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Phase I trial of temsirolimus and lenalidomide in pts with rel/ref lymphomas.
Lymphoma and Plasma Cell Disorders
Session Type and Session Title:
General Poster Session, Lymphoma and Plasma Cell Disorders
J Clin Oncol 30, 2012 (suppl; abstr 8075)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: The PI3K/Akt/mTOR axis is deregulated in lymphomas and is an emerging therapeutic target. We previously reported activity of temsirolimus (TEM) in DLBCL and FL (JCO 2010 28(31); however, the response duration was short. Lenalidomide (LEN) is an immunomodulatory agent with multiple anti-tumoral and microenvironmental effects, with activity across lymphoma subtypes. We are thus conducting a phase I/II study of TEM plus escalating doses of LEN. The phase I portion is completed. Methods: Patients (pts) had rel/ref lymphoma after >1 cytotoxic regimen. Other criteria: ANC > 1000/mL, platelets > 75,000/mL, nl renal and hepatic function, no VTE within 3 months, non-pregnant. A standard “3 + 3” design was used with dose levels (DL) listed (Table). TEM was given IV weekly and LEN was dosed orally on D1-D21, q28 days. Dose-limiting toxicity (DLT) was defined as cycle 1 grade 3 or 4 non-hematologic toxicity not responsive to standard supportive care, grade 4 thrombocytopenia > 7 days (or associated with bleeding or requiring more than 1 platelet transfusion), ANC < 500/mL > 7 days despite growth factors, or any thromboembolic event. Results: 18 pts (13M, 5F), med age 64 y (range, 42-80 y) were enrolled. 3 pts are ineval for DLT evaluation: one withdrew consent before starting treatment, 1 withdrew consent after a single dose, and 1 died of rapid disease progression after 1 dose. There was 1 DLT at DL1 and 2 DLTs at DL3 (Table). Adverse effects that did not meet DLT criteria: hypokalemia, hypertriglyceridemia, vomiting, urinary tract infection, skin infection, nausea, hypoxia, hyponatremia, diarrhea, and hyperglycemia (each occurring in one pt). There are 5 partial responses, 4 stable disease, 3 progressive disease, 2 not adequately assessed, and 4 still on active treatment. Conclusions: The combination of weekly intravenous TEM plus oral LEN is well-tolerated in a heavily pretreated group of pts with rel/ref lymphomas. The recommended phase II doses are TEM 25mg weekly plus LEN 20mg (D1-D21, q28d).
(flat dose in mg)
(flat dose in mg)
|-1||25 mg||10 mg||n/a||n/a|
|1||25 mg||15 mg||8 (2 ineval for DLT)||Grade 4 hypokalemia|
|2||25 mg||20 mg||4 (1 ineval for DLT)||No DLT|
|3||25 mg||25 mg||6||Grade 3 diarrhea, grade 3
Abstracts by Sonali M. Smith:
Association of reduced intensity conditioning (RIC) allograft (alloHCT) as first transplant approach in relapsed/refractory grade 3(G-3) follicular lymphoma (FL) with improved outcomes in long-term survivors.Meeting: 2015 ASCO Annual Meeting | Abstract No: 7009
Early rituximab failure (ERF) in relapsed diffuse large b-cell lymphoma (DLBCL) and prediction of futility of autologous hematopoietic cell transplantation (AHCT).Meeting: 2014 ASCO Annual Meeting | Abstract No: 7048
Peripheral T-cell lymphomas (PTCL) in the modern era: Prognosis and impact of therapy in a large U.S. multicenter cohort.Meeting: 2014 ASCO Annual Meeting | Abstract No: e19561