Lymphoma

NEW ORLEANS-For 25 years, oncologists made no progress in treating diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL). Then, in 2000, the anti-CD20 antibody rituximab (Rituxan, MabThera in Europe) was shown to improve results in

The field of radioimmunotherapy for the treatment of non-Hodgkin'slymphoma (NHL) has advanced significantly over the past decade, andseveral radioimmunoconjugates are being tested in clinical trials. Twoof these antibodies target CD20: yttrium-90 (Y-90)-labeled ibritumomabtiuxetan (Zevalin) and tositumomab/iodine-131 (I-131)-labeledtositumomab (Bexxar). Other agents target either CD22 (Y-90epratuzumab) or human leukocyte antigen (HLA)-DR (I-131 Lym-1),respectively. In February 2002, Y-90-labeled ibritumomab tiuxetanbecame the first radioimmunoconjugate to be approved by the US Foodand Drug Administration (FDA) for the treatment of cancer.Tositumomab/I-131 tositumomab was approved in June 2003. Thus,two radioimmunoconjugates have been approved for the treatment ofNHL. Both agents, when administered as a single dose, have producedimpressive tumor response rates with an acceptable toxicity profile. Themain side effect is reversible myelosuppression. Radioimmunotherapyproduces overall response rates of approximately 80% in patients withlow-grade lymphomas, and 25% to 30% of patients achieve a completeremission. Lower response rates (approximately 40%) have been reportedin patients with large-cell lymphomas. This review discusses theclinical trials of radioimmunotherapeutic agents for NHL that demonstratedtheir safety and efficacy and outlines the current status of theseagents.

SAN DIEGO-In the IRIS study, newly diagnosed chronic myelogenous leukemia (CML) patients who crossed over from interferon (IFN)-alfa plus cytarabine (ara-C) to imatinib mesylate (Gleevec) and achieved a complete cytogenetic response (CCR = elimination of Ph+ cells), had reductions in bcr-abl similar to those on first-line imatinib, according to a presentation at the 45th Annual Meeting of the American Society of Hematology (ASH abstract 635). Their probability of achieving a CCR, is somewhat diminished, however, compared with those treated with first-line imatinib, said Jerald P. Radich, MD, Fred Hutchinson Cancer Research Center, Seattle.

Together, parts 1 and 2 of thearticle by Drs. Wilson andSmith on the “Management ofMycosis Fungoides” serve as an excellentreference for the diagnosis andmanagement of this subtype of cutaneousT-cell lymphoma. Part 1, whichdeals with the diagnosis, staging, andprognosis of mycosis fungoides, appearedin the September 2003 issue ofthis journal. Part 2, which deals withtreatment, appears in the current issue.The article is a concise overviewof the numerous treatment strategiesand specific treatments available forvarious stages and presentations ofmycosis fungoides.

Mycosis fungoides is a low-grade lymphoproliferative disorder ofskin-homing CD4+ lymphocytes that may produce patches, plaques,tumors, erythroderma, and, ultimately, systemic dissemination. Treatmentselection is generally guided by institutional experience, patientpreference, and toxicity profile, as data from phase III clinical trials arelimited. Effective topical treatments currently include mechlorethamine(Mustargen), carmustine (BCNU, BiCNU), corticosteroids, bexarotene(Targretin, a novel rexinoid), psoralen plus ultraviolet A, ultraviolet B,and total-skin electron-beam radiotherapy. Effective systemic treatmentsinclude interferon, retinoids, bexarotene, denileukin diftitox(Ontak), extracorporeal photopheresis, chemotherapy, and high-dosechemotherapy with allogeneic bone marrow transplant. Each of thesetreatments is discussed in detail, followed by specific recommendationsfor each stage of mycosis fungoides.

Mantle cell lymphoma (MCL) accounts for approximately 6% of non-Hodgkin’s lymphomas. Patients usually present with advanced disease, with a tendency for extranodal involvement. MCL is an aggressive lymphoma with moderate chemosensitivity, but it remains one of the most difficult therapeutic challenges. Complete response rates to chemotherapy range from 20% to 40%, with median survivals of 2½ to 3 years. Anthracycline-containing regimens do not prolong survival compared with nonanthracycline regimens. Single-agent rituximab (Rituxan) has produced response rates of about 30%, and when combined with an anthracycline-containing regimen, response rates increase to above 90%; however, an impact on survival has not yet been demonstrated. More intensive regimens such as hyperCVAD (hyperfractionated cyclophosphamide [Cytoxan, Neosar], vincristine, doxorubicin [Adriamycin], dexamethasone, methotrexate, cytarabine) with either stem cell transplant or rituximab have been associated with promising results.

Drs. Baidas, Cheson, Kauh, and Ozdemirli present a thorough and balanced review of mantle cell lymphoma (MCL) and the various current treatment options. MCL has been recognized as a distinct pathologic entity for over a decade. It represents 6% to 9% of all non- Hodgkin’s lymphoma cases, and the diagnosis is based on a combination of morphologic, immunophenotypic, and cytogenetic criteria as discussed in the article. The hallmark of MCL is t(11;14)(q13;q32), a translocation that juxtaposes the Bcl-1 gene on chromosome 11 and immunoglobulin (Ig)H promoter on chromosome 14, leading to overexpression of cyclin D1. Although it had been considered an indolent lymphoma for many years, MCL has a poor prognosis with short remissions and a median survival of 3 to 4 years.[1,2]

This special supplement to Oncology News International includes updated results of studies with anti-CD20 therapy and other targeted therapies in the treatment of lymphomas, chronic lymphocytic leukemia, and immune thrombocytopenic purpura. The results were presented at the American Society of Hematology 44th Annual Meeting in Philadelphia, December 6 to 10, 2002.

This special supplement to Oncology News International includes updated results of studies with anti-CD20 therapy and other targeted therapies in the treatment of lymphomas, chronic lymphocytic leukemia, and immune thrombocytopenic purpura. The results were presented at the American Society of Hematology 44th Annual Meeting in Philadelphia, December 6 to 10, 2002.

This special supplement to Oncology NewsInternational includes updated results ofstudies with anti-CD20 therapy and othertargeted therapies in the treatment oflymphomas, chronic lymphocytic leukemia,and immune thrombocytopenic purpura. Theresults were presented at the American Societyof Hematology 44th Annual Meeting inPhiladelphia, December 6 to 10, 2002.

This special supplement to Oncology News International includes updated results of studies with anti-CD20 therapy and other targeted therapies in the treatment of lymphomas, chronic lymphocytic leukemia, and immune thrombocytopenic purpura. The results were presented at the American Society of Hematology 44th Annual Meeting in Philadelphia, December 6 to 10, 2002.

This special supplement to Oncology News International includes updated results of studies with anti-CD20 therapy and other targeted therapies in the treatment of lymphomas, chronic lymphocytic leukemia, and immune thrombocytopenic purpura. The results were presented at the American Society of Hematology 44th Annual Meeting in Philadelphia, December 6 to 10, 2002. City Hall in Philadelphia, Pennsylvania

This special supplement to Oncology News International includes updated results of studies with anti-CD20 therapy and other targeted therapies in the treatment of lymphomas, chronic lymphocytic leukemia, and immune thrombocytopenic purpura. The results were presented at the American Society of Hematology 44th Annual Meeting in Philadelphia, December 6 to 10, 2002.

It has been demonstrated that completemolecular remission in follicularlymphoma is associatedwith an improved outcome. Therefore,the object of modern therapyfor indolent lymphoma should be toachieve this goal.

PHILADELPHIA-A single four-dose cycle of rituximab (Rituxan) produced an overall response rate of 72% and median progression-free survival of 2.78 years in a phase II trial in patients with newly diagnosed, asymptomatic, advanced-stage follicular grade 1 non-Hodgkin’s lymphoma (NHL).

Dr. Nabhan and his coauthorshave written a comprehensivereview of the use of monoclonalantibodies in the treatment ofchronic lymphocytic leukemia (CLL).They have highlighted importantclinical trials with newer antibodies,including apolizumab (Hu1D10,Remitogen) and IDEC-152 (anti-CD23). The authors concisely describethe use of rituximab (Rituxan)and alemtuzumab (Campath) as singleagents and in combination therapy.Both antibodies have efficacy inthe treatment of CLL, but both havelimitations when used as singleagents.

Drs. Nabhan, Dyer, and Rosenprovide an excellent and comprehensivereview of the therapeuticrole of rituximab (Rituxan)and alemtuzumab (Campath) inchronic lymphocytic leukemia (CLL).We take this opportunity to offer ourcomments concerning these two monoclonalantibodies in CLL.

Despite many therapeutic options for chronic lymphocytic leukemia(CLL), the disease remains incurable. Since monoclonal antibodiesand recombinant toxins that bind surface antigens expressed on themalignant lymphocytes have been developed, targeted therapy hasbecome a vital option in treating CLL. Rituximab (Rituxan), a chimerichuman-mouse anti-CD20 antibody, and alemtuzumab (Campath), ahumanized anti-CD52 monoclonal antibody, have both shown activityin CLL-as single agents and in combination with conventionalchemotherapy. The possibility of combining antibodies has beenexplored as well, with some efficacy. In this review, we discuss theclinical data on the activity of commercially available antibodies inCLL, both as monotherapy and in combination with other agents.

