Abstract
Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT: 5.7% vs 5.8%, P =.98; 3-year difference: 0.04% (−2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n = 1253). In patients with a high CNS international prognostic index (n = 600), the 3-year CNS relapse rate was 9.1%, with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk vs i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.
| Original language | English |
|---|---|
| Pages (from-to) | 2499-2511 |
| Number of pages | 13 |
| Journal | Blood |
| Volume | 139 |
| Issue number | 16 |
| Early online date | 7 Jan 2022 |
| DOIs | |
| Publication status | Published - 21 Apr 2022 |
Bibliographical note
Funding Information:The authors thank the following health care professionals for their expert dedication to data collection: Catherine Thieblemont (H?pital Saint-Louis, Assistance Publique-H?pitaux de Paris), Sridhar Chaganti (University Hospitals Birmingham), George Follows (Cambridge University Hospitals NHS Foundation Trust), Anca Prica (Princess Margaret Cancer Centre), Adam Olszewski (Brown University and Lifespan Cancer Institute), Barbara Botto (AOU Citt? della Salute e della Scienza di Torino), Corinne Haioun (Hospital Henri Mondor), Caroline Besson (Centre Hospitalier de Versailles), Olivier Tournilhac (Service d'H?matologie et de Th?rapie Cellulaire, CHU Estaing, Universit? Clermont Auvergne), Pietro Di Ciaccio (St Vincent's Hospital Sydney), Agnes Olivrie and Julie Abraham (H?matologie Clinique et Th?rapie Cellulaire, CHU de Limoges), Dipti Talaulikar and Caitlin Coombes (Australian National University and Canberra Health Services), Raul Cordoba (Fundacion Jimenez Diaz University Hospital, Health Research Institute), Adolgo de la Fuente (MD Anderson, Madrid, Spain), Rebecca Oliver and Laura Percy (University Hospitals Bristol NHS Foundation Trust), Kamel Laribi and Catherine Truong (Centre Hospitalier Le Mans, Le Mans), Ruth Clifford (University Hospital Limerick), Jordan Carter and Andrew Evens (Rutgers Cancer Institute), Brian Henessy (University Hospital Waterford), Wendy Osborne and Thomas Creasey (Newcastle Hospitals NHS Foundation Trust), and Javier Penalver and Maria Garcia Roa (Hospital Universitario Fundacion Alcorcon).
Conflict-of-interest disclosure: M.R.W. received conference fees from Takeda, Janssen, and Kite/Gilead; honoraria from Abbvie and Kite/Gilead. T.A.E. received honoraria from Roche, Kite/Gilead, Janssen, Abbvie, AstraZeneca, Loxo Oncology, Beigene, and Secura Bio; provided consultancy for Roche, Abbvie, Loxo Oncology, Incyte, Secura Bio. M.A. received honoraria from Takeda and Roche; research funding from Pfizer. E.S. received honoraria from Riemser Pharma GmbH; research funding from Roche and Abbvie. M.K. provided consultancy to Roche, Antegene, and Genor Biopharma. M.N. received research funding from TG Therapeutics, Genmab, Genentech/Roche, and Gilead. K.L.L. received honoraria from AstraZeneca, Janssen, and Roche; patents and royalties from Janssen and Novartis; provided consultancy to AstraZeneca. A.K.Ø. received travel expenses from Abbvie. A.S. received honoraria from Janssen. N.S. received honoraria and membership on an entity's board of directors or advisory committees for Abbvie, Janssen, and Roche. L. Roulin received travel expenses from Janssen. K.M. received travel and meeting expenses from Bristol-Myers Squibb. N.H. holds membership on an entity's board of directors or advisory committees and speakers bureau for Novartis. A.G. received speaker honoraria from Roche, Janssen, Abbvie, Celgene, Fresenius, and Novo Nordisk; travel and accommodation expenses from Roche, Janssen, and Abbvie. T.C.E. ended employment in the past 24 months with Roche; received speaker fee from Abbvie. C.Y.C. provided consultancy, received honoraria and other (advisory) for/from Roche, Janssen, MSD, Gilead, Ascentage Pharma, Beigene, AstraZeneca, Loxo/Lilly, and TG Therapeutics; received research funding from Abbvie and Celgene. A.J.M.F. has membership on an entity's board of directors or advisory committees for Gilead, Novartis, Juno, PletixaPharm, Roche, and Incyte; received research funding from BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, and Pfizer. C.P.F. received honoraria and has membership on an entity's board of directors or advisory committees and received research funding for/from Roche; received speaker fees from Janssen. K.C. provided consultancy and received travel expenses to scientific conferences and speakers bureau for/from Roche, Janssen, Kite/Gilead, and Takeda; provided consultancy and speakers bureau for Gilead and Incyte; provided consultancy for Celgene and Atara; received travel expenses to scientific conferences for BMS/Celgene. P.M. received honoraria and has membership on an entity's board of directors or advisory committees from/for Roche, Kite, Takeda, and Beigene; received travel support from Gilead and Janssen. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2022 American Society of Hematology
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology