BioOncology Watch Timely Information for Practicing Physicians
march 2001 Non-Hodgkin’s Lymphoma (NHL) First line rituximab (anti-CD20 monoclonal antibody therapy). Philippe Colombat and associates report results from a multicenter phase II study in which rituximab (MabThera; Produits Roche, Neuilly France) at a dose of 375 mg/m^2/week for four weeks was evaluated as single-agent first-line therapy for patients with follicular NHL with low tumor burden. Fifty patients were enrolled and 49 patients were evaluable for response. One month after treatment (Day 50) the response rate was 73% (36 of 49). These responses included 10 patients in complete remission (CR), 3 in complete remission/unconfirmed (CRu), and 23 in partial remission (PR). In 10 patients (28%) there was disease progression in the first 12 months of follow-up (1 CR/CRu, 9 PRs). Day 50 polymerase chain reaction (PCR) analyses showed that 17 of 30 patients (57%) and 9 of 29 patients (31%) were negative for bcl-2-JH rearrangement in peripheral blood and bone marrow, respectively. After 12 months, 16 of 26 patients (62%) remained PCR negative in peripheral blood. An association between molecular and clinical responses was observed (p<0.0001). These early results indicate that rituximab is effective first-line treatment for follicular NHL patients with low tumor burden and that molecular responses can be sustained for at least 12 months. (Colombat P, et al. Blood 2001;97:101-106) Rituximab in combination with CHOP. JM Vose and colleagues investigated the combination of rituximab (IDEC Pharmaceuticals) therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Thirty-three previously untreated patients with advanced aggressive B-cell NHL (International Working Formulation types D to H) were treated with 6 cycles of intravenous rituximab (375 mg/m^2 given on Day 1 of each 21-day cycle) plus intravenous cyclophosphamide 750 mg/m^2, doxorubicin 50 mg/m^2, and vincristine 1.4 mg/m^2 given on Day 3 and oral prednisone 100 mg given on Days 3 through 7. The objective response rate was 94%, which included 20 patients (61%) who experienced a CR and 11 patients (33%) who had a PR. The median duration of response as well as the median time-to-progression of disease had not been reached after a median follow-up of 26 months. In addition, all 11 patients studied who had blood or bone marrow specimens positive for the bcl-2 translocation at baseline achieved a negative bcl-2 status after therapy by PCR assay. One patient reconverted to bcl-2 positivity, however all 11 patients remained in clinical remission. At the 42^nd annual ASH meeting, B. Coiffier presented the interim analysis of a randomized study comparing standard CHOP chemotherapy to CHOP plus rituximab 375 mg/m^2 in patients with stage II-IV diffuse large B-cell lymphoma in which 76% of patients in the R-CHOP group had complete remissions vs 60% in the CHOP group, 69% of the R-CHOP group had 12-month event-free survival vs 49% in the CHOP group, and 83% of the R-CHOP group had 12-month overall survival vs 68% in the CHOP group. Randomized phase III trials in the U.S. comparing rituximab plus CHOP to CHOP alone are ongoing to establish the clinical benefits of R-CHOP in patients with advanced NHL. (Vose JM, et al. J Clin Oncol 2001;19:389-397) Multiple Myeloma (MM) Meta-analysis of interferon (IFN) trials. MM was the first malignancy shown to be sensitive to IFN. However, subsequent randomized trials yielded inconsistent results and after 2 decades of clinical investigation there is no definitive proof that IFN therapy is beneficial for patients with MM. E. Fritz and H. Ludwig performed a meta-analysis of published data of randomized trials investigating the effectiveness of IFN treatment in MM patients. This analysis includes 17 trials in which patients received IFN-chemotherapy vs. chemotherapy alone for induction treatment (n=2,333) and 13 trials in which patients received IFN maintenance therapy vs. no further therapy (n=1,615). Patients who received IFN-chemotherapy induction treatment had a 6.6% higher response rate (p <0.002), a 4.8-month greater relapse-free survival (p <0.01), and a 3.1-month greater overall survival (p <0.01). Patients who received IFN maintenance therapy had a 4.4-month greater relapse-free survival (p <0.01) and a 7.0-month greater overall survival (p <0.01). Analysis of all the IFN trials combined demonstrated 4.6-month and 3.7-month gains in relapse-free and overall survival, respectively, for IFN-treated patients. IFN drug costs for a 1-year survival gain were estimated to be $42,482 (US) for induction therapy and $18,968 (US) for maintenance therapy. These findings are consistent with those of a meta-analysis of individual patient data conducted by the Myeloma Trialists' Collaborative Group and indicate that IFN therapy results in moderate survival gains for MM patients at feasible costs, but with substantial toxicity. (Fritz E and Ludwig H. Ann Oncol 2001;11:1427-1436) Pancreatic Cancer Phase I trial of a tumor vaccine. Autologous granulocyte-macrophage colony-stimulating (GM-CSF)-secreting tumor vaccines have have shown promising results in preliminary human clinical trials. Elizabeth Jaffee and associates at The Johns Hopkins Medical Institutions conducted a phase I trial of a novel allogeneic GM-CSF-secreting tumor vaccine (prepared from pancreatic tumor cell lines) in patients with surgically resected adenocarcinoma of the pancreas (n=14). Serial cohorts of patients were vaccinated with increasing doses of the vaccine 8 weeks after pancreaticoduodenectomy (3 patients each received 1, 5, and 10 x 107 vaccine cells and 5 patients received 50 x 107 vaccine cells). Twelve of 14 patients also received a 6-month course of adjuvant radiation and chemotherapy. Six of these patients who were still in remission following adjuvant therapy were given up to 3 additional monthly vaccinations. No dose-limiting toxicities were observed and delayed-type hypersensitivity (DTH) responses to autologous tumor cells were induced in 3 patients who received (10 x 107 vaccine cells. These 3 patients have remained disease-free 25 months after diagnosis. GM-CSF-secreting tumor vaccine was found to induce a dose-dependent DTH response against autologous pancreatic tumor and further clinical evaluation is warranted. (Jaffee EM, et al. J Clin Oncol 2001;19:145-156)
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