patients were divided two groups according to ALC count 1.0 ×109/L. Ten patients (31%) had lower ALC at diagnosis. Median follow up duration was 299 days (range 11–2164 days). Overall response rate was 61.5% (16 of 26 patients) and complete response (CR) rate was 42% (11 of 26 patients). Only two patients reached CR in low ALC group.There was no significant difference in overall response rate because of small number of patients. Superior overall survival was observed with an ALC 1.0 × 109/L (N = 22) versus an ALC < 1.0 × 109/L (N=10) (median OS: not reached vs 242 days, OS rates at 5 years, 57% vs 0%, p =0.016, respectively). Multivariate analysis demonstrated ALC to be an independent prognostic indicator for OS (Hazard Ratio 3.5, 95% confidence intervals 1.2–10.2; p<0.019) when compared to the International prognostic index (IPI) and Prognostic Index for PTCLU (PIT). This study suggested that low ALC is an independent prognostic factor for survival in patients with PTCL, NOS. Disclosures: No relevant conflicts of interest to declare.

Cutaneous Toxicity Associated with Pralatrexate in Cutaneous and Peripheral T-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3660-3660 ◽  
Author(s):  
Terri L. Parker ◽  
Lisa Barbarotta ◽  
Michael Girardi ◽  
Francine M. Foss
Keyword(s):  
Adverse Event ◽  
Data Analysis ◽  
T Cell ◽  
Cell Lymphoma ◽  
Median Number ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Cutaneous Toxicity ◽  
Off Label

Abstract Abstract 3660 Background: Pralatrexate is a folate analogue metabolic inhibitor that is approved for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) (O'Connor, O.A. et al. JCO. 2011 29: 1181–1189). More recently, pralatrexate has been investigated for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) (Horowitz, S.M. et al. Blood. 2012 119: 4115–4122). The most common adverse event (AE) observed with pralatrexate has been mucositis with other reported AEs consisting of fatigue, nausea, and cutaneous toxicity. Methods: We retrospectively analyzed the data of 22 patients who had received pralatrexate for a diagnosis of either PTCL or CTCL at our institution since 2010 in order to determine the incidence of cutaneous toxicity. Results: Of the 22 patients, 4 had a diagnosis of PTCL, 18 had CTCL. In the PTCL cohort, the median age was 66.5 with the median number of prior treatments (nonsystemic and systemic) being 2.75. One patient (25%) developed cutaneous toxicity which resulted in death. A skin biopsy revealed toxic erythema of chemotherapy and the skin lesions progressed to bullae and moist desquamation. In the CTCL cohort, the median age was 60 with the median number of treatments being 5. A total of 14 patients (78%) developed cutaneous toxicity. The toxicity included worsening erythema, skin breakdown, ulceration, and pain at the CTCL lesion sites. The majority of patients (n= 10; 71%) developed the toxicity following cycle 1 week 1 of treatment. The development of cutaneous toxicity was seen in 8 patients at a dose of 15mg/m2, in 3 patients at a dose of 10mg/m2, and in 2 patients who underwent dose escalations to 17.5mg/m2 and 20mg/m2respectively. Of those patients who developed cutaneous toxicity, 8 (57%) required the pralatrexate to be held and 2 patients (14%) required hospitalization and treatment with intravenous antibiotics for superimposed skin infection. The cutaneous toxicity observed was not associated with any other adverse event. Seven patients (39%) in the entire CTCL cohort developed grade I/II mucositis and 3 (17%) developed grade I diarrhea. In 7 patients (50%) the pralatrexate was restarted at a lower dose, 3 patients were changed to an every other week dosing schedule, and 2 patients continued on pralatrexate with no change following resolution of their symptoms. Only 2 patients were not continued on pralatrexate following the cutaneous toxicity. In all 12 patients who were retreated with pralatrexate, cutaneous toxicity did not reoccur and the dose was able to be escalated. At the time of data analysis, 7 patients remained on treatment with pralatrexate while the remainder had discontinued therapy secondary to disease progression. Conclusions: In this retrospective review, a high incidence of cutaneous toxicity was seen in CTCL patients who were treated with pralatrexate. The cutaneous toxicity might be interpreted as a “skin flare” since it may be concentrated at sites of CTCL lesions. The majority of patients developed the toxicity with the first dose and were able to continue on pralatrexate at a lower dose with eventual dose escalation. Based on data analysis, the “skin flare” is not dose dependent or associated with disease response. Disclosures: Off Label Use: Pralatrexate is FDA approved for the treatment of relapsed or refractory peripheral T-cell lymphoma. Our abstract discusses its use, specifically the cutaneous toxicity observed, in both peripheral and cutaneous T-cell lymphoma. The use of pralatrexate in relapsed or refractory cutaneous T-cell lymphoma is off-label. Barbarotta:Genentech: Speakers Bureau; Allos: Speakers Bureau. Foss:Seattle Genetics: Consultancy; Celgene: Consultancy; Eisai: Consultancy; Celgene: Study Grant, Study Grant Other; Merck: Study Grant, Study Grant Other; Allos: Consultancy.

