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Journal of Clinical Oncology 04/2013; · 18.37 Impact Factor
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ABSTRACT: Abstract Background: We previously reported that (18)F fluoro-deoxy-glucose positron emission tomography scan (FDG-PET) is almost universally positive in patients with T cell lymphoma. In the current analysis we examined the impact of FDG-PET in the initial staging of peripheral T cell lymphomas (PTCL), and prognostic value of interim FDG-PET. Methods: This retrospective analysis identified patients with mature T or NK lymphomas who had PET scans as part of initial staging or staging at relapse [(N=95) (staging cohort)] in the peripheral T cell lymphoma (PTCL) database at Memorial Sloan-Kettering Cancer Center. A subset of these patients had repeat PET for interim restaging during initial therapy with curative intent [(N=50) (interim restaging cohort)]. Results: The frequency of specific T cell histologies included in this analysis were: PTCL not otherwise specified (NOS) (N=35); angioimmunoblastic T cell lymphoma (AITL) (N=17); anaplastic large cell lymphoma (ALCL), ALK-1+ (N=11) and ALK-1- (N=12); adult T cell lymphoma/leukemia (ATLL) (N=7); NK/T cell lymphoma (NKTCL) (N=10); enteropathy-associated T cell lymphoma (EATL) (N=3). In the staging cohort, 77 patients were newly diagnosed, 18 had relapsed disease. Pretreatment FDG-PET was positive in 96% of patients. PET identified additional disease sites in 47/95 patients (50%) when added to conventional staging. Most frequently identified additional sites were: other nodal (N=24); bone (N=10); skin (N=8); nasopharynx (N=4); spleen (N=3); and lung (N=2). However, FDG-PET modified CT-based staging in only 5/95 patients (5.2%): 2 patients were upstaged and 3 patients were downstaged. FDG-PET-based staging did not alter planned treatment for any patient. Interim restaging with PET was performed after a median of 4 cycles of chemotherapy. In this cohort, treatment regimens included CHOP (N=19); CHOP/ICE (N=24); other (N=7). Subsequently, 29 patients were consolidated with either autologous (N=22) or allogeneic (N=7) stem cell transplant. After a median follow up of 3.4 years for surviving patients, those with negative interim PET had superior progression free survival (PFS) compared to patients with positive interim PET (p 0.03). There were no differences in overall survival (OS). Conclusions: In PTCL, FDG-PET commonly identifies additional sites of disease but infrequently impact CT-based staging and does not influence therapy. Interim FDG-PET may predict for PFS. FDG-PET should be integrated into prospective trials to confirm these findings.
Leukemia & lymphoma 02/2013; · 2.40 Impact Factor
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ABSTRACT: Extracorporeal photopheresis (ECP) is effective for treating cutaneous T-cell lymphoma. In 1987, a pivotal trial showed 81% overall response rate (ORR) using outdated criteria. No long-term follow-up was available for assessing survival. This study applies modern criteria to the 1987 trial to assess the impact of ECP on skin responses and also updates overall survival of the cohort.
Generalized erythroderma (GE, stage T4, n = 31) or extensive patch-plaque (EPP, stage T2, n = 8) patients received ECP (mean 3.9 years' duration). Patients achieving ≥ 50% partial skin response, ≥ 90% near-complete skin response, treatments required, and duration of response (DOR) were determined. Overall survival (OS) from diagnosis and first ECP treatment was determined for all patients and the GE cohort.
Patients showed 74% skin ORR using modern criteria; 33% of patients achieved ≥ 50% partial skin response (after median 7.1 months, mean 23 ECP treatments); 41% achieved ≥ 90% improvement (after median 19.6 months, mean 40 ECP treatments). Mean DOR was 14 months for ≥ 50% improvement and 8.9 months for ≥ 90% improvement. Response rates were comparable for GE and EPP cohorts. Median OS was 9.2 years from diagnosis and 6.6 years from ECP initiation (71.6 months follow-up).
Analysis of long-term follow-up confirmed durable responses and prolonged survival of patients treated with ECP.
