Immunoglobulin was obtained from the tumor cells of a patient with nodular lymphoma by hybridization to mouse myeloma cells. The human immunoglobulin secreted by these hybridoma cells was used as an immunogen to make murine monoclonal antibodies. Antibodies specific for idiotype, mu heavy chain and lambda light chain, were produced. One anti-idiotype antibody was used to document that idiotype-positive cells and low levels of 19S IgM idiotype were present in the patient's blood. The levels of each were found to correlate with the patient's disease activity. The monoclonal anti-idiotype was effective in eliminating idiotype-positive cells in vitro by solid phase absorption or by complement-mediated cytotoxicity. The anti-idiotype was also used to analyze the host's immunologic response to his own tumor idiotype. There was neither a detectable anti-idiotype antibody response produced in vivo nor a detectable population of T cells that expressed idiotype of could bind idiotype.
6676 HDC with HSCT is widely used in the treatment of chemosensitive relapses of NHL. There are only limited data comparing toxicities and efficacy of particular HDC regimens used in NHL. We retrospectively compared two conditioning regimens: BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan) and BuMelTT (busulphan, melphalan, thiotepa). Patients and Methods: Between January 1998 and May 2004 32 patients at a median age of 59 years (range 35–70 years) were treated with BEAM, and 54 patients (median age 51 years, range 35–65 years) with BuMelTT. Treatment groups were not significantly different with regard to histopathology and grade, sex, and former treatment, which consisted of 1 to 6 (median 3) chemotherapy regimens and a median of 9 cycles in both groups. There were significantly more patients with advanced disease (stage III and/or IV) in BEAM (81%) vs BuMelTT (58%). Radiotherapy had been given to 38% of BEAM vs 70% of BuMelTT patients. Age adjusted IPI 0–1 was diagnosed in 34% vs 47% patients, IPI 2 - 31% vs 19%, IPI 3 - 22% vs 15%, IPI 4 - 9% vs 6%, and unknown 3% vs 13% in BEAM vs BuMelT, respectively. Results: 16 of 53 (30%) patients treated with BuMelTT died, 4 due to treatment-related toxicity, one due to systemic aspergillosis, one due to stroke, and 10 (19%) of progressive disease. In contrast, 10 of 32 patients (31%) from the BEAM group died, one of treatment-related toxicity, and 9 (28%) of progressive disease. Median survival has not yet been reached, K-M estimates of 3-year OS for BEAM vs BuMelTT were 54% vs 63%, respectively. Conclusion: BEAM regimen appears less toxic than BuMelTT. It’s efficacy, however, may be inferior to BuMelTT. This observation needs to be confirmed in a randomized study. No significant financial relationships to disclose.
PURPOSE To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma. PATIENTS AND METHODS Twenty patients with relapsed low-grade (n = 15) or intermediate-/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m2 (n = 3), 250 mg/m2 (n = 7), or 375 mg/m2 (n = 10) of IDEC-C2B8. RESULTS Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urticaria. More serious events were rare. Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels. Antibody serum half-life (and maximum concentration [Cmax]) generally increased between the first and fourth infusions (33.2 hours v 76.6 hours, respectively) following the 375-mg/m2 doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 months (range, 3 to 21.7). Minor responses (MRs) were observed in five patients and progressive disease (PD) in seven. Tumor responses occurred in peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and extranodal sites, and in patients who had relapsed following high-dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded. Four of six with bulky disease had a PR. CONCLUSION IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.
'%3e%3cpath fill='%23001489' d='M0 0v6h9V0z'/%3e%3cpath fill='%23e03c31' d='M0 0v3h9V0z'/%3e%3cg stroke='%23fff' stroke-width='2'%3e%3cpath id='d' d='m0 0 4.5 3L0 6m4.5-3H9'/%3e%3cuse xlink:href='%23b' stroke='%23ffb81c' clip-path='url(%23c)'/%3e%3c/g%3e%3cuse xlink:href='%23d' fill='none' stroke='%23007749' stroke-width='1.2'/%3e%3c/g%3e%3c/svg%3e)