Early Tumor Response Was Associated with Inferior Progression-Free Survival in Newly-Diagnosed Primary Central Nervous System Lymphoma Treated with R-MPV Achieving a Complete Response

Backgrounds

Around 70% of patients with newly diagnosed primary central nervous system lymphoma (PCNSL) achieve a complete response (CR) or complete response unconfirmed (CRu) after methotrexate (MTX) based multiagent chemotherapy. However, the recurrence rate is reported to be around 50% and patient stratification is warranted to identify groups that carry a high risk of recurrence. Early tumor response is associated with long-term outcomes including progression-free survival (PFS) and overall survival (OS) in various cancers including lymphomas, but the prognostic value of early tumor response in PCNSL treated with R-MPV (rituximab, MTX, procarbazine, and vincristine) is not clear. We conducted a retrospective, single-institution study to investigate whether early tumor response was associated with PFS and OS in newly diagnosed PCNSL treated with R-MPV, achieving a CR or CRu.

Methods

Newly diagnosed PCNSL treated with R-MPV at the authors' institution between 2011 and 2022 were identified. Clinical parameters and the number of chemotherapy cycles required to achieve a CR/CRu were assessed. Tumor volumes using contrast-enhanced MRI at two time points: before surgery and first interim analysis after initiation of chemotherapy were measured in whom data were available, and tumor volume reduction rates were calculated. These parameters were analyzed along with PFS and OS.

Results

Ninety-two patients treated with R-MPV were identified, and 68 (75%) patients who achieved a CR/CRu were analyzed in this study. The median age and KPS were 71 and 70, respectively. Among these patients, a median total of seven (range 1-8) R-MPV cycles were delivered. Consolidation whole brain radiation therapy (WBRT) was delivered to 30 younger patients (median age: 63), while 38 older patients (median age: 75) were treated without WBRT. The median follow-up period was 37.9 months. Tumor volumes were assessed in 46 (73%) CR/CRu-achieving patients. The first interim MRI was performed after the first (33/46, 71.7%), second (12/46, 26.1%), and third cycle (1/46, 2.2%) of R-MPV. The median number of cycles required to achieve CR/CRu was five (range 1-8). Requiring six or more chemotherapy cycles to achieve CR/CRu (CR≥6C) was associated with longer PFS in comparison with those who had earlier CR achievement (CR<6C) (median: not reached vs. 87.8 months, p=0.034). In line with these findings, there was a nonsignificant tendency for shorter PFS in patients with a tumor volume reduction rate of over 93% (median: 26.2 vs. 97.1 months, p=0.071). Baseline tumor volume was not associated with PFS or OS. The positive prognostic impact of CR≥6C was greater among patients treated without WBRT (median: not reached vs. 26.2 months, p=0.025), which was further stratified by number of lesions (single/multiple) (CR≥6C, single: median not reached, CR≥6C, multiple: median not reached, CR<6C, single: median 61.4 months, CR<6C, multiple: median 17.9 months, p=0.043). Among these patients, patients with CR≥6C had a nonsignificant tendency to receive the maximum eight cycles of R-MPV compared with those with CR<6C (14/16; 87.5% vs. 12/22; 59.1%, p=0.078).

Conclusion

Early tumor response was not indicative of superior survival outcomes but rather indicative of inferior PFS in newly diagnosed PCNSL treated with R-MPV, especially in patients treated without consolidation WBRT, in this single-center retrospective cohort. These data suggest that reducing the number of cycles from the maximum number of eight cycles might compromise disease control even when early tumor response or early CR is observed, especially in patients with multiple lesions, in newly-diagnosed PCNSL treated with R-MPV. Further investigation in a larger cohort is warranted.

Sasaki:UCB S.A.: Honoraria; Ono Pharmaceutical CO. LTD.: Honoraria. Saito:Daiichi-Sankyo: Honoraria; UCB: Honoraria; Eisai: Honoraria; Medtronic: Honoraria. Nakatomi:Johnson & Johnson: Honoraria; Daiichi-Sankyo: Honoraria. Takayama:Chugai Pharmaceutical Co.,Ltd: Honoraria, Research Funding; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Pfizer: Honoraria; Nippon Shinyaku Co., Ltd: Honoraria; AvvVie GK: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Research Funding. Yokoyama:Canon medical systems co.: Research Funding. Nagane:ONO Pharma: Consultancy, Honoraria, Research Funding; Nippon-Shinyaku: Consultancy; Chugai Pharma: Research Funding; Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa-Kirin: Honoraria, Research Funding; Terumo: Research Funding; Nippon-Kayaku: Honoraria, Research Funding; Asahikasei Medical: Research Funding; Sanei: Research Funding; Ohara Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; UCB: Honoraria; Novocure: Honoraria; Eisai: Honoraria; Servier: Membership on an entity's Board of Directors or advisory committees.