Photodermatology Photoimmunology and Photomedicine 10/2012; 28(5):250-7. · 1.30 Impact Factor
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Bertrand Coiffier,
Barbara Pro,
H Miles Prince,
Francine Foss,
Lubomir Sokol,
Matthew Greenwood,
Dolores Caballero,
Peter Borchmann,
Franck Morschhauser,
Martin Wilhelm,
Lauren Pinter-Brown,
Swaminathan Padmanabhan,
Andrei Shustov,
Jean Nichols,
Susan Carroll,
John Balser,
Barbara Balser, Steven Horwitz
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ABSTRACT: 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 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/m(2) 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.
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%).
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.
Journal of Clinical Oncology 02/2012; 30(6):631-6. · 18.37 Impact Factor
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Neha Mehta,
Alan S Wayne,
Youn H Kim,
Gregory A Hale,
Carlos S Alvarado,
Patricia Myskowski,
Elaine S Jaffe,
Klaus J Busam,
Melissa Pulitzer,
Jeffrey Zwerner, Steven Horwitz
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ABSTRACT: Subcutaneous panniculitis-like T-cell lymphoma (SPTL-AB) and cutaneous gamma/delta T-cell lymphoma (CGD-TCL) are rare T-cell lymphomas with varying clinical courses. There is no standard treatment, although chemotherapy and hematopoietic stem cell transplantation are commonly used. We describe results using bexarotene for children and adults with these disorders.
We identified 15 patients (12 adults, 3 children) who were treated with bexarotene between 2000 and 2010 from the Memorial Sloan-Kettering Cancer Center lymphoma database, the Stanford Cancer Center Registry, and the National Cancer Institute (NCI) pediatric lymphoma database. There were 8 females and 7 males, with a median age of 45 years (range, 3 years to 85 years). All patients had stage IV disease. Two of 15 and 4 of 15 patients had documented CGD-TCL and SPTL-AB, respectively; others were presumed to have SPTL-AB. Bexarotene was administered at flat doses corresponding to 91 to 339 mg/m(2)/d. Two of 15 patients received concurrent denileukin diftitox. Two children received bexarotene as maintenance therapy and were not evaluable for response.
Among those treated with bexarotene alone, the overall response rate (ORR) was 82% (6/11 complete response [CR], 3/11 partial response [PR]). One of the 2 patients treated with concomitant denileukin diftitox responded for an ORR of 10/13 (77%), including 54% CR and 23% PR. Median progression-free survival was 38.4 months; median duration of response was 26.3 months. Six patients developed hypothyroidism and 9 developed hyperlipidemia; one patient developed dose-limiting hypertriglyceridemia. One pediatric patient developed insulin-dependent diabetes mellitus.
In this retrospective series, bexarotene showed a high response rate in SPTL-AB and CGD-TCL. It was generally well-tolerated with durable responses; therefore, bexarotene represents a promising therapy for children and adults with these disorders.
Clinical lymphoma, myeloma & leukemia 02/2012; 12(1):20-5.
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Craig H Moskowitz,
Matt J Matasar,
Andrew D Zelenetz,
Stephen D Nimer,
John Gerecitano,
Paul Hamlin, Steven Horwitz,
Alison J Moskowitz,
Ariela Noy,
Lia Palomba,
Miguel-Angel Perales,
Carol Portlock,
David Straus,
Jocelyn C Maragulia,
Heiko Schoder,
Joachim Yahalom
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ABSTRACT: We previously reported that remission duration < 1 year, extranodal disease, and B symptoms before salvage chemotherapy (SLT) can stratify relapsed or refractory Hodgkin lymphoma (HL) patients into favorable and unfavorable cohorts. In addition, pre-autologous stem cell transplant (ASCT) (18)FDG-PET response to SLT predicts outcome. This phase 2 study uses both pre-SLT prognostic factors and post-SLT FDG-PET response in a risk-adapted approach to improve PFS after high-dose radio-chemotherapy (HDT) and ASCT. The first SLT uses 2 cycles of ICE in a standard or augmented dose (ICE/aICE), followed by restaging FDG-PET scan. Patients with a negative scan received a transplant. If the FDG-PET scan remained positive, patients received 4 biweekly doses of gemcitabine, vinorelbine, and liposomal doxorubicin. Patients without evidence of disease progression proceeded to HDT/ASCT; those with progressive disease were study failures. At a median follow-up of 51 months, EFS analyzed by intent to treat as well as for transplanted patients is 70% and 79%, respectively. Patients transplanted with negative FDG-PET, pre-HDT/ASCT after 1 or 2 SLT programs, had an EFS of > 80%, versus 28.6% for patients with a positive scan (P < .001). This prospective study provides evidence that the goal of SLT in patients with Hodgkin lymphoma should be a negative FDG-PET scan before HDT/ASCT.
