scholarly journals A Phase Ib Study of Linperlisib in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1386-1386
Author(s):  
Jie Jin ◽  
Hong Cen ◽  
Keshu Zhou ◽  
Xiaohong Xu ◽  
Fei Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
B Cell ◽  
Disease Progression ◽  
Safety Profile ◽  
Cell Lymphoma ◽  
Phase 2 ◽  
Oral Agent ◽  
Peripheral T Cell Lymphoma ◽  
Phase 1B

Abstract Introduction Peripheral T cell lymphoma (PTCL) is an aggressive tumor type with poor survival, where treatment options for relapsed and/or refractory (r/r) disease are very limited. Standard treatments have a median progression free survival (PFS) of only 3-4 months. PI3K inhibitors, blocking tumor cell proliferation, survival, migration, and modulating multiple functions on the tumor microenvironment have previously shown to be active in T cell lymphomas, as well as B-cell lymphomas and chronic lymphocytic leukemia. However, the use of these agents has been hampered by tolerability issues, including toxicities such as diarrhea, colitis, hepatotoxicity, pneumonitis, hyperglycemia, and rash. The PI3Kδ selective inhibitor, linperlisib, is a structurally novel oral agent that has been demonstrated to be clinically efficacious with a favorable safety profile in Phase 1 and Phase 2 trials in B-cell malignancies previously. Here we report updated clinical data with longer follow-up from a Phase 1b clinical trial of linperlisib monotherapy in relapsed or refractory PTCL. Methods The Phase 1b PTCL clinical trial (NCT04108325) was conducted at 10 sites in China. There were 43 patients (pts) with different PTCL histologies enrolled in the study, including PTCL-NOS (17 pts), AITL (16 pts), ALCL (6 pts), NKT (3 pts), and MEITL (1 pt). Tumor assessments are performed every two treatment cycles with 28 days as one treatment cycle using IWG 2007 criteria. Safety was evaluated according to CTCAE v5.0. Linperlisib was dosed at 80 mg QD (RP2D) orally until disease progression, intolerable toxicity or withdrawal from the study. Results In the Phase 1b study of linperlisib monotherapy in r/r PTCL, as of a date cut-off of July 22, 2021, there were 43 pts enrolled with a median age of 58 years, ECOG 0-1 (41 pts, 95.3%), Stage III or IV (39 pts, 90.7%). The pts had a median of 2 prior systemic therapies, and 36 pts (83.7%) were refractory to their last treatment. The majority (83.7%) of pts had prior CHOP or CHOP-like therapy. Thirty-eight out of 43 pts (88.4%) experienced a treatment related adverse event (TRAE), majority (90.3%) of AEs were Grade 1 or Grade 2. The most common TRAEs (≥10%) were neutropenia (60.5%), leukopenia (37.2%), hypertriglyceridemia (37.2%), hypercholesterolemia (32.6%), AST increase (20.9%), ALT increase (23.3%), pneumonia (16.3%), anemia (16.3%), gamma glutamyl transpeptidase increase (16.3%), thrombocytopenia (14.0%), alkaline phosphatase increase (14.0%) and lymphocyte count increase (11.6%). The observed safety profile of linperlisib in r/r PTCL is similar to that observed in r/r follicular lymphoma, with no new toxicities reported. The Grade 3 and above AE occurring in >5% of pts was neutropenia (16.3%). Three pts had dose reductions to 60 mg QD due to AEs, and 5 pts discontinued from the study due to an SAE. Forty-one pts were evaluable for efficacy, 1 pt discontinued from study due to SAE occurred at C1D12, 1 pt discontinued from the study due to withdrawing consent at C1D12, there were no post baseline imaging assessment for these patients. The overall response rate (ORR) was 61.0%, including 34.1% Complete Response (CR), 26.8% Partial Response (PR) and 26.8% Stable Disease, contributing to a 90.0% Disease Control Rate (DCR). CR and/or PR were observed in all PTCL histologies enrolled in this study. Nearly all responses occurred by the first assessment at day 58. AS of a data cut-off of July 22，2021, the median PFS was 10.3 months (95%CI: 4.4-NR) , and the duration of response was not reached (95%CI: 8.5-NR). As of a data cut-off of July 22, 2021, 17 pts still remain on the study treatment, 7 pts had received at least 10 months of linperlisib treatment. Discontinuations were most frequently due to disease progression (18, 41.9%), intolerable SAE (5, 11.6%), or withdrawal consent from the study (3, 7.0%). Conclusions The PI3Kd-selective oral agent, linperlisib, demonstrated promising efficacy and durable responses with a 61.0% ORR and 10.3 months median PFS in patients with r/r PTCL. Additional clinical studies of linperlisib in r/r PTCL, including a Phase 2 registration study, are currently ongoing. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nanatinostat (Nstat) and Valganciclovir (VGCV) in Relapsed/Refractory (R/R) Epstein-Barr Virus-Positive (EBV +) Lymphomas: Final Results from the Phase 1b/2 VT3996-201 Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 623-623
Author(s):  
Bradley M. Haverkos ◽  
Onder Alpdogan ◽  
Robert Baiocchi ◽  
Jonathan E Brammer ◽  
Tatyana A. Feldman ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Advisory Committees ◽  
Phase 1B

