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
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 8075)
Sonali M. Smith, Kenneth Stuart Cohen, Justin Paul Kline, Jose D Zavala, Kathy Conner, Sachdev P Thomas, Patricia Lesho, Laurence A. Doyle, Walter Michael Stadler, Theodore Karrison, Amy Sarah Kimball; The University of Chicago, Chicago, IL; University of Chicago, Chicago, IL; Illinois Cancer Care, Peoria, IL; University of Maryland, Baltimore, MD; National Cancer Institute, Rockville, MD

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Abstract Disclosures


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).
Dose level Dose
No. Pts DLT
(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
HSV mucositis