SCIENTIFIC RESEARCH MEETINGS

RESEARCH PRESENTED AT THE AMERICAN SOCIETY OF HEMATOLOGY (ASH) MEETING IN DECEMBER 2005

by various clinician/scientists supported in part by Lymphoma Foundation grants (names underlined)

Early Safety and Efficacy Analysis of a Phase II Study of Sequential R-CHOP and Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) for Elderly High Risk Patients with Untreated DLBCL. Paul A. Hamlin, Craig H. Moskowitz, Brett C. Wegner, Carol S. Portlock, David J. Straus, Ariela Noy, Otilia Dumitrescu, Maria Lia Palomba, Steven M. Horwitz, Owen A. O'Connor, Neeta Pandit-Taskar, Chaitanya Divgi, Andrew D. Zelenetz Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
 

Second-Line Therapy with ICE Followed by High Dose Therapy and Autologous Stem Cell Transplantation for Relapsed/Refractory Peripheral T-Cell Lymphomas: Minimal Benefit When Analyzed by Intent To Treat. Steven Horwitz, Craig Moskowitz, Tarun Kewalramani, Paul Hamlin, David Straus, Owen O'Connor, Ariela Noy, Carol Portlock, Stephen Nimer, M. Lia Palomba, Andrew Zelenetz
 

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL). Daniel Persky, Carol S. Portlock, Simone Lessac-Chenen, Alexia Iasonos, Andrew D. Zelenetz, Tarun Kewalramani, David Rice, Joachim Yahalom, Stephen D. Nimer, Craig H. Moskowitz
 

Updated Results from a Phase II Study of Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory, Follicular NHL. Jonathan W. Friedberg, John P. Leonard, Anas Younes, David C. Fisher, Leo I. Gordon, Joseph O. Moore, Myron S. Czuczman, Thomas P. Miller, Patrick J. Stiff, Bruce D. Cheson, Andres Forero-Torres, Deborah M. Finucane, Bryan R. Leigh, Arturo Molina

Initial Safety and Efficacy Results of a Second-Generation Humanized Anti-CD20 Antibody, IMMU-106 (hA20), in Non-Hodgkin's Lymphoma.  Franck Morschhauser, John P. Leonard, Bertrand Coiffier, Marie-Odile Petillon, Morton Coleman, Amina Bahkti, Puja Sapra, Nick Teoh, William A. Wegener, Ivan D. Horak, David M. Goldenberg

Pentostatin, Cyclophosphamide, and Rituximab (PCR) Has Comparable Activity but Appears To Be Better Tolerated Than Fludarabine, Cyclophosphamide, and Rituximab (FCR) in Patients with Previously Treated Chronic Lymphocytic Leukemia. Nicole Lamanna, Matt Kalaycio, Peter Maslak, Mark L. Heaney, Renier Brentjens, Joseph Jurcic, Emily Biederman, Alison N. Gencarelli, Katherine S. Panageas, David A. Scheinberg, Mark A. Weiss
 

Induction with Combined Modality Therapy Followed by Immunomodulated Post Remission Therapy for Newly Diagnosed Acute Myeloid Leukemia (AML). Seema Gupta, Mark A. Weiss, Joseph G. Jurcic, Suzanne Chanel, Bri-Anne Wilson, Emily Biederman, Ellin Berman, David A. Scheinberg, Peter G. Maslak

The ANNUAL MEETING of the AMERICAN SOCIETY OF CLINICAL ONCOLOGY -  5/13/2005 - 5/17/2005 convened in Orlando, Florida - See: web site :www.asco.org
 

SCIENTIFIC RESEARCH PRESENTED AT THE AMERICAN SOCIETY OF CLINICAL ONCOLOGISTS (ASCO) MEETING IN JUNE 2004

IN THE CATEGORY OF ADULT LEUKEMIA, LYMPHOMA and TRANSPLANTATION THERE WERE 106 ABSTRACTS OF RESEARCH  DELIVERED AS ORAL PRESENTATIONS, POSTER PRESENTATIONS OR INCLUDED ONLY AS PUBLISHED ABSTRACTS

THE FOLLOWING DATA HIGHLIGHTS SOME OF THE REPORTED STUDIES

CHEMOTHERAPY AND MONOCLONAL ANTIBODY THERAPY OF THE NON-HODGKIN'S LYMPHOMAS

Feasibility and preliminary efficacy of R-CHOP-14 in patients with diffuse large B-Cell lymphoma (DLBCL). J. L. Halaas, C. H. Moskowitz, A. Noy, C. Portlock, S. Horwitz, D. Straus, O. O'Connor, J. Yahalom, A. D. Zelenetz; Memorial Sloan Kettering Cancer Center, New York, NY

