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OCTOBER 1999
NON-HODGKIN'S LYMPHOMA
(NHL)
Extended rituximab
therapy. Previous
trials have shown that 4 weekly doses of rituximab (anti-CD20 monoclonal
antibody; IDEC Pharmaceuticals) is effective therapy for low-grade/follicular
B-cell NHL patients who have relapsed or failed primary therapy. Recently
L.D. Piro and colleagues investigated extended rituximab therapy (8 weekly
infusions of 375 mg/m2) in a similar population of 37 NHL patients. The
extended therapy was well-tolerated, response rate (35 evaluable patients)
was 60% (14% CR and 46% PR), and the responses were durable (median time to
progression of 19.4 + months). These results show that extended rituximab
therapy is safe and the response rate is comparable to the 50% response rate
observed with the standard 4-week schedule. Further studies to determine if
extended rituximab treatment can result in greater efficacy (either overall
or in a subpopulation of B-cell NHL patients) are warranted. (Piro LD, et al.
Annals of Oncology 1999; 10: 655-661)
METASTATIC RENAL CELL
CARCINOMA (MRCC)
Tumor infiltrating
lymphocytes (TILS) plus recombinant interleukin-2 (rlL-2). Robert Figlin et al. evaluated
the antitumor activity of the combination of CD8+TlLs and low dose rlL-2
compared to rlL-2 alone (Proleukin®; Chiron Therapeutics) in a phase III
trial (n=160). No differences were found between the TlL/rlL-2 and rlL-2
groups for response rate (9.9% vs. 11.4%, respectively) or survival at 1 year
(55% vs. 47%, respectively). Thus, CD8 + TlL therapy did not augment the
effect of rlL-2 in MRCC patients after nephrectomy. (Figlin RA, et al. J Clin
Oncol 1999; 17: 2521-2529)
HEPATOCELLULAR
CARCINOMA (HCC) RISK
Interferon therapy
and chronic hepatitis C virus (HCV) patients. Haruhiko Yoshida and coworkers
followed a cohort of 2, 890 patients (a minimum of 1 year) with chronic HCV
disease who had undergone a liver biopsy since 1986. Interferon was given to
2,400 patients and 490 patients were untreated. Multivariate analysis showed
that interferon therapy was associated with a reduced risk of HCC
(P<0.001), especially among those patients who had a virologic or
biochemical response, and that the risk of HCC was increased for higher
grades of liver fibrosis. These results indicate that the risk of HCC is
reduced in chronic HCV patients responding to interferon therapy. (Yoshida H,
et al. Ann Intern Med 1999; 131: 174-181)
ACUTE LEUKEMIA
131I-anti-CD45 antibody. Targeted hematopoietic
irradiation may decrease the incidence of leukemic relapse without increasing
the toxicity associated with intensive cytotoxic therapy. Since most AML and
ALL cells express CD45, Dana Matthews et al. utilized an 131I-labeled anti-CD45 antibody combined with a
pre-bone marrow transplantation preparative regimen of high dose (120 mg/kg)
cyclophosphamide (CY) and 12 Gy total body irradiation (T131). The
radiolabeled antibody delivered estimated radiation doses to the marrow and
spleen that were 2.3 and 4.8 x greater, respectively, than that delivered to
the liver. Ten patients (7 AML/MDS and 3 ALL) who were beyond first remission
achieved prolonged disease-free survival duration (15-89 months). A maximum
tolerated dose was defined and mucositis was the dose limiting toxicity.
These data show that 131I-anti-CD45 antibody safely
delivers supplemental radiation doses to the marrow and spleen when combined
with CY/TBI. (Matthews DC, et al. Blood 1999; 94: 1237-1247)
CHRONIC MYELOID
LEUKEMIA (CML)
Leukemia-reactive
cytotoxic T lymphocytes (CTLs). JHF Falkenburg and associates report the use of
donor-derived leukemia-reactive CTLs to treat an accelerated phase CML
patient who had relapsed after allogeneic stem cell transplantation. Donor
T-cells that inhibited CML progenitor cell growth were isolated and expanded
in vitro to generate CTL lines. The CTLs were infused at 5-week intervals and
a complete remission was achieved following the third infusion (3.2 x 109 CTL
cumulative dose). This case report indicates that leukemia-reactive CTLs can
be a safe and effective therapy for accelerated phase CML. (Falkenburg JHF,
et al. Blood 1999; 94: 1201-1208)
TUMOR-SPECIFIC ANTIGENS
Human myeloma cells. Nicolas van Baren et al. used
RT-PCR to analyze 44 marrow samples from patients with multiple myeloma
(n=38) or monoclonal gammopathy of undetermined significance (MGUS) (n=6) for
the expression of MAGE-type genes. These genes encode antigens that are tumor
specific and may be important for future development of cancer immunotherapy
agents. Only one MGUS sample was positive and all samples from stage I and II
myeloma patients were negative. In contrast, the majority of samples from
stage III myeloma patients (62%) were positive for at least one of the
MAGE-type genes. These data provide a rationale to develop immunotherapy
directed at malignant plasma cells in advanced myeloma patients. (van Baren
N, et al. Blood 1999; 94:1156-1164)
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