Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for patients with hematologic malignancies. There are 2 primary types of HSCT: autologous, where the cells are taken from the patient, and allogeneic, where the cells come from a matched sibling donor or an unrelated donor. Advances in HSCT include the introduction of reduced-intensity conditioning regimens that allow HSCT in older patients and alternative graft sources that afford a donor for nearly all patients who require a transplant. In this Q&A session, Sergio Giralt, MD, Chief of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, shares insights into emerging data that can rationally inform clinical decision making in the management of patients undergoing HSCT for hematologic malignancies.
How do you decide whether patients are eligible to receive a double cord transplant?
Sergio Giralt, MD: We currently have an algorithm that we try to follow. If the patient is younger than 55, we have a good cord, and they have less than 10% blasts, we think this is a good candidate for a double cord because our data suggests a double cord is associated with a lower risk of relapse.
If we don't have a good cord and the patient has no better donor than a mismatch, we will do post-transplant cyclophosphamide. If the patient has a druggable target, such as an IPH mutation or FLT-3, we will encourage them to go on posttransplant maintenance with the appropriate drug. If the patient does not have a druggable target and there are no contraindications, we will do a hypomethylating agent posttransplant.
What's the data for hypomethylating agents posttransplant?
Dr. Giralt: Marcos and I did the phase 1 trial many years ago at MD Anderson, which showed it's safe. We only gave 4 cycles. We compared it to a historical group, and it looked better. There's a randomized trial that's going on at MD Anderson that has not been read out. Celgene just finished a phase 1 trial with oral azacitidine in patients with high risk for relapse who have less than 5% blasts. That study is being published and a phase 3 is being planned for oral azacitidine. Biologically, it makes sense. Hypomethylating agents increase the expression of class one and class two antigens and leukemic blasts so that they may get more recognizable.
What other drugs can we try?
Dr. Giralt: This is a big discussion that we have. My practice has been that if my perception that your risk of relapse is over 30%, I'm going to do something. If it's a myeloid leukemia, I'll do azacitidine. If it's a lymphoid leukemia, we have an ixazomib protocol. Ixazomib is the oral bortezomib. You may get a two-fer because proteasome inhibition may reduce your risk of graft-versus-host disease (GVHD), so it allows you to taper immune suppression without getting flares of GVHD. Ixazomib is active in lymphoid malignancy, so you may also get a reduction in relapse.
If there is an antigen that we can target with monoclonal antibodies, we will give either brentuximab or rituximab. We don't have experience using inotuzumab or gemtuzumab ozogamicin posttransplant yet. We're trying to get that.
Finally, the drug which I'm very interested in is lenalidomide. Lenalidomide at a low dose is a very important immunomodulatory drug. It reduces the risk of relapse after allogeneic transplant for myeloma. The message that it increases your risk of GVHD after allogeneic transplant is true at a high dose. It may not be true at 5 milligrams every other day.
I have anecdotes for everything, but the reality is we should try to put patients on protocol. If we don't have a protocol for patients, I have not been putting my hands in my pocket. I can tell you we have a clinic of people getting azacitidine now. So, one of the first patients we put on azacitidine for relapse prevention is still on azacitidine now, almost 12 years later. And she doesn't want to come off. Her first remission, after transplant, lasted 7 months, and now she's been in remission almost 12 years after her second transplant. An anecdote, but it speaks a lot.
About Dr. Giralt
Sergio A. Giralt, MD is Chief of the Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center. His clinical activity and research focus on stem cell transplantation for patients with blood disorders and he is internationally recognized as a bone marrow transplantation expert. He trained and worked for many years at the University of Texas MD Anderson Cancer Center, where he was Deputy Chair of the Department of Stem Cell Transplantation and Cellular Therapies.
Dr. Giralt currently serves as vice president of The American Society for Blood and Marrow Transplantation, is a member of The Bone Marrow Foundation's Medical Advisory Board as well as an ASH representative for the FDA-Cell Therapy Liaison Meeting Working Group. Additionally, Dr. Giralt has authored more than 250 scientific papers, which have appeared in journals such as Blood, Bone Marrow Transplant, Leukemia, and Biology of Blood and Marrow Transplant.
This Q&A was recorded during the live meeting, Optimizing the Treatment of Hematologic Malignancies With HSCT. Transcript edited for clarity.
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Any views expressed above are the speaker's own and do not necessarily reflect the views of i3 Health.