Background: Standard first line therapy for Diffuse Large B-Cell is CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Studies have shown that the addition of rituximab (R) or shortening the interval between cycles to two weeks improves survival.
Results: In total, 49 patients were included for analysis. The median age was 52 (14/49 > 60). Among evaluable patients 37/45 (82.2%) achieved a Complete Remission (CR) and 1 patient had refractory disease. Of 7 patients with refractory/relapsed disease, 4 are alive. Progression free survival at 18 months is 89%.
Conclusions: Administration of R-CHOP-14 (Rituximab-Cyclophosphamide, doxorubicin, vincristine, prednisone on a 14 day cycle) is feasible and early results show favorable efficacy. Most cycles can be delivered on time and at full dose except for VCR, which was dose-reduced in one third of cycles. Early results are encouraging and warrant comparison to R-CHOP-21 day cycle.

Durable remissions from fludarabine followed by the iodine I-131 tositumomab Bexxar therapeutic regimen for patients with previously untreated follicular non-Hodgkin’s lymphoma (NHL). J. P. Leonard, M. Coleman, L. Kostakoglu, A. Chadburn, J. M. Fiore, R. R. Furman, M. W. Schuster, S. M. Kroll, S. J. Goldsmith; Weill Medical College of Cornell University, New York, NY; Corixa Corporation, San Francisco, CA

Background: The sequential combination of chemotherapy and radioimmunotherapy offers a novel strategy for the initial management of NHL. Tositumomab and iodine I 131 tositumomab (Bexxar) have been demonstrated to have substantial clinical activity in both untreated and relapsed/refractory low-grade Non-Hodgkin’s Lymphoma. Fludarabine synergizes in vitro with unlabeled and radiolabeled antibodies and can be employed as a "debulking" agent prior to radioimmunotherapy. Patients treated: Between August 1998 and June 1999, 38 pts (51% follicular mixed, 49% follicular small cleaved) were enrolled and 97% had stage III/IV disease. Conclusions: Fludarabine followed by Bexxar therapy appeared to be a highly effective and well tolerated regimen for the initial therapy of advanced follicular Non-Hodgkin’s Lymphoma, producing long-term durable complete remissions in the majority of patients.

The iodine I-131 tositumomab therapeutic regimen: Summary of safety in 995 patients with relapsed/refractory low grade (LG) and transformed LG non-Hodgkin’s lymphoma (NHL). S. A. Gregory, J. P. Leonard, S. J. Knox, A. D. Zelenetz, J. Armitage, M. Kaminiski; Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL; Weill Medical College of Cornell University, New York, NY; Stanford School of Medicine, Stanford University, Stanford, CA; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Nebraska Medical Center, Omaha, NE; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI

Background: The Bexxar (tositumomab and iodine I 131 tositumomab [B]) therapeutic regimen yields high rates of complete and durable responses in pts with relapsed/refractory LG NHL.
Methods: The safety of B therapy was reviewed for 995 pts with relapsed/refractory Low Grade Non-Hodgkin’s Lymphoma (NHL), including 230 pts in 5 clinical trials and 765 pts in an expanded access program (EAP).
Results: Most frequent hematologic Adverse Events were grade 3/4 neutropenia (41%), thrombocytopenia (37%), and anemia (12%), requiring supportive care in 27% of patients (G-CSF, 12%; erythropoietin, 10%; platelet transfusions 12%; packed RBCs, 16%).
Conclusions: The most common Adverse Events were prolonged decrease in blood counts, but rates of hematologic sequelae were low. The data do not suggest an increased risk of Myeloid Dysplastic Syndrome or Acute Myelocytic Leukemia over that seen in patients heavily pretreated with leukemogenic therapies. The data suggested  that the risks associated with Bexxar therapy are outweighed by the clinical benefits in pts with relapsed/refractory Low Grade (LG) and transformed Low Grade non-Hodgkin’s lymphoma (NHL).

The effectiveness of tositumomab and iodine I 131 tositumomab in relapsed/refractory follicular grade 1/2 and small lymphocytic non-Hodgkin’s lymphoma (NHL). J. O. Armitage, J. P. Leonard, S. A. Gregory, S. J. Horning, A. D. Zelenetz, M. S. Kaminski, R. I. Fisher; University of Nebraska Medical Center, Omaha, NE; Weill Medical College of Cornell University, New York, NY; Rush University Medical Center, Chicago, IL; Stanford University School of Medicine, Palo Alto, CA; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; University of Rochester Medical Center, New York, NY

Background: In an overall population of 995 pts, Iodine I 131 Tositumomab was administered to 740 eligible pts with relapsed/refractory follicular grade 1/2 (n = 651) and small lymphocytic (n = 89) NHL.
Conclusions: Among 740 pts, Iodine I 131 Tositumomab produced a significantly higher Overall Remission (OR) rate and Complete Remission (CR) rate in follicular lymphoma grades 1/2 than in small lymphocytic lymphoma. However, the duration of remission was similar for responders with either diagnosis.

