COMMENTARY

ASH Wrap-up: Lymphoma and Leukemia -- The Take-Home Message

Bruce D. Cheson, MD; Jorge Cortes, MD; John P. Leonard, MD

Disclosures

December 15, 2010

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Introduction

Bruce D. Cheson, MD: Hello. I'm Bruce Cheson, Head of Hematology at Georgetown University Hospital and Directory of Hematology Research for the Lombardi Comprehensive Cancer Center in Washington, DC. It is my pleasure to welcome you to Medscape Oncology Insights Wrap-up of American Society of Hematology (ASH) 2010.

I am really pleased today to be joined by 2 of my colleagues and friends, Dr. Jorge Cortes, Professor and Deputy Chairman of the Leukemia Department at the MD Anderson Cancer Center, with the word "cancer" crossed off now—

Jorge Cortes, MD: That is correct.

Dr. Cheson: --in Houston, Texas; and Dr. John Leonard, Professor of Medicine at the Cornell Weill Medical College in New York, NY. Thank you for joining me today.

Leukemia: Kitchen Sink vs Substitution Approach

The ASH meetings really had some interesting presentations, some showing exciting new drugs and some showing that maybe the old stuff is as good as the new stuff. John, what should your take-home message be for the viewers about lymphoma?

John P. Leonard, MD: I would say that many of the standard-of-care approaches that we were using, at least before ASH -- whether for Hodgkin lymphoma, large cell lymphoma, or follicular lymphoma -- really have not changed here at the ASH meeting. I think that we have seen some follow-up of some of the recent practice-changing studies. We should continue to do what we have been doing; particularly in follicular lymphoma and for initial therapy for Hodgkin lymphoma as well. To some degree, it is a little less exciting that we aren't seeing new, definitely better upfront therapies.

On the other hand, I think we are continuing to see data on new drugs and new approaches that people in practice need to keep an eye on, enroll in the clinical trials, keep in mind for patients with resistant disease, and hopefully we'll be continuing the process of moving into front-line therapy in the near future.

Dr. Cheson: Returning to your point about initial therapy and having no changes in our approach. We could be debating that for a while based not on data from this ASH meeting, but on data from the last ASH meeting on bendamustine/rituximab -CHOP. Do you think that is going to be changing the initial therapy of follicular lymphoma?

Dr. Leonard: I think there are 2 paradigms for the initial therapy of indolent lymphoma. One of those is the "kitchen sink approach." The idea of "let us combine every drug we can think of." It could be chemotherapy plus rituximab, plus maintenance rituximab, plus whatever else we can think of with the goal that by throwing everything at the patient upfront, we could potentially cure the patient or make the patient live longer. The addition of maintenance rituximab, which we have seen an update on here at this meeting, is part of that approach.

Bendamustine now being incorporated in upfront therapy and showing a progression-free survival, one could argue, compared with CHOP-rituximab is also part of that chemotherapy-based approach.

The other paradigm in follicular lymphoma is the substitution approach. Can we substitute for chemotherapy? Let us use less toxic treatment. The idea may not be that this is better, although we would like it to be better. But can we substitute and get rid of chemotherapy or at least delay it with a more tolerable treatment? We are really going in 2 directions. Patients have preferences, and doctors have preferences, so it is going to be challenging to sort out which therapy is better in the long term with respect to the gold standard of overall survival.

It is nice that we have these options for patients, but I am not sure that it is going to be easy to sort out which in the long term is better given all of these considerations.

Dr. Cheson: What are the challenges with all of these new drugs in the relapse setting?

Dr. Leonard: In the relapse setting the issue is that we have lots of drugs that have 25% response rates, or 20% response rates, in heterogeneous groups of patients. The question is, can they complement our existing therapies, can they overcome drug resistance, and are they worth pursuing in the long-term multicenter studies that are really going to be needed to define their approval? One of the paradigms has been "let's combine a new drug with rituximab." We have seen 2 examples of this at this meeting. Galiximab and bortezomib both showed good single-agent and combination phase 2 activity, but the randomized data for these 2 agents were not compelling. We are left with a tradeoff that is going to encourage some investigators to shy away from that approach in the relapse setting and maybe pursue it a little more in the upfront setting.

Bendamustine is now becoming the standard drug of choice against which to compare new drugs in the relapse setting.. We are trying to look at drugs for the very bendamustine-refractory or -relapse patient. We are going to see more and more studies focusing on that area that perhaps can give us more definitive answers.

Lymphoma: New Drugs, New Targets

Dr. Cheson: Jorge, what is your take home message for the viewers from the leukemia world?

Dr. Cortes: In some ways it is not much different than what John described for the lymphomas. We have an outlier, which is chronic myelogenous leukemia, for which we have been able to get all these new drugs. It looks like every year we come up with yet another very good drug, or we are moving drugs upfront and getting better results. So that has been great.

But on the other hand, out of all of the leukemias, certainly the acute leukemias are where the progress has been a lot slower. I started my training treating frontline acute myelogenous leukemia with anthracycline and araC and I don't think that has changed much. We have gone through a number of targets and a number of this and a number of that. I think there is a lot of excitement here, both in the discovery arm of finding potential new targets and in the translation into finding potential new agents for those targets.

What has been a real challenge is that we have not yet been able to learn how to incorporate these. Traditionally we just said, "Okay, well, we have the chemotherapy, so let us just add these and see what happens." We have not been very successful with that approach.

There is excitement at this meeting because new drugs are showing promise and suggest early potential. There are even some potential new targets that are also very exciting. We need to work a lot harder to make that link and connect that to improvements in the outcomes of patients, certainly in the acute leukemias where we still have a lot to gain.

One example where that has helped is in the Philadelphia-positive acute lymphoblastic leukemia, where the addition of the tyrosine kinase inhibitors to standard chemotherapy does seem to add to our results in a good way. However, in many others, certainly acute myelogenous leukemia, there is still a lot of progress to be made. There is a lot of hope from what we are seeing, but there is a lot of work in understanding all of this.

Correlative Science and Clinical Trials

Dr. Cheson: There are 2 themes that I got from your presentations. Number one, it is critically important to continue to do correlative science studies with our clinical trials. I know that in the CLGB, no study gets activated without some correlative science, and I am sure that is the same at the MD Anderson Cancer Center (without the "cancer").

The second point is -- and I'm sure none of us can stress this too strongly -- the importance of clinical trials. We cannot be complacent. ABVD [adriamycin, bleomycin, vinblastine, and dacarbazine] is the standard, CHOP [Cytoxan (cyclophosphamide), hydroxydaunorubicin, Oncovin (vincristine), prednisone] is the standard, or 7+3 is the standard. We have these new drugs and the only way we are going to find out whether they work is to get patients on clinical trials. The number of patients on clinical trials has been sorely disappointing. I think it is a little better in studies of heme malignancies vs solid tumors, but it has been very disappointing. The more quickly we get the trials completed, the more quickly we know whether to continue that therapy or flush it.

I think the two of you have a long-standing career of putting patients on clinical trials and making important observations as a result, and I think what our audience needs to take home is that we have not made progress in front-line leukemia -- maybe in front-line large cell. We can argue about follicular, but certainly not in mantle cell front-line leukemia. But the only way we are going to make progress is to study those new drugs as quickly as we can, rationally put them together, and then come up with a new regimen focusing on targets rather than focusing on the old standards because it was "good enough for Grandpa."

Closing Remarks

So, with that, I would like to thank our guests, Dr. Cortes and Dr. Leonard, and I would like to thank our audience. This has been Medscape Oncology ASH 2010, the wrap-up on leukemia and lymphoma. I hope everybody enjoyed this presentation and learned something from it. We look forward to seeing you again in the future.

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