By Peter Martin, MD
Brentuximab vedotin (BV), is an antibody drug conjugate that selectively binds to a protein called CD30 on the surface of cells (e.g., Hodgkin lymphoma cells) and delivers a payload of toxin (monomethyl auristatin E) directly to that cell; i.e., a Trojan horse approach to cancer therapy. In 2011, the United States Food and Drug Administration (FDA) approved BV based on a phase II trial in which BV demonstrated an overall response rate (ORR) of 75% and complete response rate (CR) of 34% in patients with Hodgkin lymphoma that had relapsed following autologous hematopoietic cell transplantation (AHCT). Given the promising data, investigators at City of Hope and Weill Cornell Medical College-New York collaborated to evaluate the use of BV prior to AHCT. The standard approach for patients that relapse after first-line therapy includes cytotoxic chemotherapy followed by AHCT. However, this approach can be challenging for some patients and may be associated with some short-term and long-term toxicity. Use of BV prior to AHCT may cause patients some side effects and improve their quality of life prior to AHCT. Preliminary data from this trial were presented yesterday at the 56th Annual Meeting of the American Society of Hematology (ASH).
All patients had biopsy proven Hodgkin lymphoma that had relapsed following therapy with ABVD, BEACOPP, or a combination +/- radiation. Patients were treated with a standard dose of BV intravenously every 3 weeks for a maximum of 4 cycles. Over two-thirds of patients responded, including one third of patients that obtained a CR) and roughly half of the patients were able to proceed to AHCT without receiving additional chemotherapy. Treatments were well tolerated by all patients and no transfusions were required or neutropenic fevers developed.
The results from this trial suggest that BV may be an efficacious option as a first line salvage therapy. It is well tolerated and does not hinder stem cell collection or engraftment. Additional studies will be required to confirm these results. Moreover, this study may lay the groundwork for future studies with promising combinations.
Update: this study is closed to enrollment.
The Weill Cornell Hematologic Malignancies & Bone Marrow Transplant Program is now enrolling men and women with relapsed or refractory lymphoma (non-Hodgkin or Hodgkin) and who are in need of a stem cell transplant for an investigator-initiated clinical trial. The principal investigator is Tsiporah B. Shore, M.D. For more information about the study, please call June Greenberg, RN at (212) 746-2651, e-mail June at firstname.lastname@example.org, or call the Bone Marrow Transplant Program at (212) 746-2119.
This clinical trial is for men and women whose lymphoma (non-Hodgkin or Hodgkin) did not respond to treatment or has returned after responding to previous therapy, and who are in need of a stem cell transplant.
The purpose of the study is to test the safety and effectiveness of giving the drug Bendamustine, followed by high dose chemotherapy, within two weeks prior to a stem cell transplant for lymphoma that has not achieved a complete response to salvage chemotherapy (treatment used for relapsed disease).
Bendamustine is FDA-approved for the treatment of Chronic Lymphocytic Leukemia. Although Bendamustine has been used in stem cell research studies, the timing and combination of Bendamustine and the conditioning regimen BEAM (carmustine, etoposide, cytarabine arabinoside, and melphalan) prior to transplant is not approved by the FDA, thus the combination therapy used in this research study is considered experimental.
Autologous stem cell transplants refer to stem cells that are collected from an individual and given back to that same individual after high dose chemotherapy. With this type of transplant, the person’s stem cells are obtained prior to high-dose chemotherapy, frozen, stored-if necessary, and then given back afterward. Allogeneic stem cell transplantation refers to stem cells that are collected from a donor.
Study participants will receive Continue reading “Investigator-Initiated Trial: Sequential Regimen of Intensive Chemotherapy Followed by Stem Cell Transplant for Refractory 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”