Consolidation (Cons) and maintenance (Maint) approaches in primary central nervous system lymphoma (PCNSL) after high-dose methotrexate induction in transplant-ineligible patients
Year: 2025
Type: conference-abstract
Abstract: Background PCNSL is a rare, aggressive non-Hodgkin lymphoma that primarily affects older adults. Standard treatment involves high-dose methotrexate (HD-MTX)–based induction followed by Cons and/or Maint. Autologous stem cell transplant is preferred, but many are ineligible due to age, comorbidities, or functional limitations. In this group, post-induction strategies are heterogeneous, and real-world outcomes are poorly characterized. We examined Cons and Maint approaches and associated outcomes in transplant-ineligible PCNSL across multiple institutions. Methods We conducted a retrospective study of transplant-ineligible patients with newly diagnosed PCNSL treated with HD-MTX-based induction (2010–2024) at 12 U.S. academic centers. Transplant ineligibility was determined by the treating physician. Eligible patients had at least stable disease post-induction and received Cons or Maint therapy. Clinical data, treatments, and toxicities were collected. Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier methods; and multivariable Cox models assessed prognostic factors. Results Among the 191 included patients, at diagnosis: median age was 69 (range 36–87); 41% had ECOG ≥2, and 39% had geriatric syndromes (e.g., dementia, delirium, depression, osteoporosis, incontinence). Impaired activities of daily living were reported in 24%. Reasons for transplant ineligibility included age (21%), comorbidities/poor function (21%), combined age and functional decline (14%), patient preference (13%), and lack of social support/insurance (5%). Leptomeningeal disease was present in 13%, and 53% had ≥2 parenchymal sites. Neurologic symptoms included motor deficits (60%), cognitive changes (52%), and seizures (8%). Induction regimens included 1) HD-MTX, temozolomide, and rituximab (MTR, 36%); 2) HD-MTX, procarbazine, and vincristine (MPV/variants, 33%); 3) HD-MTX, rituximab (25%); 4) HD-MTX alone/other (4%). Post-induction responses were complete response (CR, 62%), partial response (PR, 29%), and stable disease (SD, 4%). Cons was given to 65% (n=125), Maint to 39% (n=74), and both to 4% (n=8). 77% (n=147) completed intended post-induction therapy determined by the treating physician. Cons regimens included cytarabine (43%), etoposide+cytarabine (25%), radiation (22%), cytarabine+X (8%) and others (2%). Maint included rituximab-based therapy (26%), HD-MTX (22%), temozolomide (18%), BTK inhibitors (BTKi) (16%), HD-MTX+BTKi (3%), lenalidomide (14%) and other (3%). There was strong institutional preference for the use of Cons (P=0.0003 for random-intercept model) and/or Maint (p=0.0039) strategies. Median PFS and OS from start of induction therapy were 69 months (mo) (95% CI, 52–82) and 123 mo (95% CI, 70–141), respectively. Worse OS was associated with lack of CR (p=0.014) and ECOG ≥2 (p<0.001). No significant differences were observed between MTR, MPV, or MR induction in PFS (p=0.25) or OS (p=0.17). For patients receiving Cons, median PFS and OS were 62 (95%CI, 36–76) and 95 (95%CI, 69–not reached [NR]) mo, respectively; for those receiving Maint, median PFS and OS were 78 mo (95%CI, 54–NR) and NR (95%CI, 68–NR), respectively. Comparisons adjusted for age, sex, ECOG, and end-of-induction response showed no significant difference between Cons (p=0.80) and Maint (p=0.33). PFS did not differ among Cons (p=0.90) or Maint (p=0.62) regimens, although BTKi showed a trend toward improved OS compared with HD-MTX (HR=0.10, p=0.058). Of the 59 pts (31%) that have relapsed or progressed, median OS was 10.5 mo (95% CI, 4.5–21). Hospitalizations occurred in 21% (40/191) of patients—14% (17/125) during Cons and 31% (23/74) during Maint—primarily due to infection (35%) and febrile neutropenia (23%). Conclusion In this large, multi-institutional cohort of transplant-ineligible patients with PCNSL, HD-MTX–based induction followed by Cons or Maint yielded more favorable survival outcomes than expected. The strongest prognostic factors for OS were lack of CR after induction and poor baseline performance status. Despite heterogeneous post-induction approaches, outcomes were similar across strategies, and institutional preference largely determined treatment choice, highlighting the absence of standardized care pathways. Given comparable efficacy, lower-intensity, less toxic regimens may be appropriate for this vulnerable population.
Source: Blood
Authors: Yun Kyoung Tiger, Charlotte Zuber, Venkata Preetam Sandeep Kaduluri, Taylor Kujawa, Mollie Reese, Joseph Lukowski, Matthew Gromowsky, Maun Baral, Graham Wehmeyer, Joshua Friedman, Vidiya Srikakulapu, Ross Terada, Mia Willingham, Benjamin Hane, Youssef Youssef, Michele Stanchina, Juan Alderuccio, Timothy Voorhees, Joseph Bennett, Marc Hoffmann, Thomas Ollila, Praveen Ramakrishnan Geethakumari, Adam Kittai, Dilan Patel, Christopher D'Angelo, Chris Dittus, Narendranath Epperla, Cole Sterling, Andrew Evens, Matthew Matasar, Adam Olszewski
Institutions: Rutgers Cancer Institute, Rutgers, The State University of New Jersey, Sidney Kimmel Comprehensive Cancer Center, University of Utah, Huntsman Cancer Institute, University of North Carolina at Chapel Hill, Nebraska Medical Center, University of Nebraska Medical Center, Washington University in St. Louis, Icahn School of Medicine at Mount Sinai, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Brown University, University of Kansas Medical Center, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, University of Miami, Sylvester Comprehensive Cancer Center
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417005100
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