Biomedical subjects

P S Multani

Publications and source records attributed to P S Multani.

4 recordsLinked to original sources

PubMed1999

A Phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma.

This Phase II trial was undertaken to determine the safety, toxicity, and potential efficacy of the B-cell restricted immunotoxin anti-B4-blocked ricin (Anti-B4-bR) when administered as adjuvant therapy to patients in complete remission (CR) after autologous bone marrow transplantation (ABMT) for B-cell non-Hodgkin's lymphoma (NHL). Forty-nine patients with B-cell NHL in CR 46-202 days (median, 112 days) post-ABMT received Anti-B4-bR at a dose of 30 microg/kg lean body weight/day for 7 days by continuous i.v. infusion. Patients were eligible for up to two additional courses of therapy at 14-day intervals. A total of 83 courses of Anti-B4-bR were administered, with 31 patients receiving two or more courses of therapy. The mean serum level on day 7 of the first course was 0.77+/-0.41 nM. Reversible toxicities included hepatic transaminase elevations, thrombocytopenia, myalgias, fatigue, nausea, hypoalbuminemia, and dyspnea. Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) responses occurred in 23 patients at a median of 22 days from the initiation of Anti-B4-bR therapy (range, 11-100 days). The 4-year disease-free survival and overall survival are estimated at 56 and 72%, respectively. Twenty-six patients remain in CR after a median follow-up of 54.5 months. This study demonstrates that Anti-B4-bR can be administered safely to patients as adjuvant therapy early after ABMT for B-cell NHL. The toxicities are tolerable and reversible. Although the early estimate of disease-free survival was very encouraging in this single-armed trial, the 4-year follow-up data demonstrate continued relapse.

Adult↗

PubMed1999

Melanoma.

In melanoma, conventional therapies, especially cytotoxic chemotherapies, have proven unsatisfactory. Although a variety of agents have been tested singly and in combination, recent randomized studies have demonstrated that the response rates observed in single institution phase II trials are not generalizable to multi-institution settings. Studies of cytokine therapy, especially interferon-alpha in the adjuvant situation, and interleukin-2 for advanced disease, have demonstrated some utility to these agents. However, their toxicities remain formidable, and studies refining their use are under way. The limited successes of such immunomodulatory strategies have provided a rationale for continued pursuit of immunotherapy approaches. It is likely that in the near future such active immunization protocols will continue to be actively investigated.

Chemotherapy, Adjuvant↗

PubMed1998

Monoclonal antibody-based therapies for hematologic malignancies.

PURPOSE: To review recent advances in the development and clinical roles of monoclonal antibody (MoAb)-based therapies in the treatment of hematologic malignancies. DESIGN: A search of MEDLINE and CANCERLIT was conducted to identify relevant publications. The bibliographies of these references also were used to identify articles and abstracts. These references were then reviewed. RESULTS: In the two decades since the first patient was treated with MoAb therapy, there have been significant advances in the biology, pharmacology, and clinical application of MoAb-based therapies. Three distinct fields of research have emerged: unconjugated MoAbs, immunotoxin-conjugated MoAbs (ITs), and radionuclide-conjugated MoAbs (RICs). The unconjugated MoAbs are less toxic but depend on host mechanisms to mediate cytotoxicity. The ITs carry a potent toxin, although at the cost of a narrow therapeutic index that may limit clinical use. The RICs offer significant potency, even in refractory disease, but their complexity may limit their use to large cancer centers. The current challenges in the development of MoAb-based therapies are to identify the proper target antigens, contend with bulk disease in which penetration may be limited, and choose the optimal clinical settings for their use, such as the minimal residual disease state or in combination with conventional chemotherapy. CONCLUSION: Although significant research is still needed, MoAb-based therapies promise to offer new options for the treatment of patients with hematologic malignancies.

Animals↗

PubMed1998

Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma.

Immunotoxins, composed of a monoclonal antibody conjugated to a protein toxin, mediate cell death through novel cytotoxic mechanisms. Anti-B4-blocked ricin (anti-B4-bR) recognizes CD19-positive cells, which includes most B-cell non-Hodgkin's lymphomas (NHLs). Previous Phase I clinical studies of anti-B4-bR, using both bolus and continuous dosing regimens, demonstrated no safety or efficacy advantage to the continuous infusion regimen. This Phase II trial in 16 patients with relapsed CD19-positive NHL was conducted to evaluate the efficacy of anti-B4-bR when administered at the previously established maximum tolerated dose using a daily bolus for a 5 consecutive days schedule. Serum pharmacokinetics were measured in selected patients. Tissue samples of involved lymph nodes and bone marrow were also obtained from a portion of patients for determination of anti-B4-bR penetration into tissues. Toxicity was similar to what has been described previously for anti-B4-bR and consisted mainly of reversible elevations of hepatic transaminases and mild to moderate thrombocytopenia. No sustained clinical responses were documented. Pharmacokinetic measurements demonstrated that serum levels compatible with 3 logs of cell kill in vitro could be sustained for several hours in most patients. Immunohistochemical analysis of tissue samples provided some insight into the low efficacy. The immunotoxin could be detected in three of the four bone marrow aspirate samples but in only two of the seven lymph node specimens. Thus, anti-B4-bR, using a single daily bolus for a 5 consecutive day schedule, is not an active agent in relapsed NHL. Poor penetration into certain sites of disease may be one explanation for its lack of efficacy.

Adult↗