scholarly journals Efficacy and Safety of Dose Attenuated CHOP Chemotherapy for Peripheral T-Cell Lymphoma in Elderly Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3953-3953 ◽  
Author(s):  
Eun-Ji Choi ◽  
Dok Hyun Yoon ◽  
Chan-Sik Park ◽  
Jooryung Huh ◽  
Sang-wook Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Dose Reduction ◽  
Cell Lymphoma ◽  
Performance Status ◽  
The Elderly ◽  
T Cell Lymphoma ◽  
Free Survival ◽  
Full Dose ◽  
Grade 3

Abstract Background Peripheral T-cell lymphoma (PTCL) is an uncommon disease entity that accounts for 10-15% of all non-Hodgkin lymphomas (NHL). Except for anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the median age of patients ranges between 5th to 6th decades of life. Unfortunately, substantial numbers of the elderly patients are unable to tolerate full dose chemotherapy due to comorbidities or poor functional status. In this respect, we aimed to evaluate the efficacy and safety of the dose attenuated CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy in the elderly PTCL patients. Methods We analyzed data from patients with newly diagnosed PTCL aged over 65 years who presented to our institute between April 2001 and December 2014. NK/T cell lymphoma and mycosis fungoides were excluded from the study. Forty three patients were treated with the dose attenuated CHOP, which is a combination of cyclophosphamide (562.5 mg/m2 for 1 day, 25% dose reduction from full dose), doxorubicin (37.5 mg/m2 for 1 day, 25% dose reduction from full dose), vincristine (1.4 mg/m2 for 1 day) and prednisolone (50 mg bid for 5 days). Results The median age was 72 years (range 65-86). Among the forty three patients, PTCL-not otherwise specified (NOS) accounted for 62.8% (n=27), AITL for 16.3% (n=7), ALK-negative ALCL for 11.6% (n=5), and enteropathy-associated T cell lymphoma (EATL) for 9.3% (n=4), respectively. Although 79.1% (n=34) of patients had good performance status (Eastern Cooperative Oncology Group (ECOG) performance status <2), 93.0% (n=40) were in advanced stage (> Ann Arbor stage II). The overall response rate (ORR) and complete response (CR) rate was 77.8% and 52.8%, respectively. With a median follow-up period of 50.1 months (range 16.4-83.8), the 5-year event-free survival (EFS) and overall survival (OS) was 31.1% and 45.1%. The 5-year relapse-free survival (RFS) in those who achieved CR was 57.4%. Involvement of extranodal sites (≥2) (P=0.007 and hazard ratio [HR] 1.76 for OS, P=0.026 and HR 2.09 for EFS) was an independent prognostic factor for both EFS and OS. The grade 3 and 4 adverse events were consistent with the expected toxic effects of CHOP chemotherapy. Grade 3 or 4 neutropenia and thrombocytopenia was observed in 71.4% and 19.0%, respectively. However, 45.2% experienced febrile neutropenia. In addition, twelve patients died from treatment-related toxicities. Another 10 died from progression of disease, and the other two from unknown causes. Conclusion Dose attenuated CHOP with 25% dose reduction of cyclophosphamide and doxorubicin for elderly PTCL doesn't seem to diminish response or survival rates, which resulted in at least comparable efficacy outcomes to the prior reports (J Clin Oncol 2008;26:4124-4130). However, it is still associated with significant toxicities with high treatment-related mortalities. Novel treatment strategies for these vulnerable elderly patients are urgently needed. Disclosures No relevant conflicts of interest to declare.

