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BioOncology Watch Timely Information for Practicing
Physicians |
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march 2000 Non-Hodgkin’s Lymphoma (NHL) Rituximab treatment: a European experience. James Foran et al. report the results of a European phase II
trial (n=131) in which patients with newly diagnosed mantle cell lymphoma
(MCL; n=34), previously treated MCL (n=40), immunocytoma (IMC; n=28) or small
B-cell lymphocytic lymphoma (SLL; n=29) were treated with rituximab 375 mg/m2
weekly IV x 4. The response rate (CR
+ PR) among 120 evaluable patients was 30%.
There were 10 CRs, all of which occurred in MCL patients. By histology the response rates were: newly diagnosed MCL, 38%; previously
treated MCL, 37%; IMC, 28%; SLL, 14%.
Rituximab infusions were well tolerated, however 10 patients
experienced cardiac arrhythmias and 9 patients developed ocular toxicities
(conjunctivitis, burning sensation, transient edema, or transient visual
changes). The results show rituximab
has moderate activity in MCL and IMC but little effect in SLL. Trials testing rituximab in combination
with cytotoxic chemotherapy in MCL and IMC are warranted. (Foran JM, et al. J Clin Oncol 2000; 18: 317-324) Leukemia
Adoptive immunotherapy to prevent relapse of acute
leukemia. P. Bader et al.
recently presented evidence that autologous marrow repopulation, as demonstrated
by an increasing mixed chimerism, is an early indicator of an enhanced risk
of acute leukemia relapse (P <0.0001) in children following the
achievement of CR after allogeneic stem cell transplantation (SCT). They now describe the results of a pilot
study in which withdrawal of immunosuppression and /or donor lymphocyte
infusions (DLI) were utilized to treat 12 acute leukemia/myelodysplastic
syndrome (MDS) pediatric patients (5 ALL, 3 AML, 4 MDS) who developed
increasing mixed chimerism post-transplant.
Complete chimerism was re-established in 4 patients by withdrawal of
cyclosporine and in another 6 patients by DLI. The 2 patients who did not respond developed hematologic
relapse and died prior to the initiation of further therapy. These results suggest adoptive
immunotherapy may be a useful modality to prevent relapse in children with
acute leukemias or MDS after allogeneic SCT.
(Bader P, et al. Leukemia
1999; 13: 2079-2086) Persistence of BCR-ABL rearrangement in chronic
myeloid leukemia (CML).
Jean-Claude Chomel and colleagues evaluated minimal residual disease
(MRD) in 21 CML patients who had a complete cytogenetic response (CCR) by
conventional cytogenetic analysis following allogeneic bone marrow transplantation
or treatment with interferon a. Southern blot analyses were negative or
only weakly positive while the more sensitive fluorescent in site
hybridization (FISH) methods detected the BCR-ABL gene rearrangement in all
21 patients (1%-12% of nuclei).
Quantitative reverse transcription-polymerase chain reaction
(Q-RT-PCR) analyses were also negative or weakly positive, however this
technique detected a rising BCR-ABL/ABL ratio 2 months prior to relapse in
the one patient who did develop cytogenetic evidence of disease during follow-up. FISH techniques detect gene abnormalities
in dormant as well cycling cells and these results suggest that the
persistence of nonproliferating malignant cells is common in CML patients in
CCR. Also, Q-RT-PCR may be a valuable
test to detect such cells as they re-enter the cell cycle. (Chomel J-C, et al. Blood 2000; 95: 404-409) CD38 ligation. CD38 is a transmembrane molecule expressed
during lymphohematopoietic cell differentiation. Elisabetta Todisco and coworkers recently investigated the
effect of CD38 ligation on normal and leukemic myelopoiesis. CD34+ cells
(>90% of which are CD38+) were separated from normal bone marrow and cord
blood and from the bone marrow of 7 patients (age 7 to 15 years) with newly
diagnosed acute myeloid leukemia. The
CD34+ cells were then grown in bone marrow-derived stromal cultures. The addition of monoclonal anti-CD38
antibodies (T16) to the cultures of normal CD34+ cells induced a reduction of
the mature myeloid cell population (promyelocytes, myelocytes, metamyelocytes). CD38 ligation also suppressed the recovery
of cells from the leukemia myeloid cell cultures (mean cell recovery of 25.2%
on ± 21.7%
of control cultures). Moreover, CD38
ligation suppressed the recovery of murine 32D myeloid cells transfected with
human CD38 to 3.8% ± 7.3%
(n=7) of control cultures. These data
show that CD38 activation mediates suppression of myeloid cell growth of
normal and patient-derived leukemic cells in coculture with marrow stroma. (Todisco E, et al. Blood 2000) Vaccines
Anti-idiotype vaccine for melanoma. Kenneth Foon and coworkers vaccinated 47
advanced melanoma patients with escalating doses of an anti-idiotype
antibody, TriGem (Titan Pharmaceuticals Inc.), mixed with Q5-21 adjuvant
(Aquila Biopharmaceuticals Inc.).
TriGem mimics disialoganglioside GD2, which is highly expressed on the
surface membranes of melanoma cells.
All 40 patients who continued in the study for at least 3 months generated
anti-disialoganglioside GD2 antibody responses (predominately IgG). One patient had a CR and 12 patients had
stable disease for a median of 18 months.
More importantly, median survival had not yet been reached. Side effects were limited to mild fever
and chills and local swelling at the injection site. These data show that TriGem therapy is
well tolerated, generates a specific IgG immune response, and may have a
favorable impact on survival in patients with advanced melanoma. These outcomes warrant further studies. (Foon KA, et al. J Clin Oncol 2000; 18: 376-384) |
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