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. 2022 Jan 25;6(2):460-472.
doi: 10.1182/bloodadvances.2021005999.

Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

Megan Fleming  1 , Ying Huang  2 , Emily Dotson  1 , David A Bond  2 , John Reneau  2 , Narendranath Epperla  2 , Lapo Alinari  2 , Jonathan Brammer  2 , Beth A Christian  2 , Robert A Baiocchi  2 , Kami Maddocks  2 , Yazeed Sawalha  2
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Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

Megan Fleming et al. Blood Adv. .

Abstract

The optimal timing for administering high-dose methotrexate (HDMTX) when combined with (R)CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, with/without rituximab) is unclear. Recent data showed that the administration of prophylactic HDMTX before day 10 of R- CHOP may lead to fewer treatment delays. Herein, we report our experience with HDMTX administered on day 1 of (R)CHOP in patients with aggressive non-Hodgkin lymphoma (NHL). We identified 140 patients treated with ≥1 cycle of HDMTX combined with (R)CHOP for prophylaxis against (n = 84) or treatment of (n = 56) central nervous system (CNS) involvement. Overall, (R)CHOP treatment delays ≥7 days (4% of cycles, 13% of patients), doxorubicin, and/or cyclophosphamide dose reductions (1% of cycles, 6% of patients) or (R)CHOP discontinuations due to toxicity (4% of patients) were uncommon. Neutropenic fever (NF) occurred in 7% of cycles and 24% of patients and was more common during HDMTX-containing cycles. Acute kidney injury (AKI) occurred in 19% of cycles but was mostly grade ≤2. Grade ≥3 hepatotoxicity and mucositis were uncommon (each 2% of cycles). In the prophylaxis cohort, the rates of NF and grade ≥2 AKI were lower in patients who initiated HDMTX with cycle 2 or later (11% vs 30%, P = .03 and 16% vs 39%, P = .03, respectively). Our data show that HDMTX administration on day 1 of (R)CHOP may improve the deliverability of (R)CHOP and the overall safety of the regimen compared with historical data of HDMTX administration on day 10 or later of R-CHOP. Delaying prophylactic HDMTX beyond cycle 1 of (R)CHOP may reduce the risk of NF and AKI.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram for patient selection.
Figure 2.
Figure 2.
Cumulative incidence of relapse, PFS, and OS in patients with DLBCL and HGBCL receiving prophylactic HDMTX.
Figure 3.
Figure 3.
Cumulative incidence of CNS relapse/progression, PFS, and OS in patients with DLBCL and HGBCL with known CNS involvement.
See this image and copyright information in PMC

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