The addition of Rituximab to front line therapy with Cyclophosphamide, Doxorubicin, Vincristine and Predisone (CHOP) increases the remission rate and prolongs the time to treatment failure (TTF) significantly over CHOP alone in mantle cell lymphoma (MCL) – Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).  W. Hiddemann, M. Dreyling, M. Unterhalt, R. Repp, S. Hermann, A. Haenel, B. Metzner, C. Pott, F. Hartmann, R. Parwaresch; Ludwig-Maximilians-University, München, Germany

Background: Mantle Cell Lymphoma is a disease of higher age and carries a bad prognosis with a median survival of only 3 to 4 years. New treatment modalities are therefore warranted. Methods: Based on the highly encouraging results of combining Rituximab with the Fludarabine, Cyclophosphamide, Mitoxantrone (FCM) regimen for salvage therapy of relapsed MCL, the German Low Grade Lymphoma Study Group embarked on a prospective randomized trial comparing CHOP versus Rituximab plus CHOP (R-CHOP) for first line therapy. 122 consecutive patients with newly diagnosed Mantle Cell Lymphoma of stages III and IV were randomized between CHOP versus R-CHOP.
Conclusions: R-CHOP induces remissions in almost all patients with previously untreated MCL and prolongs the time to treatment failure significantly over CHOP alone. R-CHOP is a highly effective, well tolerated regimen for front line therapy of Mantle Cell Lymphoma.

BORTEZOMIB (VELCADE) PROTEASOME INHIBITOR THERAPY IN MULTIPLE MYELOMA

First-line therapy with bortezomib (formerly PS-341) in patients with multiple myeloma (MM). S. Jagannath, B. Durie, J. Wolf, E. Camacho, D. Irwin, J. Lutzky, M. McKinley, E. Gabayan, J. Crowley, D. P. Schenkein; St. Vincent's Comprehensive Cancer Center, New York, NY; Salick Health Care Research Network, Los Angeles, CA; Cancer Research and Biostatistics, Seattle, WA; Millennium Pharmaceuticals, Inc., Cambridge, MA

Background: Preclinical evidence has suggested that the proteasome is an effective therapeutic target in MM. Clinical trials have since demonstrated the durable efficacy and safety of bortezomib (Velcade), a potent reversible proteasome inhibitor, recently approved for the treatment of pts with refractory and relapsed Multiple Myeloma.
Conclusions: In this study, bortezomib appeared to be promising as initial therapy in patients with newly diagnosed Multiple Myeloma and had manageable toxicities. Major responses (near Complete Remissions and Partial Remissions) were seen in 75% of the patients by 6 cycles of therapy. Study accrual is ongoing, and the full complement of 42 pts is expected to be recruited quickly.

Bortezomib vs. Dexamethasone in Relapsed Multiple Myeloma: A phase 3 randomized study. P. Richardson, P. Sonneveld, M. W. Schuster, D. Irwin, E. A. Stadtmauer, T. Facon, W. S. Dalton, J. Harousseau, J. F. San Miguel, K. C. Anderson; Dana-Farber Cancer Institute, Boston, MA; University Hospital Rotterdam, Rotterdam, Netherlands; New York Presbyterian Hospital, New York, NY; Alta Bates Cancer Center, Berkeley, CA; U. Pennsylvania Cancer Center, Philadelphia, PA; Hospital Claude Huriez, Lille, France; H. Lee Moffitt Cancer Center, Tampa, FL; Hotel Dieu Hospital, Nantes, France; Hospital Universitario de Salamanca, Salamanca, Spain

Background: Bortezomib (VELCADE™), a novel proteasome inhibitor, is effective in refractory multiple myeloma (MM).
Methods: For the APEX Study Group we present the interim results of an international, randomized phase 3 study conducted at 95 sites.
Conclusions: Bortezomib was significantly more effective than dexamethasone for patients with relapsed Multiple Myeloma. Further evaluation of survival, response duration, response rate, and safety are ongoing.

