Author: lymphomaprogram

Located on the Upper East Side of New York City, the Lymphoma Program at Weill Cornell Medical College/NewYork Presbyterian Hospital is internationally recognized for our efforts to enable patients with non-Hodgkin lymphoma, Hodgkin disease and related disorders to have the best possible clinical outcome, including cure when possible.

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 Since then, FC has been replaced by FCR (FC plus rituximab) on the basis of even better response rates demonstrated in subsequent trials.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: Choice of Pre-Transplant Chemotherapy Regimen May Not Be As Important As Other Factors in Mantle Cell Lymphoma

By Peter Martin, MD

Investigators at Fred Hutchinson Cancer Research Center in Seattle recently reported the results of retrospective study of 118 patients with mantle cell lymphoma. After receiving a variety of first-line chemotherapy regimens, including R-HyperCVAD and R-CHOP, 85 patients underwent consolidation with autologous stem cell transplantation. Initially, it appeared that patients who received an aggressive induction regimen, like R-HyperCVAD, had a better outcome following stem cell transplantation. Interestingly, after controlling for other prognostic factors, like age, LDH, White Blood Cell count, and performance status, it became apparent that choice of induction chemotherapy had little effect on outcome after transplant. In other words, patients that had a better baseline prognosis were more likely to be treated with aggressive first-line regimens, which gave the appearance that the more aggressive regimens were responsible for better outcomes. Click here to read the abstract.

This study is important because it helps us to contextualize the results of many of the phase 2 studies that have been published on mantle cell lymphoma. It is possible that the results of phase 2 studies appear to be more or less impressive than standard therapies because there is no comparison group; i.e., it is the baseline prognostic factors of the patients that explain the results rather than the treatment regimen being tested. Retrospective studies, such as the study from Seattle, are also prone to bias because it is difficult to control for everything, particularly prognostic factors that we don’t yet know about. That is why randomized studies comparing at least two regimens are of critical importance. Only randomized studies can distinguish the between the good and bad effects of two or more regimens. Continue reading “Lymphoma in the News: Choice of Pre-Transplant Chemotherapy Regimen May Not Be As Important As Other Factors in Mantle Cell Lymphoma”