Abstract Introduction: EBV can be associated with several types of lymphomas, with reported frequencies of up to 8-10% in diffuse large B cell lymphoma (DLBCL), 30-100% in peripheral T cell lymphoma (PTCL) subtypes, 80% in post-transplant lymphoproliferative disease (PTLD), and 15-30% in classical Hodgkin lymphoma (HL), with adverse impact on outcomes. Nanatinostat (Nstat) is a Class-I selective oral HDAC inhibitor that induces the expression of the lytic BGLF4 EBV protein kinase in EBV + tumor cells, activating ganciclovir (GCV) via phosphorylation. This results in GCV-induced inhibition of viral and cellular DNA synthesis and apoptosis. Herein we report the final results from this exploratory study for patients with R/R EBV + lymphomas (NCT03397706). Methods: Patients aged ≥18 with histologically confirmed EBV + lymphomas (defined as any degree of EBER-ISH positivity), R/R to ≥1 prior systemic therapies with an absolute neutrophil count ≥1.0×10 9/L, platelet count ≥50×10 9/L, and no curative treatment options per investigator were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 doses (RP2D) of Nstat + VGCV for phase 2 expansion. Phase 2 patients received the RP2D (Nstat 20 mg daily, 4 days per week + VGCV 900 mg orally daily) in 28-day cycles until disease progression or withdrawal. Primary endpoints were safety/RP2D (phase 1b) and overall response rate (ORR) (phase 2); secondary endpoints were pharmacokinetics, duration of response (DoR), time to response, progression free survival and overall survival. Responses were assessed using Lugano 2014 response criteria beginning at week 8. Results: As of 18 June 2021, 55 patients were enrolled (phase 1b: 25; phase 2: 30). Lymphoma subtypes were DLBCL (n=7), extranodal NK/T-cell (ENKTL) (n=9), PTCL, not otherwise specified (PTCL-NOS) (n=5), angioimmunoblastic T cell lymphoma (n=6), cutaneous T cell (n=1), HL (n=11), other B cell (n=3), and immunodeficiency-associated lymphoproliferative disorders (IA-LPD) (n=13), including PTLD (n=4), HIV-associated (n=5), and other [n=4: systemic lupus erythematosus (SLE) (n=2), common variable/primary immunodeficiency (n=2)]. Median age was 60 years (range 19-84), M/F 35/20, median number of prior therapies was 2 (range 1-11), 76% had ≥2 prior therapies, 78% were refractory to their most recent prior therapy, and 84% had exhausted standard therapies. EBER positivity ranged from <1 to 90% in 42 tumor biopsies with central lab review. The most common treatment-emergent adverse events (TEAEs) of all grades were nausea (38%), neutropenia (34%), thrombocytopenia (34%), and constipation (31%). Grade 3/4 TEAEs in >10% of patients included neutropenia (27%), thrombocytopenia (20%), anemia (20%), and lymphopenia (14%). Dose