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Key news updates and reports from the latest meetings in oncology and hematology.

Sunday, May 31, 2015

ONLINE FIRST: John P. Leonard’s Top 5 Lymphoma Highlights at ASCO15


By Robert H. Carlson


CHICAGO--Fans who follow Twitter postings by John P. Leonard, MD (@JohnPLeonardMD), Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medical College, have come to enjoy his #LeonardList Top Abstracts tweets from important medical meetings.


He’s come through again with a “Top 5 Lymphoma Abstracts” list from this year’s American Society of Clinical Oncology Annual Meeting, tweeting one abstract a day in the five days leading up to the meeting.


In a telephone interview on Thursday, the evening before the start of the meeting, Leonard says he chose to highlight lymphoma research because it tends to be underrepresented at ASCO compared with the American Society of Hematology Annual Meeting--“But there are still some important abstracts at ASCO that patients and caregivers and those interested in the field should know about.”


The following is his list, along with some of his comments:


1.   Abstract 8555: “Exercise patterns and quality of life among survivors of aggressive lymphoma,” by Raina Mahajan Ferzoco, Mayo Clinic Department of Health Sciences Research, et al.

 “This focuses on patterns of aerobic exercise and quality of life in survivors of non-Hodgkin lymphoma-- it’s a correlation between exercise on their own and quality of life after treatment,” Leonard said. “We are learning more and more about the importance of exercise in cancer patients, and this study looked at more than 600 patients who had aggressive lymphoma and were survivors.

“The main take-home message is that significant exercise activity, as reflected by meeting recommendations from the standard guidelines, is associated with a better quality of life.

“It may be that there are a number of different benefits from counseling our patients on exercise. In the future it will be important to see if physicians intervene in this area and whether more patients will be exercising. Perhaps a prospective study will be done to see if interventions can actually cause improvements for patients in these outcomes.”


2.  Abstract 8505:” Title: Brentuximab vedotin plus AVD for non-bulky limited stage Hodgkin lymphoma: A phase II trial,” by Jeremy S. Abramson, Massachusetts General Hospital Cancer Center, et al.

“This study tested brentuximab vedotin plus AVD (doxorubicin, vinblastine, dacarbazine), substituting brentuximab vedotin for bleomycin in the standard ABVD regimen.

“This small study is in a more favorable population with non-bulky disease, yet there was a substantial 24-percent rate of grade 3 and 4 peripheral neuropathy. Similarly, several patients had febrile neutropenia, which is not that common with ABVD. So perhaps there is more toxicity than has been recognized with the brentuximab-containing version of the regimen.

“Also, the authors noticed several false-positive PET scans--more than we generally see with ABVD. This will be important for clinicians to pay attention to when they are using brentuximab in this combination, because we don’t want treatment decisions made on the basis of a false-positive PET scan. We really should not act on PET scans before confirming with a biopsy.

“An ongoing randomized trial will answer this in a more definitive fashion, but it does bring a bit of pause to the idea of routinely plugging in brentuximab until we have randomized data.


3. Abstract 8507: “Allogeneic or autologous transplantation as first-line therapy for younger patients with peripheral T-cell lymphoma: Results of the interim analysis of the AATT trial,” by Norbert Schmitz, Asklepios Hospital St. Georg, Hamburg, Germany, et al.

“This study focuses on fact that younger patients with peripheral T-cell lymphoma typically get an induction regimen--here it was CHOEP-14--and then in first remission usually get a stem cell transplant. There is some thought that allogeneic stem cell transplant might offer potential benefits over autologous transplant although with more toxicity than autologous transplant. These authors attempted to compare autologous transplant versus allogeneic transplant in first remission.

“The conclusion of this interim analysis is basically that this study is not going to be able to answer the question in a definitive way because a substantial number of patients relapsed before consolidation. So we still remain uncertain as to auto-versus-allo.

“One might interpret this as that allogeneic transplant is more toxic generally speaking so there is no reason to go on and use the more toxic regimen since autologous transplant, at least at this point, has not been effectively challenged by allogeneic.

“The other take-home message is that we need to work on getting more patients to transplant and having better induction regimens so these early relapses don’t occur.”


4.  Abstract 8515: “Phase I trial of 19-28z chimeric antigen receptor modified T cells (19-28z CAR-T) post-high dose therapy and autologous stem cell transplant for relapsed and refractory aggressive B-cell non-Hodgkin lymphoma,” by Craig Steven Sauter, Memorial Sloan Kettering Cancer Center, et al; and Abstract 8516: “Phase IIa trial of chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas,” by Stephen J. Schuster, Abramson Cancer Center, University of Pennsylvania, et al.

CAR-T cell therapy is getting a lot of attention and enthusiasm, and these studies look at two different approaches. The Memorial study took patients with poor-risk relapsed/refractory B-NHL and treated them with CAR-T cells following consolidative high-dose therapy and autologous stem cell transplant.

The Penn study similarly took relapsed B-cell lymphoma patients of various types, gave them similar therapy, and then gave them CAR-T cells.

“The net result is that some patients had fairly durable remissions, although the follow-up in these studies was generally in the range of one to two years at most--these are early days.

“This is promising data, but at the end of the day this is a relatively limited experience with aggressive lymphomas, in contrast to CLL and ALL. The challenge in interpreting these data is that the investigators are still working on optimal dosing and minimizing toxicity of cytokine-release syndrome. This is a heterogeneous group of patients, so it is difficult to interpret efficacy.

“And then there is patient selection. Patients getting on these studies often have to wait a couple of months so they have to have disease control in the meantime.

“So the jury is still out. I am encouraged that we are seeing progress in CAR-T therapy, but there is a lot of work to be done before we can say this is a standard of care or necessarily better than some of the other options we have.

“In other words: cautious optimism.” 


5.  Abstract 8504: “Evaluation of complete response rate at 30 months as a surrogate for progression-free survival in first-line follicular lymphoma studies: Results from the prospectively specified Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) analysis with individual patient data of 3,837 patients,” by Daniel J. Sargent, Mayo Clinic, et al.


“This is an analysis of more than 3,800 patients treated front-line for follicular lymphoma in different ways. The key question is whether there is an early endpoint that can predict progression-free survival, which is a standard endpoint commonly applied for follicular lymphoma studies.

“The challenge is that progression-free survival takes a long time to arrive at, and the authors wanted to know if there is a surrogate for progression-free survival that could then be used for drug approval or establishing superiority of one drug over another.

“They established that the percentage of patients who were in complete response at 30 months after therapy correlated with the ultimate progression free survival.

“I think this will lead to the complete response 30-month time point being an endpoint for various follicular lymphoma studies. The hope is that this will help speed up drug development.”




Top 10 Lymphoma Abstracts from #ASH14

Check out OT’s article about John Leonard’s Top 10 lymphoma abstracts from the most recent American Society of Hematology Annual Meeting in the 1/10/15 issue: