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(Chest. 2002;121:1921-1927.)
© 2002 American College of Chest Physicians

Intrapleural Infusion of Activated Macrophages and {gamma}-Interferon in Malignant Pleural Mesothelioma*

A Phase II Study

Isabelle Monnet, MD; Jean-Luc Breau, MD; Denis Moro, MD; Hervé Lena, MD; Jean-Christophe Eymard, MD; Olivier Ménard, MD; Jean-Philippe Vuillez, MD; Mohamed Chokri, PhD; Jean-Loup Romet-Lemonne, MD and Manuel Lopez, MD, FCCP

* From the Department of Pneumology (Dr. Monnet), Center Hospitalier Intercommunal de Créteil, Créteil; the Department of Oncology (Dr. Breau), Hôpital Avicenne, Bobigny; Department of Pneumology (Dr. Moro), Center Hospitalo-Universitaire, Grenoble; Department of Pneumology (Dr. Lena), Hôpital Pontchaillou, Rennes; Institut Jean Godinot (Dr. Eymard), Reims; Department of Pneumology (Dr. Ménard), Hôpital de Brabois, Vandoeuvre-les-Nancy; Service de Médecine Nucléaire (Dr. Vuillez), Center Hospitalo-Universitaire, Grenoble; Immuno-Designed Molecules (Drs. Chokri and Romet-Lemonne), Paris; and Inserm U76 (Dr. Lopez), Laboratoire de Thérapie Cellulaire, Faculté de Médecine Saint Antoine, Paris, France.

Correspondence to: Manuel Lopez, MD, FCCP, Laboratoire de Thérapie Cellulaire, Faculté de Médecine Saint Antoine, 27 rue de Chaligny, 75012 Paris, France; e-mail: manuel.lopez{at}chusa.jussieu.fr

Study objectives: Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AM{Phi}) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM).

Design: AM{Phi} derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of {gamma}-interferon ({gamma}-IFN) in an attempt to prolong the in vivo activation of infused AM{Phi}. Response was assessed by CT scan and thoracoscopy when possible. If the patient’s disease progressed after AM{Phi} treatment, an additional treatment was left to the choice of the investigator.

Patients: Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AM{Phi} infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AM{Phi} cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed.

Results: The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AM{Phi} or {gamma}-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AM{Phi}, was 29.2 months.

Conclusion: Combined infusion of AM{Phi} and {gamma}-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity.

Key Words: activated macrophages • intrapleural immunotherapy • malignant pleural mesothelioma




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