Burkitt lymphoma is a rare type of mature B cell lymphoma, characterized by the presence of the activating translocation of the myc oncogene and an elevated proliferative rate between 95 and 100 percent. It is also highly curable with modern therapy. There are three distinct clinical forms of Burkitt: endemic (African), sporadic (non-endemic), and immunodeficiency associated. All look the same under a microscope and have similar clinical behavior, but are different from the perspective of epidemiology, clinical presentation, and genetic features. For example, Epstein-Barr virus plays a role in both the endemic form and, to a lesser extent, the immunodeficiency form. Regrettably, none of the current therapies available take advantage of this fact.
Several successful therapies have been developed for Burkitt lymphoma (BL) but have never been compared in a randomized trial because of the rarity of the tumor. Fewer than 2,000 people each year are diagnosed with BL in the United States. These treatments typically include multiple chemotherapy drugs in combination and in sequence. Because BL often involves the central nervous system — either leptomeninges or parenchymal disease — these regimens also employ drugs that cross the blood-brain barrier in high dose, i.e., methotrexate and cytarabine, and/or drugs given by intrathecal injection. Two common BL regimens used in the US are CODOX-M/IVAC and HyperCVAD-methotrexate-high dose cytarabine.Back to top
The EPOCH-R Study
More recently, the National Institutes of Health (NIH) published an extremely successful pilot study of EPOCH-rituximab (R) in BL. This regimen can often be given entirely in the outpatient setting, making it easier than prior treatments. Memorial Sloan Kettering Cancer Center (MSK) is one of the lead accruing centers in a national trial, CTSU 9177, seeking to confirm these early results, with Dr. Ariela Noy leading the MSK effort.
Of note, HIV infection highly predisposes to the development of BL. HIV-infected patients are also eligible for this study under the auspices of the AIDS Malignancy Consortium (AMC), with Dr. Noy as the lead investigator for the AMC. An earlier AMC study led by Dr. Noy modified the CODOX-M/IVAC backbone to make the treatment more tolerable and efficacious. This treatment may be appropriate in certain cases of BL irrespective of HIV infection.Back to top
On the Horizon
Newer approaches in the treatment of Burkitt lymphoma are greatly needed. These approaches may make current therapies more efficacious or provide options in the case of relapsed or refractory disease. Recent work suggests that targeting the PI3-kinase pathway or cyclin-dependent kinase-6 may be of benefit. Several of our current trials target these pathways and are available to patients when first line therapy is unsuccessful.
Another potential approach involves supressing myc transcription via inhibitors of bromodomain and extraterminal family (BET) proteins, which bind acetylated proteins, including histones and regulate transcription. Preclinical data of myc-driven lymphoma suggests this is a very promising approach. MSK is currently participating in an ongoing BET inhibitor trial.
MSK is also participating in the Burkitt Lymphoma Genomic Sequencing Project that may elucidate potential targets for therapy. And we have a separate grant to look at genome sequencing pediatric and HIV-related BL.Back to top
Similar to Burkitt lymphoma, “double hit” lymphoma is a diffuse large B cell lymphoma with both a c-myc translocation and a bcl-2 translocation. These activating mutations drive proliferation and prevent apoptosis (programmed cell death), respectively. Other research suggests that the expression of both genes, as measured by immunohistochemistry, may be equally deleterious. It is ominous if the cancer cells are both rapidly dividing and not dying off. Thus, double hit lymphoma has been described as having a particularly bad prognosis with only about a 10 percent survival rate.
Because this is a rare tumor type, a consortium is necessary to study its treatment. The same CTSU 9177 study offering treatment with EPOCH-R in Burkitt lymphoma also accrued patients with diffuse large B cell lymphoma harboring a myc translocation. A subset of those patients had double hit lymphoma. Results were reported at the American Society of Hematology (ASH) Annual Meeting in 2014. Although the follow up time is short, more than 80 percent of patients enrolled in the study seem to have been cured using EPOCH-R. While the trial has met its accrual goals for double hit lymphomas and we are waiting for the data to mature, EPOCH-R remains a reasonable choice of therapy for this rare lymphoma. MSK physicians have been using EPOCH-R for decades and are experts in the nuances of the necessary cycle-to-cycle dose adjustments.Back to top
Patient Referrals and Clinical Trials
To refer a patient with Burkitt lymphoma, please call our lymphoma service referral line at 646-497-9137. To inquire about a clinical trial for a patient with Burkitt or double hit lymphoma, please contact Dr. Ariela Noy at 212-639-7423.Back to top