reductions and interruptions due to treatment-related AEs were reported in 14 (25%) and 16 (29%) patients, respectively. Only 1 patient had to discontinue therapy. There were no cases of CMV reactivation. For 43 evaluable patients (EBER-ISH + with ≥ 1 post-treatment response assessment) across all histologies, the investigator-assessed ORR and complete response (CR) rates were 40% (17/43) and 19% (8/43) respectively. Patients with T/NK-NHL (n=15; all refractory to their last therapy) had an ORR of 60% (n=9) with 27% (n=4) CRs. Two patients (ENKTL and PTCL-NOS) in PR and CR respectively were withdrawn at 6.7 and 6.6 months (m) respectively for autologous stem cell transplantation. For DLBCL (n=6), ORR/CR was 67%/33% (both CRs were in patients refractory to first-line R-CHOP). For IA-LPD (n=13), ORR/CR was 30%/20% (PTLD: 1 CR, other: 1 CR, 1 PR). For HL (n=10), there was 1 PR (4 SD). The median DoR for all responders was 10.4 m, with a median follow-up from response of 5.7 m (range 1.9-34.1 m). For the 17 responders, 8 lasted ≥ 6 months. Conclusions: The combination of Nstat and VGCV was well-tolerated with a manageable toxicity profile and shows promising efficacy in patients with R/R EBV + lymphomas, particularly in refractory T/NK-NHL, a heterogeneous group of aggressive lymphomas with dismal outcomes, with multiple durable responses. Further evaluation of this novel combination therapy for the treatment of recurrent EBV + lymphomas is ongoing in the phase 2 VT3996-202 trial. Disclosures Haverkos: Viracta Therapeutics, Inc.: Honoraria, Research Funding. Baiocchi: Prelude Therapeutics: Consultancy; viracta: Consultancy, Current holder of stock options in a privately-held company; Codiak Biosciences: Research Funding; Atara Biotherapeutics: Consultancy. Brammer: Seattle Genetics: Speakers Bureau; Celgene: Research Funding; Kymera Therapeutics: Consultancy. Feldman: Alexion, AstraZeneca Rare Disease: Honoraria, Other: Study investigator. Brem: Karyopharm: Membership on an entity's Board of Directors or advisory committees; SeaGen: Speakers Bureau; BeiGene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; KiTE Pharma: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys/Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Scheinberg: Roche: Consultancy; Abbvie: Consultancy; BioCryst Pharmaceuticals: Consultancy; Alexion pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Joffe: AstraZeneca: Consultancy; Epizyme: Consultancy. Katkov: Viracta Therapeutics, Inc.: Current Employment. McRae: Viracta Therapeutics, Inc.: Current Employment. Royston: Viracta Therapeutics, Inc.: Current Employment. Rojkjaer: Viracta Therapeutics, Inc.: Current Employment. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy.

