By Megan Martin, Communications Manager
A new Guideline detailing diagnosis, workup, and treatment options for Post-Transplant Lymphoproliferative Disorder (PTLD), as well as stronger recommendations for therapies in follicular lymphoma, topped the list of highlights in a presentation of the updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Non-Hodgkin’s Lymphomas (NHL). Andrew D. Zelenetz, MD, PhD, of Memorial Sloan-Kettering Cancer Center and chair of the NCCN Guidelines Panel for NHL, presented the updates at the NCCN 16th Annual Conference on March 11, 2011.
The most significant changes to the updated NCCN Guidelines™ for NHL are the addition of a new Guideline for Post-Transplant Lymphoproliferative Disorder (PTLD) and a second for NK/T-cell lymphoma. PTLD is a type of lymphoma that is a life-threatening complication and occurs after a solid organ or hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin, though T-cell lymphomas and Hodgkin lymphoma can also be present.
“PTLD has emerged as a significant complication of solid organ and allogeneic bone marrow transplantation and one the Panel felt was important to address in the updated Guidelines,” said Dr. Zelenetz. “Despite recent advances, it remains a major challenge to define indications for preemptive therapies for PTLD and to integrate novel therapeutic approaches with conventional therapies. The NCCN Guidelines now help to provide a solid framework to assist in diagnosis and treatment decisions.”
Dr. Zelenetz explained that understanding the pathogenesis of PTLD and utilizing early detection strategies, such as serial measurement of EBV-DNA load in peripheral blood samples, have assisted in the identification of high-risk patients.
Pertaining to diagnosis and workup of PTLD, the NCCN Guidelines provide recommendations for tests differentiated as either “essential” or “useful under certain circumstances” to help guide clinicians.
Depending on the PTLD subtype, treatment options in the NCCN Guidelines include the reduction of immunosuppression; if EBV-positive, using antiviral prophylaxis such as gancyclovir (Cytovene®, Roche); an anti-CD20 monoclonal antibody such as rituximab (Rituxan®, Genentech), or chemoimmunotherapy.
Significant updates were also made to the follicular lymphoma section of the NCCN Guidelines including a category 1 designation for two therapies previously given lower-level recommendations by the NCCN Guidelines Panel.
Bendamustine (Treanda®, Cephalon Oncology) plus rituximab is now a category 1 recommendation, from category 2A, as a suggested first-line treatment therapy for follicular lymphoma. Dr. Zelenetz detailed the results of a trial showing that bendamustine plus rituximab significantly improved progression-free survival and complete response rates when compared to standard therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab (CHOP-R) in patients with advanced follicular lymphoma, as well as mantle cell lymphomas.
In addition, post first-remission therapy options for follicular lymphoma including rituximab maintenance and chemotherapy followed by radioimmunotherapy are now category 1 recommendations, from category 2B. Recent studies support this category change showing that progression-free survival is dramatically improved with post-remission therapy (radioimmunotherapy after chemotherapy or rituximab maintenance); however, overall survival suggests that therapy at progression is effective.
“The development of these therapies suggests promise in the treatment of follicular lymphoma, which truly is a disease of paradoxes, as it is incurable despite a long natural history and highly responsive to therapy, but relapse is inevitable” said Dr. Zelenetz.
Dr. Zelenetz also touched upon the value of PET scans in both the assessment and response evaluation of follicular lymphoma.
FDG-PET is used widely for the staging of lymphoma, but few studies to date have evaluated FDG-PET in follicular lymphoma noted Dr. Zelenetz. However, outcomes from two recent trials suggest that FDG-PET imaging can distinguish between patients with indolent and aggressive lymphoma, and that the likelihood of aggressive disease increases in parallel with increases in standardized uptake value (SUV) measurements.
“The PET scan results can help guide the site for the optimal biopsy if there is concern about transformation of indolent lymphoma, however, it cannot replace a biopsy,” stressed Dr. Zelenetz.
In addition, recent analyses suggest that PET-CT scans may be useful in response assessment of follicular lymphoma.
“The predictive power of post-treatment PET is stronger than and independent of other prognostic factors,” said Dr. Zelenetz. PET-CT proved to be superior to conventional CT-based response assessment following first-line therapy for follicular lymphoma.
Lastly, Dr. Zelenetz spoke of recent research suggesting that the prognostic factor of the proliferative index (PI) as determined by quantitative image analysis (QIA) in mantle cell lymphoma is robust. Outcomes data notes that a PI of 30 percent is a clinically meaningful cut-off and identifies a group of favorable patients with a good outcome.
“This information can be particularly helpful in tailoring the intensity of therapy in future clinical trials,” said Dr. Zelenetz.
The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions. The most recent version of this and all the NCCN Guidelines are available free of charge at NCCN.org.