Blood 12/2011; 119(7):1665-70. · 9.90 Impact Factor
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Jenna D Goldberg,
Joanne F Chou, Steven Horwitz,
Julie Teruya-Feldstein,
Juliet N Barker,
Farid Boulad,
Hugo Castro-Malaspina,
Sergio Giralt,
Ann A Jakubowski,
Guenther Koehne,
Marcel R M van den Brink,
James W Young,
Zhigang Zhang,
Esperanza B Papadopoulos,
Miguel-Angel Perales
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ABSTRACT: Peripheral T-cell non-Hodgkin lymphomas (T-NHL) are rare diseases, with a worse prognosis compared to their B-cell counterparts. Allogeneic hematopoietic stem cell transplant may have a role in the treatment of relapsed/refractory disease or high-risk histologies in the upfront setting. However, there is limited information on the efficacy of allogeneic transplant for these diseases, as well as what factors may predict outcomes. We therefore performed a retrospective study of 34 patients who received an allogeneic transplant for the treatment of T-NHL at a single center between 1 January 1992 and 31 December 2009. The median follow-up for survivors was 45 months (range 9-160 months). The 2-year overall survival (OS) was 0.61 (95% confidence interval [CI]: 0.43-0.75) with a plateau at 28 months. Ki-67 expression ≤ 25% was predictive of improved OS (p < 0.01), and transplant in complete remission was predictive of a decreased cumulative incidence of events (p = 0.04). Three patients received a donor leukocyte infusion, and two patients demonstrated a response, supporting a graft-versus-lymphoma effect. These data demonstrate that allogeneic transplant is a viable option for the treatment of T-NHL and merits prospective evaluation.
Leukemia & lymphoma 12/2011; 53(6):1124-9. · 2.40 Impact Factor
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Elise A Olsen,
Sean Whittaker,
Youn H Kim,
Madeleine Duvic,
H Miles Prince,
Stuart R Lessin,
Gary S Wood,
Rein Willemze,
Marie-France Demierre,
Nicola Pimpinelli, [......],
Michael Girardi,
Günter Burg,
Annamari Ranki,
Maartan Vermeer, Steven Horwitz,
Peter Heald,
Steve Rosen,
Lorenzo Cerroni,
Brigette Dreno,
Eric C Vonderheid
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ABSTRACT: Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.
Journal of Clinical Oncology 06/2011; 29(18):2598-607. · 18.37 Impact Factor
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Owen A O'Connor,
Barbara Pro,
Lauren Pinter-Brown,
Nancy Bartlett,
Leslie Popplewell,
Bertrand Coiffier,
Mary Jo Lechowicz,
Kerry J Savage,
Andrei R Shustov,
Christian Gisselbrecht,
Eric Jacobsen,
Pier Luigi Zinzani,
Richard Furman,
Andre Goy,
Corinne Haioun,
Michael Crump,
Jasmine M Zain,
Eric Hsi,
Adam Boyd, Steven Horwitz
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ABSTRACT: 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 with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m(2)/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).
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%).
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.
Journal of Clinical Oncology 01/2011; 29(9):1182-9. · 18.37 Impact Factor
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ABSTRACT: Peripheral T-cell lymphomas (PTCL) are rare and aggressive subtypes of non-Hodgkin's lymphoma. Compared to B cell lymphomas, the immunologic phenotype of PTCL portends a poorer prognosis, with the exception of anaplastic large cell lymphoma bearing the anaplastic lymphoma kinase protein. Patients with PTCL tend to present clinically in advanced disease states, show lower response rates to chemotherapy, and suffer from more frequent relapses and shorter remissions. The rarity of these lymphomas has made it difficult to carry out prospective, randomized trials delineating optimal treatments. Conventional and intensified chemotherapy have led to reasonable responses, but in many studies, frequent relapses. Consequently, high-dose chemotherapy and autologous stem cell transplantation (ASCT) have been actively studied in both the relapsed and upfront setting. In addition, the impact of disease status at transplantation is being investigated, though the optimal disease state at transplant is still a matter of debate, as is the timing of transplant. This article seeks to review the literature on the role of ASCT in PTCL, as well as to clarify what may be the optimal disease state in which to offer patients with PTCL autologous transplantation, if at all.
Current Oncology Reports 11/2010; 12(6):374-82. · 2.55 Impact Factor
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ABSTRACT: The purpose of this article is to describe the utility of FDG PET/CT in documenting sites of disease in patients with T-cell lymphomas, to quantify the degree of FDG avidity in the various subtypes of this heterogeneous group of disorders, and to highlight the pattern of imaging findings associated with specific disease subtypes.
A retrospective review of patients with T-cell lymphomas who underwent PET/CT examination for initial disease staging or at disease relapse over a 5-year period was undertaken by correlation between a patient database and a PACS radiology information system. Disease subtypes were grouped according to World Health Organization categorization of mature natural killer cell-T-cell neoplasms. Sites of disease involvement were documented according to cutaneous or extranodal, nodal, and visceral locations. The maximum standardized uptake value (SUV) was recorded for each patient.
One hundred thirty-five patients with T-cell lymphoma were included, and sites of disease were documented by use of FDG PET/CT in 122 (90%) patients. Of those 122 patients, 55 (45%) had cutaneous involvement, 95 (78%) had FDG-avid lymphadenopathy, and 54 (44%) had FDG-avid extranodal disease other than cutaneous involvement. A significant difference in maximum SUV was observed in cases of mycosis fungoides and mycosis fungoides with large cell transformation (SUV, 11.3 vs 3.8; p < 0.05).
We found high rates of FDG positivity in T-cell lymphoma. Given the propensity for disease involvement outside the normal scan range of diagnostic CT, we recommend that patients with T-cell lymphoma be scanned from vertex to feet by use of PET/CT.
American Journal of Roentgenology 08/2010; 195(2):333-40. · 2.78 Impact Factor
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Craig H Moskowitz,
Heiko Schöder,
Julie Teruya-Feldstein,
Camelia Sima,
Alexia Iasonos,
Carol S Portlock,
David Straus,
Ariela Noy,
Maria L Palomba,
Owen A O'Connor, Steven Horwitz,
Sarah A Weaver,
Jessica L Meikle,
Daniel A Filippa,
James F Caravelli,
Paul A Hamlin,
Andrew D Zelenetz
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ABSTRACT: PURPOSE In studies of diffuse large B-cell lymphoma, positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. PATIENTS AND METHODS From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. RESULTS At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.
Journal of Clinical Oncology 03/2010; 28(11):1896-903. · 18.37 Impact Factor
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Owen A O'Connor, Steven Horwitz,
Paul Hamlin,
Carol Portlock,
Craig H Moskowitz,
Debra Sarasohn,
Ellen Neylon,
Jill Mastrella,
Rachel Hamelers,
Barbara Macgregor-Cortelli,
Molly Patterson,
Venkatraman E Seshan,
Frank Sirotnak,
Martin Fleisher,
Diane R Mould,
Mike Saunders,
Andrew D Zelenetz
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ABSTRACT: To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma.
Pralatrexate, initially given at a dose of 135 mg/m(2) on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m(2) weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/microL, and a platelet count greater than 50,000/microL for the first dose of any cycle.
The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m(2) weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months.
Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma.
Journal of Clinical Oncology 09/2009; 27(26):4357-64. · 18.37 Impact Factor
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Leukemia & lymphoma 05/2009; 50(6):1039-42. · 2.40 Impact Factor
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Steven M Horwitz
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ABSTRACT: Cutaneous T-cell lymphomas (CTCLs) are a group of uncommon mature T-cell lymphomas presenting primarily or exclusively in the skin. The most common subtype, mycosis fungoides and its leukemic variant Sézary syndrome, frequently behave as a chronic lymphoma with good prognosis for early-stage disease and shortened survival only for patients in advanced stages. Historically, these patients have experienced excessive toxicity from chemotherapy without durable benefit, leading to current conservative treatment strategies. An increasing number of novel therapies are available or in development. These newer therapies often have unique mechanisms of action and different toxicities with less myelosuppression than traditional cytotoxic chemotherapy. Among these novel systemic therapies are so-called biologic therapies such as retinoids like bexarotene, the fusion toxin denileukin diftitox, lenalidomide, and toll-like receptor agonists. Other important novel or emerging agents include the histone deacetylase inhibitors; a novel antifolate, pralatrexate; the proteasome inhibitor bortezomib; and the purine nucleoside phosphorylase inhibitor forodesine. Even agents considered to be conventional chemotherapy, such as gemcitabine or pegylated liposomal doxorubicin, have demonstrated activity in CTCL at relatively lower doses with less myelosuppression. The mechanisms of action of the novel agents are reviewed as well as available clinical data. As the role of these new agents is better understood, particularly with regard to nonoverlapping toxicities, combination strategies might emerge. Evaluation through carefully designed clinical trials should lead to better, safer, and more effective treatment strategies in the future.
Clinical Lymphoma & Myeloma 01/2009; 8 Suppl 5:S187-92. · 1.13 Impact Factor
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Owen A O'Connor,
Paul A Hamlin,
Carol Portlock,
Craig H Moskowitz,
Ariela Noy,
David J Straus,
Barbara Macgregor-Cortelli,
Ellen Neylon,
Debra Sarasohn,
Otila Dumetrescu,
Diane R Mould,
Martin Fleischer,
Andrew D Zelenetz,
Frank Sirotnak, Steven Horwitz
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ABSTRACT: T-cell lymphomas (TCLs) are characterised by poor responses to therapy with brief durations of remissions. An early phase study of pralatrexate has demonstrated dramatic activity in patients with relapsed/refractory disease. Of the first 20 lymphoma patients treated, 16 had B-cell lymphoma and four had refractory aggressive TCL. All four patients with TCL achieved a complete remission. Patients with B-cell lymphoma achieved stable disease at best. For each TCL patient, the response was more durable than their best response with chemotherapy. This early experience is the first to document this unique activity of pralatrexate in TCL.
British Journal of Haematology 12/2007; 139(3):425-8. · 4.94 Impact Factor
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ABSTRACT: Bexarotene is one of the most active single agents for the treatment of recurring or refractory cutaneous T-cell lymphoma (CTCL). Interferon alfa has also been used for many years as an effective treatment for this disease. The results in recent case reports of the combination of bexarotene and interferon alfa have been promising. Based on more extensive results reported with the combination of other retinoids with interferon alfa, the present study attempted to determine the response rate, response duration, and safety of bexarotene (Targretin capsules, Ligand Pharmaceuticals, San Diego, Calif) alone and then with the addition of interferon alfa-2b (Intron-A, Schering-Plough, Kenilworth, NJ).
Patients with biopsy-proven CTCL, TNM stages IB, IIA, IIB-IV, were treated with oral bexarotene 300 mg/m2/day for at least 8 weeks. If a complete response was not seen after 8 weeks, interferon alfa-2b 3 million units (MU) subcutaneously was added, and increased to 5 MU if tolerated, 3 times a week.
A total of 22 patients were enrolled at 5 sites, and 18 patients were assessable for response. Overall response rate for combined bexarotene and interferon alfa was 39% (95% confidence interval [CI]: 17%-64%), including 1 patient with a clinical complete response, 6 patients with partial response, 3 patients with stable disease, and 8 patients with progressive disease. Three partial responses were first noted during the bexarotene-alone phase. Adverse events were generally manageable, and only 1 patient was withdrawn from study for hypertriglyceridemia.
The addition of interferon alfa-2b did not increase the response rate that would have been expected with bexarotene alone.
Cancer 06/2007; 109(9):1799-803. · 4.77 Impact Factor
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ABSTRACT: Angioimmunoblastic T cell lymphoma is a distinct entity for which there is no standard therapy. On the basis of the rationale that CsA may represent a novel drug for AITL, a disease with considerable immune dysregulation, and encouraging case reports, the authors have treated 12 patients with this agent. Ten had failed prior steroids and/or chemotherapy and two had no prior therapy. CsA was administered at a dose of 3 - 5 mg/kg PO bid for 6 - 8 weeks and gradually tapered by 50 mg every 1 - 3 weeks. Responding patients received a maintenance dose of 50 - 100 mg, with a gradual taper after a maximal response was achieved as tolerated. Doses were titrated for renal dysfunction or hypertension. CsA levels were not monitored. Eight of 12 patients responded (three complete and five partial remissions). Dose reductions were required in six patients; renal insufficiency (n = 3), fatigue (n = 2), and hypertension (n = 1). Two patients developed acute infections and one patient died shortly after active treatment. These results suggest that CsA deserves further testing as a novel therapy for AITL. By interrupting T-cell activation, CsA may alter the immune dysregulation that characterizes AILT. The efficacy of CsA is being explored in patients with recurrent AILT in a prospective trial (ECOG 2402).
Leukemia and Lymphoma 04/2007; 48(3):521-5. · 2.58 Impact Factor
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ABSTRACT: Autologous transplantation (ASCT) is the standard of care for chemosensitive relapsed or primary refractory aggressive lymphoma, but little is known about its efficacy in the subset of patients with peripheral T-cell lymphoma (PTCL). We undertook a retrospective review of patients with PTCL who underwent ASCT for relapsed or refractory disease after responding to second-line therapy, excluding patients with indolent histologies and those with anaplastic lymphoma kinase (ALK) expressing anaplastic large cell lymphoma. The results of 24 patients with PTCL were compared with those of 86 consecutive patients with chemosensitive relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL). With a median follow-up time of 6 years for surviving patients with PTCL and DLBCL, the 5-year progression-free survival (PFS) rates for PTCL and DLBCL patients were 24% and 34% respectively (P = 0.14); the corresponding overall survival (OS) rates were 33% and 39% respectively. There were no significant differences between the two groups with respect to time to disease progression or survival after progression. The second-line age-adjusted international prognostic index was the only variable prognostic for PFS and OS in a multivariate analysis. The outcome of ASCT for patients with chemosensitive relapsed or primary refractory PTCL is similar to that for patients with DLBCL.
British Journal of Haematology 08/2006; 134(2):202-7. · 4.94 Impact Factor
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Owen A O'Connor,
Mark L Heaney,
Lawrence Schwartz,
Stacie Richardson,
Robert Willim,
Barbara MacGregor-Cortelli,
Tracey Curly,
Craig Moskowitz,
Carol Portlock, Steven Horwitz,
Andrew D Zelenetz,
Stanley Frankel,
Victoria Richon,
Paul Marks,
William K Kelly
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ABSTRACT: To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies.
Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both trials, dose escalation was performed in parallel and independently in patients with solid tumors and hematologic malignancies. Eligible patients were required to have adequate hepatic and renal function, an absolute neutrophil count > or = 500/microL and a platelet count more than 25,000/mL. All patients provided informed consent for study inclusion.
A total of 39 patients with hematologic malignancy were enrolled (14 on IV SAHA and 25 on oral SAHA), of whom 35 were treated. The spectrum of diseases included patients with diffuse large B-cell lymphoma (n = 12), Hodgkin's disease (HD; n = 12), multiple myeloma (n = 2), T-cell lymphoma (n = 3), mantle cell lymphoma (n = 2), small lymphocytic lymphoma (n = 2), and myeloid leukemia (n = 2). Major adverse events with the oral formulation included fatigue, diarrhea, anorexia, and dehydration, whereas myelosuppression and thrombocytopenia were more prominent with the IV formulation. Typically, the hematologic toxicities resolved shortly after SAHA was stopped. There was no neutropenic fever or neutropenic sepsis. Reduction in measurable tumor was observed in five patients. One patient with transformed small lymphocytic lymphoma met criteria for complete response, whereas another met the criteria for partial response (PR). One patient with refractory HD had a PR, whereas three patients had stable disease for up to 9 months.
These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.
Journal of Clinical Oncology 01/2006; 24(1):166-73. · 18.37 Impact Factor
