Category: Lymphoma News

FDA Approves Brentuximab for Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma

By Rebecca Elstrom, MD

The FDA granted accelerated approval last week to brentuximab vedotin for use in patients with Hodgkin lymphoma (HL) which has relapsed after 2 prior therapies, and patients with anaplastic large T cell lymphoma (ALCL) which has relapsed after one prior treatment. Weill Cornell Medical College participated in the studies that led to the approval.

Brentuximab vedotin is an antibody-drug conjugate (ADC); that is, a chemotherapy drug which has been attached to a monoclonal antibody in order to deliver the drug more specifically to target cells. In this case, the ADC targets CD30, a protein on the surface of the malignant HL cells and ALCL. Two phase 2 clinical studies were recently completed evaluating activity of brentuximab vedotin in HL patients who had had recurrence following autologous stem cell transplant and in ALCL patients that had relapsed after prior therapy. Response in both patient groups was striking. In HL, 73% of patients responded to treatment, with 32% achieving complete remission.  In ALCL, 86% of patients responded, with 57% achieving complete remission.

Major side effects of brentuximab vedotin in both groups of patients consisted of peripheral neuropathy, decreased blood counts, fatigue, nausea, rash and fever.

While long term results are still under investigation, initial response rates indicate that this drug represents an important new tool in the care of patients without other standard treatment options. Further studies are ongoing investigating how best to incorporate brentuximab vedotin into the routine care of patients with these lymphomas.

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.

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”