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Real-world CNS outcomes in Burkitt lymphoma
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Figure 4. Cumulative incidence of central nervous system recurrence according to first-line chemotherapy regimen. (A-D) The cumulative incidence of central nervous system (CNS) recurrence in: (A) all patients (n=570) treated with CODOX-M/IVAC, hyper-CVAD/MA, or DA-EPOCH-R; (B) patients with stage 4 disease (n=413); (C) patients without CNS involvement at diagnosis; and (D) patients with CNS involvement at diagnosis. Subhazard ratios were derived from univariate competing-risk models com- paring hyperCVAD versus CODOX-M/IVAC, or DA-EPOCH-R versus both high-intensity regimens combined. 95% CI: 95% confidence interval; SHR: subjazard ratios.
The prevalence of baseline CNS involvement in this
real-world BL cohort (19%) is higher than that in phase II
trials (10-14%)8,9,11-13,21-24 or in a recent retrospective study of
264 patients treated with immunochemotherapy (8%),5
but lower than that in a phase III trial (25%).10 These dif-
ferences may reflect both selection bias in smaller trials,
and less rigorous CNS staging in routine practice (com-
pared with the phase III setting), in which the use of CSF
cytology or flow cytometry is not standardized. Our
study had sufficient power to demonstrate independent
impacts of CNS involvement on rates of complete
response, PFS, and OS in BL, as suggested by some tri- als,8,13,22,25 but not by others.9,10,21,24,26
Interestingly, the choice of using an immunochemother- apy regimen did not differ according to CNS involvement, and CNS involvement was prognostically unfavorable regardless of the use of first-line rituximab or any specific regimen, including those that contained HDMTX. Collecting granular data on CNS-directed intrathecal ther- apy proved challenging in this retrospective study, but intensive administration schedules designed for patients
with CNS involvement appeared difficult to execute in real-world practice. All regimens used in our cohort (hyperCVAD/MA, CODOX-M/IVAC, and DA-EPOCH- R) involve intensified intrathecal regimens for patients with CNS disease, which requires thorough staging to identify subclinical CNS invasion and expertise in the delivery of intrathecal agents, including the use of intra- ventricular devices. We could not determine whether these schedules were correctly applied in most patients, and whether barriers to effective CNS-directed therapy were related to physicians’ preference, patients’ refusal, or system-level factors. Furthermore, we did not have data on the use of intraventricular reservoirs, although their availability may affect the efficacy of intrathecal therapy. Both poor prognosis with CNS involvement and subopti- mal delivery of CNS-directed therapy indicate that patients with CNS disease need more efficacious and practicable treatment approaches that can be consistently administered in routine clinical practice.
CNS recurrence after standard immunochemotherapy regimens was uncommon (6%) and exclusive to patients
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