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. 2024 Dec 24;8(24):6195-6206.
doi: 10.1182/bloodadvances.2024013780.

Evolving consolidation patterns and outcomes for a large cohort of patients with primary CNS lymphoma

Kathryn R Tringale  1   2 , Michael Scordo  3 , Joachim Yahalom  1 , Charlie White  4 , Zhigang Zhang  4 , Javin Schefflein  5 , Gustav Cederquist  1 , Lauren R Schaff  6 , Lisa DeAngelis  6 , Brandon S Imber  1 , Christian Grommes  6
Affiliations

Evolving consolidation patterns and outcomes for a large cohort of patients with primary CNS lymphoma

Kathryn R Tringale et al. Blood Adv. .

Abstract

Consolidation for primary central nervous system lymphoma (PCNSL) after induction chemoimmunotherapy include whole-brain radiotherapy (WBRT; ≤24 Gy reduced-dose [RD], >24 Gy standard-dose) and cytarabine, nonmyeloablative chemotherapy (NMC), or autologous hematopoietic cell transplantation (AHCT). Comparative outcomes are lacking. Outcomes from 1983-2020 were stratified by decade and Memorial Sloan Kettering Cancer Center recursive partitioning analysis (RPA) class. Clinicodemographic associations were analyzed by multinomial logistic regression. Progression-free survival (PFS) and overall survival (OS) were analyzed by proportional hazards. Of 559 patients, 385 (69%) were consolidated. Median follow-up and OS were 7.4 and 5.7 years, respectively. WBRT use declined (61% (1990s) vs 12% (2010s)), whereas AHCT (4% (1990s) vs 32% (2010s)) and NMC (27% (1990s) vs 52% (2010s)) rose. Compared with RPA 1, RPA 2 was more likely to receive NMC. Those with partial response to induction were less likely to receive AHCT (odds ratio, 0.36; P = .02). Among 351 with complete response to consolidation, only receipt of rituximab, methotrexate, procarbazine, and vincristine induction was associated with improved PFS (hazard ratio, 0.5; P = .006). Among RPA 1, median PFS and OS were not reached for AHCT or RD-WBRT, vs 2.5 and 13.0 years, respectively, after NMC. Among RPA class 3, median PFS and OS after RD-WBRT were 4.6 and 10 years, vs 1.7 and 4.4 years after NMC. No significant adjusted survival differences were seen across consolidation strategies. NMC is increasingly used in lieu of RD-WBRT despite a trend toward less favorable PFS. RD-WBRT can be considered in patients ineligible for AHCT.

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Conflict of interest statement

Conflict-of-interest disclosure: M.S. served as a paid consultant for McKinsey & Company, Angiocrine Bioscience Inc, and Omeros Corporation; received research funding from Angiocrine Bioscience Inc, Omeros Corporation, and Amgen Inc; served on ad hoc advisory boards for Kite (a Gilead company); received honoraria from i3Health, Medscape, and CancerNetwork for CME-related activity; and received honoraria from IDEOlogy. L.R.S. reports scientific advisory board participation for BTG, plc; reports research funding from BTG, plc, Merck, and DebioPharm; reports consultant fees from ONO; and has a patent pending related to the use of low-dose glucarpidase. B.S.I. reports professional services related to GT Medical Technologies Inc, Ono Pharma, and Telix Pharmaceuticals Limited (uncompensated); and receives research funding outside this work (to the institution) from AstraZeneca, Novartis, Bayer, and Kazia Therapeutics. C.G. reports consulting services from BTG International, Curis, Ono Pharma, and Roche; and reports speakers bureau services for Ono Pharma and Curis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Progression-free (PFS) and overall survival (OS) based on MSK RPA class. (A) PFS and (B) OS.
Figure 2.
Figure 2.
Change in consolidation regime over time. (A) Stacked bar with proportion of consolidation approach by decade. There was significant change in consolidation with declining use of WBRT plus cytarabine (61% in 1990s vs 12% in 2010s) and rising use of AHCT (4% in 1990s vs 32% in 2010s) and cytarabine (27% in 1990s vs 52% in 2010s; Fisher exact test, P value <.001). (B) Consolidation approach in the 1980s stratified by RPA class. (C) Consolidation approach in the 1990s stratified by RPA class. (D) Consolidation approach in the 2000s stratified by RPA class. (E) Consolidation approach in the 2010-2020s stratified by RPA class.
Figure 3.
Figure 3.
PFS and OS on 6-month postconsolidation landmark analysis. Receipt of any consolidation strategy was associated with both improved PFS and OS compared with no consolidation strategy (log-rank P < .001).
Figure 4.
Figure 4.
PFS and OS by consolidation strategy stratified by RPA class among patients who achieved CR/CRu to consolidation. In patients who received cytarabine alone, median OS was 7.7 years for RPA class 2 and 4.4 years for RPA class 3. In patients who received RD-WBRT, median OS was 13.0 years for RPA class 2 and 10.0 years for RPA class 3. In patients who received AHCT median OS was 9.4 years for RPA class 2 and 1.1 years for RPA class 3.
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