Cancer Treatment Today

Lay Summary: Revlimid is promising for CLL.

Revlimid is an orally administered derivative of thalidomide, which is a very active agent for the treatment of multiple myeloma but has serious side effects, especially thromboembolism. Revlimid is reported to have less toxicity than thalidomide but retains antimyeloma effects. Revlimid has recently been approved by the FDA for review of treatment of myelodysplastic syndromes (MDS) wih a 5q- mutation and for first line treatment of multiple myeloma in conjunction with dexamethasone. Revlimid is in clinical trials for the evaluation of treatment for other hematologic cancers including CLL.

There are many studies supporting effectiveness of Revlimid, although most of them are small and presented in the abstract form.

Researchers from the Roswell Park Cancer Center and the Toronto Sunnybrook Regional Cancer Center have reported that Revlimid has significant activity in CLL. This study was also presented at the 2005 meeting of the American Society of Hematology in December 2005. Thalidomide has also demonstrated activity when combined with Fludara for initial treatment of CLL. This was a small study involving only 16 patients, but the complete response rate was over 50%.

The study presented at ASH 2005 and ASCO 2006 involved 29 patients with relapsed or refractory CLL. More than 50% has failed Rituxan combinations and more than 50% had failed fludarabine combinations. The complete response rate was 15%, the partial response rate was 53% and an additional 15% had stable disease. Two patients had complete molecular responses. The most common side effects reported were fatigue, neutropenia and thrombocytopenia. Approximately 60% had “flare reaction”—described as tender swelling of lymph nodes and rash—which was successfully treated with steroids. In-vitro studies showed an increased number of natural killer cells but no increase in apoptosis.

In 2008, Celgene reported two REVLIMID (lenalidomide) Phase II studies at the 50th American Society of Hematology Meeting. Both demonstrated high response rates and manageable side effects in patients previously untreated with symptomatic chronic lymphocytic leukemia (CLL). The studies demonstrated greater than 90 percent disease control across all evaluable patients. In 2009, at ASH, there was presented a phase II study of Rituxan. Revlimid combination conducted at MD Anderson Cancer Center demonstrated a 64 percent overall response after 12 cycles, including the observation of complete responses. In 2008, at ASH, there was presented a phase II study of Rituxan. Revlimid combination conducted at MD Anderson Cancer Center demonstrated a 64 percent overall response after 12 cyces, including the observation of complete responses.

It is also listed by the Drugdex compendium for CLL. The most recent noteworthy paper was in Blood 2011. Sixty patients with CLL age 65 years and older received treatment with lenalidomide orally 5 mg daily for 56 days, then titrated up to 25 mg per day as tolerated. Treatment was continued until disease progression. At a median follow-up of 29 months, 53 patients (88%) are alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free survival is 60%. The overall response rate to lenalidomide therapy is 65% including 10% complete response, 5% complete response with residual cytopenia, 7% nodular partial response, and 43% partial response. These are very good results for the limited reported toxicity in the ederly population.

Miller K, Czuczman MS, Dimicli L, et al. Lenalidomide (L) induces high response rates with molecular remission in patients (pts) with relapsed (rel) refractory (ref) chronic lymphocytic leukemia (CLL). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, Ga. 2006. Abstract # 6605.

Chanan-Khan AA, Miller KC, DiMicheli L, et al. Results of a phase II study of lenalidomide (L) (Revlimid) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Blood 2005;135a, abstract # 447.

Chanan-Khan A, Miller KC, Takeshita K, et al. Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL). Blood. 2005;106:3348-3352.

Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. Journal of Clinical Oncology. 2006;24:5343-5349.

Chen C, Paul H, Xu W, et al. A phase II study of lenalidomide in previously untreated, symptomatic chronic lymphocytic leukemia (CLL). Blood. 2008;112:23, abstract number 44.

Kornblau SM, Burger JA, Ferrajoli A.et al, Lenalidomide (REVLIMID) as initial therapy of elderly patients with chronic lymphocytic leukemia.Blood. 2011 Jul 1.