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.
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
Risk-Adapted Dosing of Melphalan for Systemic AL Amyloidosis (AL)
Lowers Treatment-Related Mortality: Early Death but Not Post-3 Month
Survival Is Linked to Cardiac Involvement.
Comenzo, Ping Zhou, Hani Hassoun, Tarun Kewalramani,
Virginia Klimek, Adam D. Cohen, Susane K. Ferrand, Madhav Dhodapkar,
Julie Teruya-Feldstein, Martin Fleisher, Stephen D. Nimer
Chemoradiotherapy and ASCT Can Overcome the Prognostic Importance of
Bcl-2, Bim, and p53 in Relapsed/Refractory Hodgkin's Lymphoma.
Daniel Persky, Julie Teruya-Feldstein, Tarun Kewalramani,
Pauline D. Bonner, Alexia Iasonos, David Rice, Joachim Yahalom,
Stephen D. Nimer, Andrew D. Zelenetz, Craig H. Moskowitz
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.
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).
Mark A. Weiss, Joseph G. Jurcic, Suzanne Chanel, Bri-Anne Wilson, Emily
Biederman, Ellin Berman, David A. Scheinberg, Peter G. Maslak
CHEMOTHERAPY AND MONOCLONAL ANTIBODY THERAPY OF THE NON-HODGKIN'S
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,
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
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.
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
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.
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).
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
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,
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.
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
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.
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.,
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
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
Bortezomib (VELCADE™), a novel proteasome inhibitor, is effective in
refractory multiple myeloma (MM).
For the APEX Study Group
we present the interim results of an international, randomized phase 3
study conducted at 95 sites.
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.
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
Targeting of the ubiquitin proteasome pathway has proven to be a valid
and efficacious approach for the treatment of several hematologic
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
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
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
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.
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
Predictive factors to develop a second neoplasia in a Hodgkin disease
A. Rubio-Martínez, V. Recasens, C. Martos, A. Montańés, G. García-Carpintero, L.
Gómez-López, D. Rubio-Félix, P. Giraldo; Miguel Servet University
Hospital, Zaragoza, Spain; Aragon Health Service, Zaragoza, Spain
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
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