Pralatrexate Is Active in Cutaneous T-Cell Lymphoma (CTCL): Results of a Multicenter, Dose-Finding Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 919-919
Author(s):  
Steven M. Horwitz ◽  
Madeleine Duvic ◽  
Youn Kim ◽  
Jasmine M Zain ◽  
Mary Jo Lechowicz ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Dose Reduction ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Single Agent ◽  
Optimal Dose ◽  
T Cell Lymphoma ◽  
Grade 3

Abstract Abstract 919 Background: Pralatrexate enters cancer cells via the reduced folate carrier-1 (RFC-1) and is efficiently polyglutamated by folylpolyglutamyl synthetase (FPGS), leading to high intracellular retention. In a Phase 1/2 study of patients with hematologic malignancies, pralatrexate demonstrated activity in aggressive T-cell lymphoma with a maximum tolerated dose (MTD) of 30 mg/m2 once weekly for 6 of 7 weeks. The generally indolent course of CTCL may be better treated at lower doses in a maintenance fashion if a lower incidence and severity of adverse events can be achieved while preserving activity. PDX-010 is an open-label, single-agent, multicenter, Phase 1 dose-reduction trial in patients with relapsed or refractory CTCL. The primary objective is to identify an optimal dose and schedule of pralatrexate for these patients. Methods: Eligibility included mycosis fungoides (MF), Sézary syndrome (SS), and primary cutaneous anaplastic large cell lymphoma (ALCL); with disease progression after at least 1 prior systemic therapy. The pralatrexate dose and schedule started at 30 mg/m2 by IV push on 3 of 4 weeks and subsequent cohorts received reduced doses (20, 15, 10 mg/m2) and/or schedules (3/4 or 2/3 weeks) of pralatrexate based on tolerability. All patients received supplementation with vitamin B12 1 mg intramuscularly every 8-10 weeks and folic acid 1 mg orally once daily. As we sought a well tolerated regimen the definition of DLTs to trigger dose reduction included toxicities such as grade ≥ 3 neutropenia, grade ≥ 2 thrombocytopenia, febrile neutropenia, grade ≥ 2 mucositis/stomatitis, and any toxicity leading to dose omission or reduction in cycle 1. If DLT occurred and a response was seen, the following cohort was opened at the next lower dose or next less frequent schedule. Response was evaluated by modified severity-weighted adjustment tool (SWAT) every 2 cycles for 6 months and then every 4 cycles. For patients with lymph node involvement, scans were completed at baseline and upon clinical response or end of treatment, whichever occurred first. Results: Thirty-one patients received pralatrexate, with 18 (58%) men and median age of 57 yrs (range, 30-81). Patients had received a median of 6 prior therapies (range, 1-25). Cohorts at the following doses/schedules were enrolled: 30 mg/m2 x 3/4 weeks (n=2), 20 mg/m2 x 3/4 weeks (n=3), 20 mg/m2 x 2/3 weeks (n=7), 15 mg/m2 x 3/4 weeks (n=6), 15 mg/m2 x 2/3 weeks (n=3), and 10 mg/m2 x 3/4 weeks (n=10). Patients received pralatrexate for a median of 72 days (range, 7-491+); 4 patients received >10 cycles of treatment. The most common treatment-related adverse events (all grades) were mucositis (18 patients [58%]), nausea (14 patients [45%]), fatigue (14 patients [45%]), pyrexia (7 patients [23%]), vomiting (6 patients [19%]), anemia (6 patients [19%]), and edema (5 patients [16%]). Grade 3-4 treatment-related toxicities in >1 patient each were mucositis (4 patients [13%]) and anemia (2 patients [6%]). Mucositis was dose limiting (≥ grade 2) in 8 patients (26%). A total of 11 responses were observed, including 2 complete responses and 9 partial responses. In the 18 patients who received pralatrexate at a dose intensity of 15 mg/m2 x 3/4 weeks or greater, the objective response rate was 56% (10/18 patients). This appeared to be the threshold dose for substantial activity in CTCL, below which the incidence of responses decreased in this dose de-escalation trial. Conclusion: Pralatrexate shows impressive activity in the treatment of relapsed CTCL. The optimal dose and schedule that provided activity with tolerability for CTCL was determined to be pralatrexate 15 mg/m2 weekly on 3 of 4 weeks. This cohort is being expanded to better assess efficacy and durability. Disclosures: Horwitz: Allos Therapeutics, Inc: Consultancy, Research Funding. Duvic:Allos Therapeutics, Inc.: Research Funding. Lechowicz:Allos Therapeutics, Inc.: Consultancy. Fruchtman:Allos Therapeutics, Inc.: Employment.