Outcomes of GDPT (gemcitabine, cisplatin, prednisone,thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8018-8018
Author(s):  
Ling Li ◽  
Yuanyuan Sun ◽  
Xin Li ◽  
Lei Zhang ◽  
Xinhua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
The Other ◽  
Newly Diagnosed ◽  
Peripheral T Cell Lymphoma ◽  
Significant Difference ◽  
Gene Expression Levels

8018 Background: Peripheral T-cell lymphoma(PTCL) is highly heterogeneous invasive NHL.There is no consensus standard treatment for it now. So outcomes of GDPT versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL were compared. Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT group (77 cases) and CHOP group (76 cases). Patients in each group were further divided into four subgroups: PTCL-NOS, ALCL, AITL, and an other types, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3 and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, PFS and OS were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The ORR of the GDPT group was better than that of the CHOP group (66.3%vs. 50.0%, P= 0.042), as was the CR rate (42.9% vs. 27.6%, P= 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% vs. 53.0% for PFS, P= 0.035; 66.8% vs. 53.6% for OS, P= 0.039).In the GDPT group, the difference in CR between the four subgroups was statistically significant (P = 0.046).In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( P= < 0.001 and P= 0.005, respectively).There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup( P= 0.015; P= 0.003; P= 0.005, respectively).The data also showed a significant difference in OS among the four subgroups within the GDPT group ( P= 0.001).The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( P= 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3 and TOP2A. Conclusions: The GDPT group had better response rates and prolonged the patients’ PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Clinical trial information: NCT01664975 .

scholarly journals The Combination of Bortezomib with Cyclophosphamide, Epirubicin, Etoposide and Prednisone (BCHEP) Regimen As First-Line Treatment for Untreated Patients with Peripheral T Cell Lymphoma: A Prospective, Single Arm, Phase II Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2482-2482
Author(s):  
Haiyan Yang ◽  
Cong Li
Keyword(s):  
T Cell ◽  
Interim Analysis ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
First Line ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
First Line Treatment

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a clinically and biologically heterogeneous disease with poor prognosis. The response rate of standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) is only 50-60%, with a poor long-term survival rate of 10-30%. The addition of etoposide to CHOP increases response rate, but not progression free survival (PFS) or overall survival (OS). Recent study reported that nuclear factor kappa B (NF-κB) pathway plays a critical role in PTCL. Bortezomib, a potent and reversible proteasome inhibitor, can induce tumor cell apoptosis by inhibiting activation of NF-κB pathway and has been recommended as single agent option in relapse/refractory PTCL. We aimed to study the efficacy and safety of bortezomib in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BCHEP) in newly diagnosed PTCL patients for the first time. METHODS: A prospective, single arm, phase 2 study was conducted (NCT04061772). This is an interim analysis. Patients with newly diagnosis of PTCL were treated with up to 6 cycles of BCHEP regimen every 3 weeks. Bortezomib was subcutaneously administered on Days 1 and 8 at a dose of 1.3 mg/m 2 in combination with CHEP， consisting of 100 mg/m 2 etoposide on Days 1 to 3, 750mg/m 2 cyclophosphamide on Day 1, 75mg/m 2 epirubicin on Day 1 and 100mg prednisone on Days 1 to 5. The primary endpoint of the study was ORR including complete response (CR) and partial response (PR). The secondary endpoints included progression free survival (PFS), overall survival (OS) and adverse events (AEs). RESULTS: Between February 2019 and January 2021, a total of twenty-six patients were enrolled. Median age was 57 years (range 37-69) and six (23.1%) were female. Pathological subtypes included ALK-positive anaplastic cell lymphoma (ALCL, n=2), ALK-negative ALCL (n=4), PTCL, not otherwise specified (PTCL-NOS, n=9) and angioimmunoblastic T-cell lymphoma (AITL, n=11). Nineteen patients had stage III/IV disease and eleven had B symptoms, including weight loss in three cases and fever in eight. Ten patients had elevated serum lactate dehydrogenase (LDH), eleven had IPI score higher than 2. All patients had completed BCHEP treatment for at least two cycles and received imaging evaluation. Ten patients received prophylaxis of intrathecal chemotherapy with methotrexate at least once. Three patients received consolidated radiotherapy for metabolic residuals after chemotherapy, while one received autologous hematopoietic stem cell transplantation as consolidation treatment. This study had reached the primary end point at this interim analysis. The ORR was 92.3% (24/26) with a CR rate of 57.7% (15/26). Two patients had progression of disease within two cycles of chemotherapy. After a median follow-up of 16.3 months, twelve patients had disease progression, and six died. Median PFS was 10.9 months and 1-year PFS rate was 65.4%. Median OS was 14.6 months and 1-year OS rate was 88.5%. No patient presented with Grade 5 AE. The most frequent all-grade hematological toxicity was leucopenia (42.3%,11/26), anemia (50%,13/26) and thrombocytopenia (23.1%, 6/26). Other common toxicity included intestinal infection or pneumonia (19.2%, 5/26), Grade 1 peripheral neuropathy (15.4%, 4/26) and nausea (7.7%, 2/26). Dose reduction was performed in eight patients. CONCLUSIONS: Interim results showed that bortezomib in combination with CHEP is associated with high response rate and manageable toxicity in patients with previously untreated PTCL. The BCHEP regimen may serve as a novel first-line treatment option for patients with PTCL. The study is going on to enroll patients and updating results, including the prognostic value of serum inflammatory factors. Larger trials will be necessary to further verify the efficacy of this regimen in treatment naïve PTCL patients and to overcome relapse after remission. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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