scholarly journals Combination of Chidamide with the CHOEP Regimen in Previously Untreated Patients with Peripheral T-Cell Lymphoma (PTCL): A Prospective, Multicenter, Single-Arm, Phase 1b/2 Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4036-4036
Author(s):  
Wei Zhang ◽  
Liping Su ◽  
Lihong Liu ◽  
Yuhuan Gao ◽  
Quanshun Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Histone Deacetylase ◽  
Primary Endpoint ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Peripheral T Cell Lymphoma ◽  
Phase 2 Study ◽  
Phase 1B

Background: Chidamide is a novel benzamide class of histone deacetylase (HDAC) inhibitor. In a pivotal phase 2 trial with refractory or relapsed peripheral T-cell lymphoma (PTCL), chidamide produced ORR 28% with CR 14% leading to its approval by the China Food and Drug Administration in 2014 for refractory or relapsed PTCL. We sought to assess the safety, tolerability and efficacy of the novel histone deacetylase inhibitor chidamide in combination with CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) (Chi-CHOEP) for previously untreated PTCL. Patients and methods: This was a prospective, multicenter, single-arm Phase 1b - 2 clinical trial conducted exclusively in China. In the phase 1b study, three dose levels of chidamide were explored. In the phase 2 portion, patients were treated at the RP2D. The primary endpoint of the Phase 1b was determination of the maximum tolerated dose (MTD), dose limiting toxicities (DLT) and RP2D. The primary endpoint of the phase 2 study was determination of the overall response rate (ORR). Results: A total of 82 patients were enrolled between March 2016 and Dec 2017 at 17 sites across China. The cutoff date for the analysis was July 2018. In phase 1b dose-escalation study, 15 patients were treated and the second dose cohort (20 mg biw) was declared the MTD and thus the RP2D. Subsequently, 67 patients were enrolled and treated at the RP2D in the phase 2 part of the study. Overall, among 82 enrolled patients in the entire phase 1b/2 study, the median number of cycles per person was five (range 1-8) and the relative dose intensity was 75.4%. The most common toxicities in the Phase 1b/2 study included leucopenia, anemia, and neutropenia. No reactivation of Epstein-Barr virus or Hepatitis B virus was observed. For entire phase 1b/2 study of 82 patients, the ORR was 68.3% with a CR rate of 43.9%. In the phase 2 part of the study, the ORR was 73.2% with 47.8% CR. with a median follow-up of 12.7 months (range 0.3-30.8 months), the median PFS for entire phase 1b/2 study was 17.4 months and the 1-year PFS was 52.9%. The median OS had not yet been reached, and the 1-year OS was 74.5%. In the phase 2 study, the median PFS was 17.4 months and the 1-year PFS was 53.6%. The median OS had not yet been reached, and the 1-year OS was 76.3%. Conclusion: Chi-CHOEP is an effective and feasible novel regimen for untreated PTCL. These data warrant further investigation in a randomized phase 3 study. This trial was registered at www.clinicaltrials.gov as #NCT02987244. Disclosures No relevant conflicts of interest to declare.

Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study.

1994 ◽  
Vol 12 (6) ◽  
pp. 1185-1192 ◽  
Author(s):  
A L Cheng ◽  
I J Su ◽  
C C Chen ◽  
H F Tien ◽  
J D Lay ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Lymphoma Cell ◽  
Peripheral T Cell Lymphoma ◽  
Retinoic Acids

PURPOSE We have systemically analyzed, both in vitro and in vivo, the effect of 13-cis-retinoic acids (RA) on non-Hodgkin's lymphoma (NHL). METHODS The in vitro growth-inhibitory effect of 13-cis-RA was examined in 11 (T cell, five; B cell, six) lymphoma cell lines by a tetrazolium colorimetric assay. A pilot clinical trial with oral 13-cis-RA 1 mg/kg/d was conducted in a selected group of 18 lymphoma patients, of whom 16 had failed to respond to at least one regimen of intensive chemotherapy. The in vitro and in vivo effects of 13-cis-RA were correlated with immunophenotypes, RA-induced changes of morphology, and patterns of DNA fragmentation of the lymphoma cells. RESULTS Four of five T-lymphoma cell lines and none of six B-lymphoma cell lines were sensitive (concentration of 50% growth inhibition [IC50] < 1.5 microns) to 13-cis-RA (P = .015). In the clinical trial, five (two Ki-1, one angioinvasive type, one diffuse mixed cell, and one diffuse large cell) complete remissions and one (Ki1) partial remission were observed in 12 patients with peripheral T-cell lymphoma (PTCL), while none of six patients with B-cell lymphoma responded to 13-cis-RA. 13-cis-RA-induced cellular differentiation and apoptosis, as evidenced by the more mature morphology, characteristic nuclear condensation, and DNA ladder pattern signifying internucleosomal fragmentation, were demonstrated in the sensitive cell lines, as well as in the remitting lymphoma tissues. CONCLUSION The 13-cis-RA appears to be active on lymphomas of T-lineage and their therapeutic indication may be extended to include some subtypes of PTCL. The mechanisms of action are related to differentiation and apoptosis of lymphoma cells. There appears to be no cross-resistance between 13-cis-RA and conventional chemotherapy.

Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma

2011 ◽  
Vol 61 (11) ◽  
pp. 662-666 ◽  
Author(s):  
Sho Yamazaki ◽  
Yosei Fujioka ◽  
Fumihiko Nakamura ◽  
Satoshi Ota ◽  
Aya Shinozaki ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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

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

Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

1989 ◽  
Vol 7 (6) ◽  
pp. 725-731 ◽  
Author(s):  
A L Cheng ◽  
Y C Chen ◽  
C H Wang ◽  
I J Su ◽  
H C Hsieh ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Induction Chemotherapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Grade ◽  
Peripheral T Cell Lymphoma ◽  
Laboratory Features ◽  
Hodgkin's Lymphomas

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.

Epstein–Barr virus-associated B-cell lymphoma secondary to FCD-C therapy in patients with peripheral T-cell lymphoma

2008 ◽  
Vol 88 (4) ◽  
pp. 434-440 ◽  
Author(s):  
Katja C. Weisel ◽  
Eckhart Weidmann ◽  
Ioannis Anagnostopoulos ◽  
Lothar Kanz ◽  
Antonio Pezzutto ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

Phase I Dose-Escalation Trial of BI 2536, a Polo-Like Kinase 1 Inhibitor, in Relapsed and Refractory Non-Hodgkin’s Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 233-233 ◽  
Author(s):  
Julie M. Vose ◽  
Anas Young ◽  
Jonathan W. Friedberg ◽  
Edmund K. Waller ◽  
Bruce D. Cheson ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Antitumor Activity ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
B Cell ◽  
Cell Transplantation ◽  
Safety Profile ◽  
Cell Lymphoma ◽  
Bi 2536

Abstract Background: BI 2536 is a highly potent, selective inhibitor of Polo-like kinase 1 (Plk1), a key regulator of mitotic progression. BI 2536 has demonstrated favorable tolerability and antitumor activity in Phase I trials in patients with solid tumors. Antitumor activity of BI 2536 was also shown in preclinical non-Hodgkin’s lymphoma (NHL) models. We determined the maximum tolerated dose (MTD), overall safety, pharmacokinetics (PK) and efficacy of BI 2536 given as an intravenous infusion once every 3 weeks in patients with relapsed or refractory aggressive NHL of T- or B-cell origin. Methods: Sequential cohorts of 3–6 patients with relapsed or refractory aggressive NHL received 1-hour infusions of BI 2536 following a toxicity-guided Phase 1 doseescalation design. Patients relapsed after peripheral stem cell transplantation and transplantation-naive patients were entered into different strata and the respective MTD determined independently. A single administration was given every 21 days. Patients with clinical benefit were eligible for further treatment courses after recovery from toxicity after a 3-week observation period. A total of 41 patients were entered into the trial: 24 patients in the transplant-naive (non-tr) stratum; and 17 patients in the transplant-failure (tr) stratum. Patients were treated at dose levels from 50 to 200 mg. Results: The safety profile was similar in both strata with the MTD determined independently at 175 mg for both non-tr and tr patients. Neutropenia (tot: 33%; CTCAE Grade (gr)3/4: 21%), anemia (tot: 29%; gr3: 4%), thrombocytopenia (tot: 29%; gr3/4: 17%), fatigue (tot: 25%; gr3: 4%) and nausea (tot=gr1/2: 25%) were the most frequent adverse events in non-tr; and thrombocytopenia (tot: 59%; gr3/4: 41%), anemia (tot=gr1/2: 41%), fatigue (tot=gr1/2: 41%) and neutropenia (tot: 41%; gr3/4: 21%) were most frequent in tr patients. Dose-limiting toxicities (DLTs) consisted of reversible thrombocytopenia (six patients) and neutropenia (three patients). No relevant non-specific toxicity was observed. Pharmacokinetic analysis showed dose proportionality of Cmax and AUC0–∞ with a high clearance (~1,400 mL/min) and a high volume of distribution (&gt;1,000 L). Patients were treated for up to 6 courses without evidence of cumulative toxicity. Three complete responses (CRs) and one partial response were observed. Stable disease as best response was noted in three (18%) of tr patients and nine (38%) of non-tr patients. All responders had relapsed after prior peripheral stem cell transplants and were treated at doses of 150–200 mg. Three of the four responders had a peripheral T-cell lymphoma (PTCL) NHL; one CR was observed in a patient with diffuse large B-cell lymphoma. The overall response rate (ORR) in the tr stratum was 23.5%; in the aggregate of both tr and non-tr, the ORR amounted to 9.7%. With three out of five patients responding, an ORR of 60% was observed in the T-cell subset. However, the responses were of short duration. Conclusion: BI 2536 has a favorable safety and PK profile in patients with NHL. Safety profile and PK properties are comparable to data obtained in solid tumor patient populations. Encouraging, albeit transient, anti-lymphoma efficacy was observed in patients suffering from PTCL after autologous stem-cell transplantation.

Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE): First Detailed Report of Primary Treatment

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1614-1614 ◽  
Author(s):  
Francine M. Foss ◽  
Kenneth R. Carson ◽  
Lauren Pinter-Brown ◽  
Steven M. Horwitz ◽  
Steven T. Rosen ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Initial Treatment ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Treatment ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Advisory Committees

Abstract 1614 Background: Registries can be invaluable for describing patterns of care for a population of patients. COMPLETE is a registry of peripheral T-cell lymphoma (PTCL) patients designed to identify the lymphoma-directed treatments and supportive care measures that PTCL patients receive. We report here the first detailed findings of initial therapy. Methods: This is a prospective, longitudinal, observational registry that is led by a global steering committee. Patients with newly diagnosed PTCL and providing written informed consent are eligible. Patients are entered into the registry from time of initial diagnosis and followed for up to 5 years. Only locked records are reported. Results: As of July 2012, 330 patients have been enrolled from the United States. The first patient was enrolled in February 2010. Locked baseline and treatment records are available for 124 and 81 patients, respectively. Of the 124 patients with locked baseline records, 67 patients (54%) were male, the mean age was 59 (range: 19–89), and race/ethnicity was recorded as: White (87 patients; 70%), Black (19; 15%), Asian (5; 4%) and other/unknown (13; 11%). Histology was reported as follows: PTCL-not otherwise specified (27%), anaplastic large cell lymphoma-primary systemic type (18%), angioimmunoblastic T-cell lymphoma (17%), transformed mycosis fungoides (7%), T/NK-cell lymphoma-nasal and nasal type (6%), adult T-cell leukemia/lymphoma, HTLV 1+ (6%) and other (19%). 25 patients (20%) had received another diagnosis, including B-cell lymphoma, Hodgkin's disease and other T-cell lymphomas, prior to their current diagnosis of PTCL. 49 patients (40%) had B symptoms, 102 patients (82%) had an Ann Arbor stage of III/IV, 116 patients (94%) had ECOG performance status of 0–1, and international prognostic index (IPI) score was distributed as follows: IPI 0 (7% of patients), 1 (15%), 2 (43%), 3 (26%), and 4 (9%). Of the 81 patients with locked treatment records, details on initial treatment can be found in table below. Conclusions: This first detailed analysis of primary treatment of PTCL indicates that this disease is still largely being treated with regimens derived primarily from studies of B-cell lymphomas and that a single standard of care does not exist. The fact that a meaningful proportion of patients were initially diagnosed with something other than their current diagnosis of PTCL points out the challenges of diagnosing the disease. While the intent of initial treatment for most patients is to affect a cure, more than 20% of patients were noted as deceased at the end of initial treatment, underscoring the need for more effective, disease-specific therapy. Disclosures: Foss: Merck: Study Grant, Study Grant Other; Celgene: Study Grant, Study Grant Other; Eisai: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Allos: Consultancy. Carson:Allos: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Pinter-Brown:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos: Consultancy, Research Funding. Rosen:Allos: Consultancy, Honoraria. Pro:Celgene: Honoraria, Research Funding; Spectrum: Honoraria; Allos: Honoraria; Seattle Genetics: Research Funding. Gisselbrecht:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hsi:Allos: Research Funding; Eli Lilly: Research Funding; Abbott: Research Funding; Cellerant Therapeutics: Research Funding; BD Biosciences: Research Funding; Millenium: Research Funding.

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