scholarly journals A Dose Escalation Study of RP6530, a Novel Dual PI3K δ/γ Inhibitor, in Patients with Relapsed/Refractory T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3004-3004 ◽  
Author(s):  
Yasuhiro Oki ◽  
Auris Huen ◽  
Prajak J Barde ◽  
Kumar Penmetsa ◽  
Alda Ashu ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Dose Escalation ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Performance Status ◽  
T Cell Lymphoma ◽  
Clinical Activity ◽  
Dose Escalation Study ◽  
Grade 3

Abstract Introduction: The δ isoform of PI3K is highly expressed in cells of hematopoietic origin. The γ isoform is associated with T-lymphocytes and neutrophils and plays a distinct role in T-cell function. Since δ/γ isoforms are synergistic in the growth and survival of certain T-cell malignancies, dual targeting of PI3K δ/γ is an attractive intervention strategy in patients with T-cell lymphoma. RP6530 is a novel, highly specific dual PI3K δ/γ inhibitor with nanomolar inhibitory potency for both isotypes. It has shown acceptable safety profile and efficacy in patients (pts) with advanced hematologic malignancies in a Phase 1 study (ASH 2015). Herein, we present the preliminary results from an ongoing Phase 1/1b, dose escalation study of RP6530 in 11 pts with mature T-cell neoplasms (NCT02567656). Methods: The study consists of dose escalation cohorts to determine the MTD of RP6530 using a standard 3+3 design, followed by two expansion cohorts enrolling 20 pts with peripheral T-cell lymphoma (PTCL) and 20 pts with cutaneous T-cell lymphoma (CTCL). Pts with a diagnosis of PTCL or CTCL who have received at least one prior systemic therapy, ECOG performance status ≤ 2 and measurable/evaluable disease are eligible. This study evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and clinical activity of RP6530 administered twice daily (BID) in 28-day cycles. Responses were evaluated for PTCL and CTCL based on IWG criteria (Cheson 2014) and the modified Severity Weighted Assessment Tool (mSWAT) respectively. Dose limiting toxicity (DLT) was defined by a toxicity of grade 3/4 that is considered related to treatment during the first cycle of treatment. Results: To date eleven pts (6 PTCL and 5 CTCL) (5 males and six females) have been enrolled at three dose levels: 200 mg BID, 400 mg BID and 800 mg BID. ECOG performance status score was 0/1/2 in 10/1/0 pts, respectively, with a mean age of 68 yrs (range 52-76). Pts had a median of 3 (range: 3-6) prior treatment regimens, and 5 pts had refractory disease and 6 relapsed on prior treatments. RP6530 was well tolerated without any DLT or related serious adverse event reported to date. A total of 52 non-serious adverse events were reported: 41 Grade 1/2 and 11 Grade 3/4. The most common adverse events included mild vomiting (18%), diarrhoea (18%), fatigue (18%), and rash (18%). No Grade 3/4 adverse events were deemed related to RP6530 except for ALT/AST elevation in one pt. No pt discontinued treatment due to a safety issue. Dose-proportional increases in plasma concentrations were observed in PKs. Dose escalation is currently ongoing at 800 mg BID. Five pts were evaluated for responses at Cycle 3, Day1. Two pts (1 PTCL and 1 CTCL) experienced PR (40%) that are ongoing >5 months, and three pts experienced stable disease lasting for >3 months (60%). Three pts experienced rapid disease progression during first cycle, and discontinued treatment prematurely. Conclusion: This ongoing study of RP6530 demonstrated an acceptable safety profile at doses evaluated, with a promising clinical activity. The results support further evaluation of RP6530 in pts with mature T-cell neoplasms. Disclosures Oki: Novartis: Research Funding. Barde:Rhizen Pharmaceuticals SA: Employment. Penmetsa:Rhizen Pharmaceuticals SA: Employment. Viswanadha:Incozen Therapeutics: Employment.

T-CELL LYMPHOMA IN THE ELDERLY PATIENTS. WHO IS YOUNG, OLD, AND ELDERLY?

2019 ◽  
Vol 37 ◽  
pp. 465-467
Author(s):  
A. Janikova ◽  
R. Chloupkova ◽  
P. Klener ◽  
K. Benesova ◽  
V. Campr ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Cell Lymphoma ◽  
The Elderly ◽  
T Cell Lymphoma ◽  
Young Old

Phase II Study of Proteasome Inhibitor Bortezomib (Velcade®) in Patients with Relapsed/Refractory T-Cell Lymphoma: Preliminary Results.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2462-2462 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Monica Tani ◽  
Gerardo Musuraca ◽  
Vittorio Stefoni ◽  
Enrica Marchi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Single Agent ◽  
Safety Data ◽  
T Cell Lymphoma ◽  
Skin Involvement ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Grade 3

Abstract The mechanisms by which Bortezomib elicits its antitumor activity may vary among tumor types, and the extent to which each affected pathway is critical to the inhibition of tumor growth could also differ. The aim of this study was to determine the efficacy and toxicity of Bortezomib in previously pretreated patients with peripheral T-cell lymphoma unspecified (PTCLU) with only skin involvement and cutaneous T-cell lymphomas (CTCL). Eligibility criteria included PTCLU or CTCL (according to REAL/WHO classification) with measurable disease; any stage, any IPI, any bone marrow status; second or more relapse or refractory disease; age ≥18; ECOG performance status ≤ 2; Hb ≥10 g/dL, ANC ≥ 1.5x109/L and platelets ≥ 100 × 109/L; normal hepatic, renal and cardiac functions; and voluntary written informed consent. Bortezomib was given at 1.3 mg/m2 IV push on days 1, 4, 8 and 11 every 21 days. Restaging was done every 2 cycles. Patients were treated for up to a total of 6 cycles unless removed from study for failure to respond or toxicity. The response criteria were those recommended by NCI sponsored Working Group. At data reporting for this abstract, 15 patients were enrolled and 12 were evaluable for response. Of these 12 patients, 10 had CTCL and 2 PTCL; 11 were male and 1 female; 6 were aged >60 years (range 48–80). Overall response rate was 67% (2 CR + 6 PR) and the remaining 4 patients had PD. Histologically the responder patients were 7 CTCL and 1 PTCL. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 5 patients. The most common grade ≥ 3 AEs were neutropenia, thrombocytopenia and peripheral neuropathy. These preliminary data indicate that Bortezomib is active as a single agent for patients with relapsed/refractory CTCL and PTCL with skin involvement. Final efficacy and safety data will be presented.

Final result of phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for elderly patients with small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8054-8054
Author(s):  
O. Ishimoto ◽  
A. Inoue ◽  
S. Sugawara ◽  
M. Harada ◽  
K. Usui ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Elderly Population ◽  
Overall Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
The Elderly ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3

8054 Background: AMR, a new anthracycline agent, is active for SCLC. We had previously reported a phase I study of AMR combined with CBDCA for elderly patients with SCLC (J Thorac Oncol 1:551, 2006). The objective of this study is to evaluate the efficacy and the safety of this combination for elderly patients with SCLC. Methods: Chemotherapy naïve elderly patients (70 years or older) with SCLC received AMR (35 mg/m2, day1–3) and CBDCA (AUC 4.0, day1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 60% in eligible pts would indicate potential usefulness while ORR of 40% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, the estimated accrual was 30 patients. Results: From January 2005 to November 2007, 36 pts were enrolled from 11 institutions. Patient characteristics were: Male/Female 27/9; median age 76 (range 70–83); Performance status 0/1 17/19. The median numbers of treatment cycles were 4 (range 2–7). The objective responses were CR 1, PR 31, SD 2, PD 2, and the ORR was 89%. Median PFS was 5.8 months and median survival time was 18.6 months. Grade 3–4 neutropenia was observed in all the patients and 5 patients (14%) suffered from grade 3–4 febrile neutropenia. Other toxicities were moderate and no treatment related death was observed. Conclusions: AMR combined with CBDCA is quite effective for SCLC with acceptable toxicities even for the elderly population. Further evaluation of this regimen is warranted. No significant financial relationships to disclose.

