Dose-Adjusted Chemo Regimen Shows Efficacy in Burkitt Lymphoma, Regardless of Age or HIV Status

Investigators may have identified an alternative treatment to dose intense chemotherapy through dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for adults with untreated Burkitt lymphoma and diffuse large B-cell lymphoma, according to findings of an ongoing, multicenter, phase 2 study (NCT01092182).¹

At a median follow-up of 58.7 months, the 4-year event-free survival (EFS) rate with the regimen was 84.5% and the 4-year overall survival (OS) rate was 87.0%. While the 4-year EFS rate was 100% in low-risk patients, the rate in high-risk patients was 82.1%. Investigators found that DA-EPOCH-R was equally effective regardless of HIV status across all age groups and International Prognostic Index risk groups.²

Preliminary data showed that the regimen was found to be less toxic than standard dose-intensive chemotherapy and highly effective, although it still highlights a need for improved therapies for adult patients with cerebrospinal fluid (CSF) involvement.

“We knew that Burkitt lymphoma is curable with dose-intensive chemotherapy, but that treatment can be acutely toxic for adult patients,” lead study author Mark Roschewski, MD, senior clinician and clinical director of the Lymphoid Malignancies Branch at the National Cancer Institute, stated in a press release. “With this finding, we not only have a potentially curative treatment option for these patients that’s less toxic, but one that appears effective for most adults, including elderly patients and those with HIV and other comorbidities who might not be able to receive standard treatment.”

A total of 113 patients were enrolled in the study across 22 centers, 98 of whom (87%) were deemed high-risk. Bone marrow and/or CSF were involved in 26% of patients (n = 29), while 25% of the patient population (n = 28) were HIV positive.

In the trial, which launched on March 24, 2010 and ran until 2017, patients were categorized as having low- or high-risk disease, with low-risk defined by stage I or II disease and high-risk as stage III or higher. The median age was 49 years (range, 18-86), with 62% of patients being 40 years of age or older. Patients received an intravenous infusion of DA-EPOCH-R in 21-day treatment cycles. The primary endpoint was EFS, with toxicity and predictors of EFS and OS marking the secondary endpoints.³

All patients were given DA-EPOCH-R, with all patients starting at dose-level 1; the following cycles contained adjusted doses of etoposide, doxorubicin, and cyclophosphamide. Patients who were deemed low-risk were given rituximab (Rituxan) for 2 cycles. Following a negative PET scan, patients would continue with an additional 4 cycles of DA-EPOCH-R without though CNS prophylaxis, though in the event of a positive result, CNS prophylaxis was given with the following 4 cycles. For high-risk patients, a PET scan followed the first 2 cycles of DA-EPOCH-R. Provided disease progression was not observed, they were able to continue on with the next 4 cycles of therapy. If this patient group continued without any CNS involvement, they were given 8 doses of phylactic intrathecal methotrexate.

Regarding safety, 5 treatment-related deaths (4%) occurred during the study, the majority of which were from sepsis or multiorgan failure. Investigators also found that patients in the study who experienced metastasis to the central nervous system, specifically those who had involved CSF, had the highest risk of treatment-related death or treatment failure. Febrile neutropenia was another AE identified and occurred in 16% of cycles (n = 89), while tumor lysis syndrome was rare (5%). Of the 7 patients with ECOG 3 or 4, 5 are currently alive and without disease.

For the rarer cases of adults with Burkitt lymphoma, treatment-related toxicities remain a significant obstacle to treatment. The DA-EPOCH-R regimen was shown to be effective in the pilot study and seems to be an efficacious alternative to chemotherapy. Based on the results of this study, investigators conclude that future studies are needed to determine how best to treat adult patients with Burkitt lymphoma and DLBCL who have involved CSF.

References

1. Study confirms effective, less toxic alternative to standard treatment for adults with Burkitt lymphoma. News release. American Association for the Advancement of Science. Published May 26, 2020. https://bit.ly/2X6R2Wb
2. Phase II study of dose-adjusted EPOCH-rituximab in adults with untreated Burkitt lymphoma and c-MYC diffuse large B-cell lymphoma. ClinicalTrials.gov. Updated May 18, 2020. Accessed June 2, 2020. https://clinicaltrials.gov/ct2/show/NCT01092182
3. Roschewski M, Dunleavy K, Abramson JS, et al. Multicenter study of risk-adapted therapy with dose-adjusted EPOCH-R in adults with untreated Burkitt lymphoma. J Clin Oncol. 2020;38(suppl; abstr 2519).doi:10.1200/JCO.20.00303