sirolimus and Lymphoma--Follicular

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Gene Targeting; Hematopoietic Stem Cell Transplantation; Humans; Indoles; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Nitrogen Mustard Compounds; Prednisone; Prognosis; Purine Nucleosides; Pyrimidinones; Risk; Rituximab; Salvage Therapy; Sirolimus; Transplantation, Autologous; Vincristine

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Feasibility Studies; Female; Follow-Up Studies; Humans; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nitrogen Mustard Compounds; Prognosis; Prospective Studies; Remission Induction; Rituximab; Safety; Sirolimus; Survival Rate

Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas.. We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas).. Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis.. Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Marrow; Chicago; Disease-Free Survival; Female; Humans; Intracellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mucositis; Pneumonia; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Remission Induction; Sirolimus; TOR Serine-Threonine Kinases; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, B-Cell; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Neoplasms, Second Primary; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Sirolimus