Blood cancers

EHA 2022: Low intensity regimen preferred as first line therapy in Burkitt lymphoma

Dr Martine Chamuleau

An investigation into the optimal first line chemotherapy treatment for high-risk Burkitt lymphoma (BL) has shown that a low intensity DA-EPOCH-R regimen appears to be preferable given its lower risk of toxicity.

Results from the first prospective randomised trial comparing two different chemotherapy regimens in BL were presented at EHA 2022, showing that a DA-EPOCH-R regimen resulted in comparable Complete Metabolic Remission (CMR) and survival rates as high intensity (R-CODOX-M/R-IVAC) regimens, but was associated with significant less infectious complications, transfusions and hospitalisation days.

Led by Dr Martine Chamuleau of Amsterdam University Medical Center, the multicentre trial enrolled 89 patients with newly diagnosed, high-risk BL were eligible. High-risk was defined as any of: elevated LDH, WHO PS ≥ 2, stage III/IV, mass ≥ 10 cm. Patients with CNS involvement were excluded.

Patients in Arm A were assigned to treatment with  cyclophosphamide, doxorubicin, vincristine, rituximab, and methotrexate (R-CODOX-M) or etoposide, ifosfamide, cytarabine, and rituximab (R-IVAC).

Patients in Arm B received treatment with rituximab, etoposide, doxorubicin, vincristine, prednisolone, and cyclophosphamide (DA-EPOCH-R).

After a median follow up of 19 months and up to 60 months, the progression free survival (PFS) and overall survival outcomes (75% in arm A and 76% in Arm B) were similar in both arms, with no significant differences.

In arm A 28/43 (65%) patients achieved CMR and in arm B, 27/41 (66%) of patients treated with DA-EPOCH-R achieved CMR.

However toxicity and complications appeared to be greater for patients treated with R-CODOX-M or R-IVAC regimens.

In arm A 79% of patients experienced grade 3-5 adverse events and 30 serious adverse events SAE were reported in 21 patients. In Arm B, 73% patients had grade 3-5 adverse events and 28 serious adverse events were reported in 20 patients.

The most common serious adverse events were infections and febrile neutropenia, which occurred in 73% of patients in arm A and 46% of patients in arm B (p=0.04).

In arm A patients received a median of two platelet transfusions and five red blood cell transfusions vs 0 and one, respectively in arm B (p<0.01 for both). In arm A patients were hospitalised for a mean of 46 nights compared to 25 nights for patients in arm B (p<0.01).

So based on these results, DA-EPOCH-R seems to be the preferred regimen appears to be preferable for high risk Burkitt lymphoma patients without CNS localisation, concluded Dr Chamuleau.

She added that data on CNS relapses was still being evaluated but until now there appeared to be none in the DA-EPOCH-R arm.

Speaking in a follow up question-and answer forum Professor John Seymour of the Peter Mac Cancer Centre Melbourne noted that the trial had been designed as a superiority study and had been terminated prematurely after recruiting only 89 of a planned 260 patients. He questioned whether the trial had power to show clinically significant differences in two year PFS.

Dr Chamuleau responded that the study had originally been planned to have 80% power to show a difference and the lower number of patients meant it had 34% power, which she still believed had clinical relevance.

She said the trial had been planned as the first direct comparison of chemotherapy regimens in BL, with the aim of confirming previous trial results showing 70% 2-year PFS with R-CODOX-M or R-IVAC regimens and a higher 85% 2-year PFS with DA-EPOCH-R.

Dr Chamuleau said the low intensity regimen was preferred for its  lower toxicity. The original justification for the low-intensity continuous DA-EPOCH-R regimen was based on the pharmacodynamic principle of longer exposure to rapidly proliferating tumour cells in BL. Variations in drug clearance were the justification for a dose adjusted regimen, she added.

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