Autologous Stem Cell Transplantation (ASCT) Improves Survival Outcome in Primary Central Nervous System Lymphoma (PCNSL) in a Minority Rich, Underserved Inner City Population in the Real-World Setting

Primary CNS lymphoma (PCNSL) is rare and aggressive with distinct biological features and grim prognosis. Defining optimum treatment for PCNSL is challenging due to a dearth of randomized clinical trials. Autologous Stem Cell Transplant (ASCT) (also referred to as high dose chemotherapy with stem cell rescue) has been recommended by the National Comprehensive Cancer Network (NCCN®) as part of the treatment of PCNSL. There are no comprehensive studies of this disease and therapeutic modalities in real world settings. The aim of our study was to specifically compare the survival outcomes in patients receiving various induction and consolidation regimens used for the treatment of PCNSL.

We sought to study patients with a primary diagnosis of primary CNS lymphoma, treated at our institution from June 2000 to April 2022. Fifty-three unique records of patients with PCNSL patients at Montefiore Medical Center/ Albert Einstein College of Medicine and 32 % (17) patients got ASCT. Mean age at diagnosis was 61 years. Baseline characteristics are in table 1. The most common induction regimen used was RMV (Rituximab, high dose Methotrexate and Vincristine) on 22 patients (41.5% of our cohort), other regimens used are in table 1. Whole brain radiation therapy (WBRT) was used on 2 patients for induction. Consolidation was used in 35 patients (66%). The most common consolidation strategies were: 1) high dose chemotherapy with autologous stem cell support (ASCT) in 17 patients (32%); 2) WBRT in 12 patients (22.6%); 3) Cytarabine (AraC) in 4 patients (7.5%). Eighteen patients (34%) did not receive consolidative therapy while one patient received both cytarabine and WBRT for consolidation. Patients receiving autologous stem cell transplantation were studied based on the conditioning regimen used. The most common regimens used were: 1) Thiotepa, Busulfan and Cytarabine (TBC) in 10 patients (62.5%); 2) BCNU, Etoposide, AraC and Melphalan (BEAM) in 5 patients (31.25%) and BCNU alone in one patient. Table 1 illustrates the comparison of survival outcomes of various consolidation regimens. The mean overall survival in those receiving ASCT was significantly better that patients receiving other consolidation modalities.(p=0.01, depicted in figure 1) We observed that one-year overall survival favored autologous stem cell transplant over WBRT (87% vs 76%). Out of all the patients receiving consolidation with ASCT 14/16 (87.5%) were alive at the time of the last visit [range time from transplant: 161 months - 2 months, median survival after ASCT 30 months]. Notably, WBRT had a remarkable benefit with 9/12 (75%) alive at last follow-up . Patients not receiving consolidative therapy had a worse outcome with 14/21 alive at last follow-up (66.6%) and a significantly worse OS compared to those receiving any consolidation. (58 vs 150 months, p = 0.01). The addition of Rituximab or procarbazine to induction regimens did not result in improved outcomes in survival (p=0.9 and p=0.23 respectively).

In our minority rich urban cohort, we observed that autologous stem cell transplantation consolidation in primary CNS lymphoma resulted in an impressive survival of 87.5% after more than 10 years follow-up. Underutilization of this potentially curative strategy was observed with only 32% having access to autologous SCT. Investigation of the causes precluding transplant access is needed to improve outcomes in this disease.

Bazarbachi:ASH: Research Funding. Konopleva:AbbVie, Genentech, F. Hoffman La-Roche, Stemline Therapeutics, Amgen, Forty-Seven, Kisoji; Janssen: Consultancy; Stocks, Reata Pharmaceuticals: Current equity holder in publicly-traded company; AbbVie, Genentech, F. Hoffman La-Roche, Eli Lilly, Cellectis, Calithera, Ablynx, Stemline Therapeutics, Agios, Ascentage, Astra Zeneca; Rafael Pharmaceutical; Sanofi, Forty-Seven: Research Funding; Forty-Seven; F. Hoffman LaRoche: Honoraria; Reata Pharmaceuticals, Novartis and Eli Lilly: Patents & Royalties; Stemline Therapeutics, F. Hoffman La-Roche; Janssen: Membership on an entity's Board of Directors or advisory committees. Shastri:Janssen: Consultancy; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; NACE: Honoraria; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sica:Curios: Honoraria; AstraZeneca: Honoraria, Research Funding; Bristol Myers Squibb Foundation: Research Funding; Kite Pharma: Research Funding; Miragen: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; PER Physician's Education Review.: Consultancy, Honoraria.