HOLLYWOOD, Florida-There were several significant changesto the National Comprehensive CancerNetwork (NCCN) Hodgkin’s diseaseguidelines announced at the SeventhAnnual NCCN Conference (seeTable for NCCN member institutions).

ORLANDO, Florida-Addingrituximab (Rituxan) to standard chemotherapyfor follicular lymphomaregimens improves the rate and qualityof responses and increases clearanceof the bcl-2/IgH chimeric gene,according to studies from US andItalian cooperative groups reportedat the 43rd Annual Meeting of theAmerican Society of Hematology.

This special “Annual Highlights” supplement to Oncology NewsInternational is a compilation of the major advances in the managementof the lymphomas and leukemias during 2002, as reported in ONI.Commentaries by the editors, Drs. Gregory Bociek, James Armitage,and Michael Keating, provide perspective and prediction as to howthese developments may affect clinical practice.

This special “Annual Highlights” supplement to Oncology NewsInternational is a compilation of the major advances in the managementof the lymphomas and leukemias during 2002, as reported in ONI.Commentaries by the editors, Drs. Gregory Bociek, James Armitage,and Michael Keating, provide perspective and prediction as to howthese developments may affect clinical practice.

LUGANO, Switzerland-In previously untreated, advanced Hodgkin’s disease, the ChIVPP/EVA regimen, though associated with risk of sterility, is highly effective with a low incidence of secondary leukemias, according to a recent analysis of two randomized studies.

The past 30 years have seen tremendous advances in the treatment of pediatric leukemia. What was once an invariably fatal diagnosis is now quite curable in close to 80% of cases. Unfortunately for children with acute myelogenous leukemia (AML), most of these developments have been in the treatment of acute lymphoblastic leukemia (ALL); even today, nearly half of all children diagnosed with AML will die of the disease.

The use of intensive therapy over a brief period of time has produced dramatic improvements in outcome for pediatric patients with acute myelogenous leukemia (AML), as has been demonstrated in studies by the major cooperative groups in the United States and Europe. Still, despite high-intensity chemotherapy and bone marrow transplantation, only about half of the children diagnosed with AML are cured. Future improvements are unlikely to come from further increases in chemotherapy intensity. Alternative approaches, such as risk-directed therapy based on different prognostic criteria; differentiation therapy with all-trans-retinoic acid (ATRA, Vesanoid), arsenic trioxide (Trisenox), or azacytidine; and immunotherapy with monoclonal antibodies, tumor vaccines, or cytokines may lead to further advances. [ONCOLOGY 16:1057-1070, 2002]

Improvement in pediatric acute myelogenous leukemia (AML) over the past 30 years has been only modest. Although rates of complete remission induction have climbed steadily to 85% or 90%, cure rates remain in the 50% to 60% range. These figures may inspire envy from medical oncologists treating adults with AML, but they lag far behind the successes in treating pediatric acute lymphocytic leukemia (ALL).

PORTLAND, Oregon-Giving erythropoietic therapy to chronic myelogenous leukemia (CML) patients does not appear to interfere with their response to imatinib mesylate (STI571, Gleevec) therapy, according to a retrospective study of 37 patients treated in the Leukemia Center at Oregon Health and Science University in Portland (ASCO abstract 106).

In their review of the history of the management of stage I/II Hodgkin’s disease, Drs. Ng and Mauch describe the results of various treatment protocols and outline the questions posed by ongoing European, Canadian, and American trials. In a broad sense, the questions posed by these trials will help clinicians understand the benefits and complications of these treatments. However, as clinically oriented as they are, the current studies have yet to answer some common problems faced by private practitioners-the clinicians who, in North America, manage most patients with Hodgkin’s disease.

Drs. Ng and Mauch do an excellent job of summarizing the current conventional wisdom regarding the management of patients with clinical early-stage Hodgkin’s disease, although their citation of some studies is selective. Today nearly all patients with Hodgkin’s disease receive combined-modality therapy-usually an abbreviated course of a chemotherapy regimen (often one that has not been shown to cure the disease when used alone) followed by 20 to 40 Gy of involved-field radiation therapy. This approach certainly hides a multitude of sins. If you don’t give chemotherapy well, you can still achieve good disease control with the radiation therapy. If you can’t design a radiation port that encompasses known sites of disease, you can still get by because the systemic chemotherapy will leave relatively little for the radiation therapy to do.

Early-stage Hodgkin’s disease accounts for approximately 60% of all cases of the illness. Because of its excellent cure rate (80% to 90%) and high salvage rate, it is difficult to demonstrate survival advantages for