BORTEZOMIB (VELCADE) PROTEASOME INHIBITOR THERAPY IN THE LYMPHOMAS 

Marked clinical activity of the novel proteasome inhibitor bortezomib in patients with relapsed follicular (RL) and mantle cell lymphoma (MCL). O. A. O'Connor; Memorial Sloan Kettering Cancer Center, New York, NY

Background: Targeting of the ubiquitin proteasome pathway has proven to be a valid and efficacious approach for the treatment of several hematologic malignancies.
Methods/Results: To date, we have treated 25 previously treated patients with relapsed or refractory indolent lymphomas, including: 3 patients with small lymphocytic lymphoma; 9 patients with Follicular Lymphoma; 11 patients with Mantle Cell Lymphoma; and 2 patients with marginal zone lymphoma. All but one patient had received some form of treatment prior to receiving bortezomib Conclusions: The responses to bortezomib continue to support the biological activity of bortezomib in patients with select sub-types of indolent Non-Hodgkin’s Lymphoma.

Update on a phase (ph) 2 study of bortezomib in patients (pts) with relapsed or refractory indolent or aggressive non-Hodgkin’s lymphomas (NHL). A. Goy, A. Younes, P. McLaughlin, B. Pro, J. Romaguera, F. Hagemeister, L. Fayad, E. G. Trehu, D. Schenkein, M. A. Rodriguez; The University of Texas M. D. Anderson Cancer Center, Houston, TX; Millennium Pharmaceuticals, Inc., Cambridge, MA

Background: Proteasome inhibition disrupts many cell cycle checkpoints and pathways that lead to apoptosis. Preclinical and phase 1 studies suggested the proteasome inhibitor bortezomib (VELCADE™) was active in lymphoma.
Patients treated:45 pts: 32 males, 13 females, median age 60 yr (range 45-81), were enrolled. Conclusions: This study showed remarkable activity of Velcade in refractory or relapsed Mantle Cell Lymphoma and encouraging results in other B cell lymphomas. Future studies will include combinations of Velcade with other chemotherapy and/or biological agents.

LATE ONSET SECOND MALIGNANCIES AFTER RADIATION TREATMENT FOR HODGKIN’S DISEASE

Relative risk (RR) of second malignancies (SM) in patients treated by "risk" radiotherapy (RT) or "risk" RT plus chemotherapy (CT) in comparison with patients treated by CT ± "non risk RT" for Hodgkin's disease (HD). K. Petrakova, H. Koukalová, R. Soumarová, M. Palácová, S. Blakova, R. Vyzula; Masaryk Memorial Cancer Institution, Brno, Czech Republic

Background: Late effect, in particular second malignancies, kill more patients with HD then the disease itself.
Methods: 851 patients (475 men and 376 women) with survival time after HD diagnosis >1 year were treated in MOÚ during 1967-1995. 337 patients were treated only by RT, 182 only by CT and 332 by RT+CT. Median age at RT was 33 years, median follow-up 11 years. 74 cases of SM developed in the cohort.
Results: Relative Risk (RR) for the Second Malignancies were as follows: breast cancer 5.39; lung cancer 0.77; colorectal cancer 10.3; stomach cancer 1.46; thyroid cancer 1.18; gynecologic cancer 2.19.  
Conclusion: The relative risk of solid tumors as second malignancies increased with the time of follow-up. Treatment by "risk RT" increases the Relative Risk of breast cancer, colorectal cancer, gynecologic cancer and slightly thyroid cancer. Therefore this group of patients should be offered more intensive follow-up : yearly breast examination (Mammography), yearly hemoccult stool testing, colonoscopy every 3 years, and yearly gynecologic examination because of the risk of Second Malignancies.

Predictive factors to develop a second neoplasia in a Hodgkin disease cohort patients. A. Rubio-Martínez, V. Recasens, C. Martos, A. Montañés, G. García-Carpintero, L. Gómez-López, D. Rubio-Félix, P. Giraldo; Miguel Servet University Hospital, Zaragoza, Spain; Aragon Health Service, Zaragoza, Spain

Background: Hodgkin’s lymphoma (HL) is a rare malignancy but the importance of late effects of therapy have become more apparent.
Methods: a cohort of 295 patients diagnosed as having in the Hematology Department of Miguel Servet University Hospital was followed-up (population at risk: 533,946).
Conclusions: The incidence of Second Malignancies among long-time survivors of Hodgkin’s Lymphoma is higher than in normal population.

GO TOP or REVIEW DATA FROM OTHER MEETINGS and PUBLICATIONS

  CONTACT  US

The Lymphoma Foundation is a nationwide not for profit foundation dedicated to funding clinical and basic laboratory cancer research and applying the knowledge developed by the clinician scientists for the general welfare and education of all cancer patients. 

© Copyright 2006 THE LYMPHOMA FOUNDATION All rights reserved