NCCN Guidelines Updates: Hematologic Malignancies

Andrew D. Zelenetz, MD, PhD

At the 18th Annual Conference of the National Comprehensive Cancer Network (NCCN), experts presented the latest updates to the NCCN Clinical Practice Guidelines in Oncology. The conference also featured two roundtable discussions that covered topics including cancer treatment costs, disparities in the quality and value of oncology care, the implications of big data in the field of oncology, and personalized cancer care. Here are highlights of the updates and perspectives from key opinion leaders.

Leukemia and Lymphoma

“There are exciting, emerging drugs that could well prove to be revolutionary treatments for chronic lymphocytic leukemia [CLL] and mantle cell lymphoma [MCL] in particular,” said Andrew D. Zelenetz, MD, PhD. “Ibrutinib is an oral agent that inhibits Bruton’s tyrosine kinase… In early studies, this agent has shown a broad range of activity in B-cell lymphoma; however, the responses in CLL, MCL, and Waldenström’s macroglobulinemia have been particularly dramatic. Two other agents demonstrating substantial activity in CLL and MCL are idelalisib, an inhibitor of the delta isoform of PI3K, and ABT 199, a small-molecule inhibitor of the pro-apoptotic Bcl protein. These small-molecule pathway inhibitors likely represent the future of treatment for these diseases.”

• For younger patients with MCL, including high-dose cytarabine (as in R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin] or in R-HiDAC [rituximab and high-dose cytarabine]) as part of the cytoreductive therapy prior to autologous stem cell transplantation was found to produce superior overall survival (OS) benefits as compared with induction with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alone. The finding was incorporated into the NCCN Guidelines as a recommendation for the frontline management of younger patients with MCL.
• For older patients with MCL, treatment with R-CHOP followed by maintenance therapy with rituximab was determined to improve OS.
• In managing CLL, there is a heightened focus on determining age-appropriate treatment by using a comorbidity score to better identify patients who are fit, and therefore eligible for chemotherapy. Patients have been broken down into the “young fit” group able to undergo treatment with the standard FCR (fludarabine, cyclophosphamide, rituximab); the “older with comorbidities” group for whom FCR is too toxic and gentler therapy such as rituximab and chlorambucil is preferred; and the “very frail patients” group of older patients whose lives are not limited by the disease.
• In patients with previously untreated follicular lymphoma, bendamustine plus rituximab is an acceptable alternative to R-CHOP. However, the previously reported improvement in progression-free survival (PFS) and in reducing toxic effects has been called into question by a more recent study presented at the American Society of Hematology in December 2012.
• Post-remission therapy with either radioactive antibodies or maintenance rituximab improved PFS in patients with follicular lymphoma; however, to date, there has been no impact on OS. Thus, these are listed in the NCCN Guidelines as potentially appropriate options after first-line therapy, but not required as part of standard of care.

Multiple Myeloma

“There are only a few changes in the treatment of multiple myeloma, but they’re very important ones,” said Kenneth C. Anderson, MD. “Within the last seven months, two novel agents to treat relapsed and refractory disease have received accelerated approvals from the FDA, based on the results of phase II clinical trials. These additions represent major new treatment options and improved outlook for patients; they promise to extend the progression-free survival and overall survival of patients who previously had no other therapies.”

• Carfilzomib (Kyprolis), a second-generation epoxyketone proteasome inhibitor that irreversibly blocks chymotryptic proteasome activity, was incorporated into the guidelines as salvage therapy. Carfilzomib was approved in July 2012 for the treatment of patients who have received at least 2 prior therapies, including treatment with bortezomib (Velcade) and an immunomodulatory therapy, and whose disease progressed on or within 60 days of the completion of the last therapy. Patient response to carfilzomib in clinical trials was durable and prolonged.
• Pomalidomide (Pomalyst), a second-generation immunomodulatory drug that augments host antitumor immunity, was added to the guidelines as salvage therapy. Pomalidomide was approved in February 2013 for treatment of patients who have received at least 2 prior therapies, including lenalidomide (Revlimid) and bortezomib (Velcade), and whose disease progressed within 60 days of the last treatment.
• In terms of treatment options for newly diagnosed myeloma, the combination of bortezomib with lenalidomide and dexamethasone is already included in the NCCN Guidelines. A new treatment regimen of carfilzomib in combination with lenalidomide and dexamethasone has now been added to the guidelines as a primary therapy for newly diagnosed patients. Due to the high frequency and extent of response demonstrated in newly diagnosed myeloma, this new regimen provides further evidence of the efficacy of combining a proteasome inhibitor with an immunomodulatory drug and dexamethasone as initial therapy.