scholarly journals RT-DeVIC Therapy Is Effective for Localized NK/T Cell Lymphoma Patiens

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1702-1702 ◽  
Author(s):  
Kyoko Ueda ◽  
Noriko Nishimura ◽  
Yuko Mishima ◽  
Hideaki Nitta ◽  
Yoshiharu Kusano ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
T Cell ◽  
Local Control ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
Free Survival ◽  
Nk T Cell ◽  
Grade 3

Abstract BACKGROUNDS: Extranodal natural killer (NK) /T cell lymphoma, nasal type is much common in East Asia than in Western countries. CHOP therapy is not effective for NK/T cell lymphoma because of the drug resistance induced by P glycoprotein. Yamaguchi et al reported the effectiveness of concurrent radiotherapy and DeVIC (RT-DeVIC) therapy for localized nasal NK/T cell lymphoma. Nowadays, RT-DeVIC therapy is recognized as a standard treatment. So far, we have limited information about this treatment because NK/T cell lymphoma is rare phenotype. PATIENTS AND METHODS: We reviewed retrospectively the patients with localized NK/T cell lymphoma treated with RT-DeVIC therapy. Radiation therapy was administered for a total dose of 50 Gy. Concurrently, chemotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) was performed up to 3 cycles. The primary objectives of this analysis were to evaluate the response rates and progression free survival (PFS) and overall survival (OS). RESULTS: A total of 20 patients who diagnosed as nasal NK/T cell lymphoma between April 2007 and October 2012 were analyzed. Sixteen patients were stage 1E and 4 were Stage 2E. As the NK/T cell lymphoma prognostic index, 6 patients were group 1, 10 were group 2, 3 were group 3, and 1 was group 4. Seventeen patients completed 3 cycles of DeVIC therapy and 19 patients completed planned radiation therapy. Overall response rate (ORR) was 75% and CR rate was 70% in the entire patients. Local control was 90%. Half of the patients who reached CR showed long time survival without disease progression. On the other hand, 7 of 14 patients relapsed after CR, and all 5 patients experienced systemic failure. The sites of relapse were paranasal sinuses (n=2), skin (n=3), brain (n=1), testis (n=1). Among them, one patient reached 2nd CR. However, 5 patients were not eligible for salvage chemotherapy, because lymphoma progressed rapidly and their general condition became worse. Six patients did not reach CR after RT-DeVIC therapy. Five of them experienced systemic relapse and median survival of them was only 8 months. The median follow up time was 17.6 months (range 2 – 77.9 months). Median overall survival was not reached and median progression free survival was 14.6 months. Risk factors predicted of OS or PFS were not clear. All entire patients experienced grade 3 or 4 neutropenia. Mucositis was common non-hematological toxicity and it was the major cause of grade 3 or 4 appetite loss. Only one patient discontinued RT-DeVIC due to grade 3 mucositis, grade 3 dermatitis and septic shock. CONCLUSION: We reviewed treatment outcomes of 20 cases of RT-DeVIC therapy. In this analysis, the majority of relapsed or refractory cases showed systemic disease and the prognosis of these patients were poor. However, RT-DeVIC therapy showed excellent local control and response rates which were similar to the prior study. The effectiveness of RT-DeVIC therapy for patients with NK/T cell lymphoma was reconfirmed. Disclosures No relevant conflicts of interest to declare.

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.

TCL-386: Patterns of Care for Elderly Patients with Peripheral T-Cell Lymphoma: A Report from the International T-Cell Project 1.0

2021 ◽  
Vol 21 ◽  
pp. S415
Author(s):  
Tetiana Skrypets ◽  
Monica Civallero ◽  
Martina Manni ◽  
Julie Marie Vose ◽  
Ivan Dlouhy ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Patterns Of Care ◽  
Peripheral T Cell Lymphoma
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