Tag: rituximab

Lymphoma in the news: Cyclophosphamide may be associated with an increased risk of secondary myeloid neoplasia when administered with fludarabine to patients with chronic lymphocytic leukemia

By Peter Martin, MD

The US Intergroup Trial E2997 was a phase 3 trial comparing two first-line chemotherapy regimens in patients with previously untreated chronic lymphocytic leukemia (CLL). A total of 278 patients were randomized to receive fludarabine (F) or fludarabine plus cyclophosphamide (FC) (click here to read the abstract). Consistent with a German CLL Study Group (GCLLSG) Trial (see abstract here), the results demonstrated that FC was associated with higher overall and complete response rate.

Importantly, neither E2997 nor the GCLLSG trial found a difference in overall survival despite the improvement in response rates. Since then, FC has been replaced by FCR (FC plus rituximab) on the basis of even better response rates demonstrated in subsequent trials. The role of cyclophosphamide in the FCR regimen, however, has been somewhat controversial. On the basis of historical comparison between trials, proponents of FCR suggest that it likely induces higher response rates than FR, especially in the group of patients deletion of the 11q (a common chromosomal abnormality in CLL cells). Other investigators point out that cyclphosphamide is a toxic chemotherapy drug that has never demonstrated an ability to improve overall survival.

Adding to this controversy is a recent publication. Dr. Mitchell Smith and colleagues re-evaluated the E2997 trial with over six-years of follow-up data and found that patients who had been randomized to the FC arm were almost twice as likely to experience a myeloid neoplasia (e.g., acute myeloid leukemia or myelodysplastic syndrome). Genetic analyses of these cancers suggested that they were associated with cyclophosphamide exposure. Importantly, the overall risk of secondary cancer in either arm was small, and the difference was not statistically significant. Nonetheless, the results certainly highlight the uncertainty regarding optimal first-line regimens.

The US Intergroup Trial CALGB 10404 is a phase 3 trial comparing FCR to FR in patients with previously untreated CLL.  Update July 2013: the trial is no longer open to patient enrollment.

New Clinical Trial: Lenalidomide + Rituximab as Front-Line Therapy for Untreated Mantle Cell Lymphoma

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program is now enrolling patients in a new, investigator-initiated phase II study of lenalidomide in combination with rituximab in patients with previously untreated Mantle Cell Lymphoma (MCL). The study is led by Jia Ruan, MD. This study may be a good option for patients with MCL who need to travel to New York City to participate in a trial because lenalidomide, the study medication, can be taken at home. After the first month on study, patients will be seen in clinic on average of once a month.

Significant progress has been made in the treatment of mantle cell lymphoma; however, the majority of patients with Mantle Cell Lymphoma are not cured of their disease with current available chemotherapy-based options. The initial treatment for MCL is not standardized, and intensive chemotherapy does not seem to provide substantial benefit compared to conservative management in terms of long-term survival and quality-of-life measurements.

Researchers have recently discovered that the tumor microenvironment—the normal cells and blood vessels that surround a tumor–can contribute to tumor growth by providing blood supply and creating an environment that allows the tumor to grow. Biological compounds that disrupt the interaction and dependence of tumor cells with their microenvironment have shown promise in lymphoma therapy, including mantle cell lymphoma.

The purpose of this study is to test the synergy of combining lenalidomide, a biological agent that targets the tumor microenvironment, and rituximab, an antibody that targets lymphoma cells. By including a maintenance phase of lenalidomide and rituximab therapy, we hope to improve treatment effectiveness and maintain quality of life for patients. Continue reading “New Clinical Trial: Lenalidomide + Rituximab as Front-Line Therapy for Untreated Mantle Cell Lymphoma”

Lymphoma in the News: Lenalidomide Plus Rituximab Shows Promise as First-Line Therapy in Patients with Indolent Non-Hodgkin Lymphoma

By Peter Martin, MD

The results of a phase 2 study of lenalidomide plus rituximab in patients with previously untreated indolent lymphoma were presented at the American Society of Clinical Oncology annual meeting in June 2011. Investigators at MD Anderson Cancer Center treated 75 patients (41 with follicular lymphoma, 19 with marginal zone lymphoma, 15 with chronic lymphocytic leukemia) with the combination and found that 90% of patients responded, with 66% achieving a complete response. Treatment was generally well tolerated, with only 5 patients stopping due to toxicity.

These results are exciting due both to the promising response rate and the fact that cytotoxic chemotherapy was not a part of the treatment regimen: Lenalidomide is an immunomodulatory agent and rituximab is a biologic agent/monoclonal antibody.

Currently, the CALGB is conducting a similar phase 2 trial of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma. The trial is being led by Dr. Rebecca Elstrom at Weill Cornell Medical Center and will provide important confirmatory evidence in a larger group of patients treated at multiple centers around the country. (Update: this study is closed to enrollment.)

Dr. Jia Ruan at Weill Cornell is leading a study of lenalidomide plus rituximab as front-line therapy for patients with previously untreated mantle cell lymphoma (click here for more information on this trial).

A phase 3 trial comparing lenalidomide plus rituximab to chemotherapy plus rituximab in patients with previously untreated follicular lymphoma is being considered in Europe.