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3595 Improving the Utilization and Tolerability of Thiotepa-Based Autologous Stem Cell Transplantation in Primary CNS Lymphoma

Program: Oral and Poster Abstracts
Session: 731. Autologous Transplantation: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
adult, Research, Biological therapies, Non-Biological therapies, Lymphomas, health outcomes research, B Cell lymphoma, Chemotherapy, Clinical Research, Diseases, Therapies, aggressive lymphoma, real-world evidence, Lymphoid Malignancies, Study Population, Human, Transplantation
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Robert Puckrin, MD1, Colin Stewart, MD2, Carolyn Owen, MD3, Lesley E. Street, MD2*, Sarah Perry, MD2*, Peter Duggan, MD2, Mona Shafey, MD2, Neil Chua, MD4* and Douglas A. Stewart, MD2*

1Tom Baker Cancer Centre and University of Calgary, Calgary, AB, Canada
2Tom Baker Cancer Centre and University of Calgary, Calgary, Canada
3Tom Baker Cancer Centre, Calgary, AB, Canada
4Cross Cancer Institute and University of Alberta, Edmonton, Canada

Background: Thiotepa-based autologous stem cell transplantation (ASCT) improves survival in primary central nervous system lymphoma (PCNSL) but up to 30-60% of patients are unable to receive ASCT after MATRix induction, frequently due to treatment-related adverse events. Common conditioning regimens such as thiotepa/BCNU or thiotepa/busulfan/cyclophosphamide have also been associated with risks of pulmonary toxicity or increased transplant-related mortality. Novel strategies to improve the utilization and tolerability of ASCT are therefore needed to maximize the curative potential of this therapy in PCNSL.

Methods: This retrospective population-based study included all patients diagnosed with large B-cell lymphoma-type PCNSL who were intended for ASCT in the province of Alberta, Canada between 2011 and 2022. Provincial treatment guidelines recommended an abbreviated, low-intensity induction protocol to reduce toxicity and increase transplantation rates (Figure 1B). Step 1 included 2 cycles of rituximab/high-dose methotrexate (HD-MTX). Step 2 involved 1 cycle of rituximab/high-dose cytarabine (HDAC) for peripheral blood stem cell mobilization. Step 3 consisted of 2 cycles of rituximab/HD-MTX/HDAC and was made optional in July 2018 so that patients with sufficient disease response and performance status following Step 2 could proceed immediately to ASCT. Conditioning consisted of thiotepa 300 mg/m2 ×2 days and busulfan 3.2mg/kg ×3 days (TT/Bu). Dose reductions of TT/Bu by 10% for every 5 years over the age of 60 were recommended as of May 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and compared between groups using the log-rank test.

Results: The intention-to-transplant (ITT) cohort included 71 patients with median age 58 years (range 26-72), representing 81% of patients aged 18-60 and 55% of those aged 61-72 who were diagnosed with PCNSL in Alberta during the study period. The proportion of patients aged 61-72 who were treated with ITT increased from 42% before 2018 to 70% afterwards.

Fifty-six (79%) ITT patients proceeded to ASCT while 15 (21%) did not due to poor performance status (n=6), treatment-related adverse events (n=5), or disease progression (n=4). There was 1 (1%) death due to infection-related non-relapse mortality (NRM) during induction. The routine omission of Step 3 starting in 2018 resulted in high transplantation rates at 29/35 (83%) compared to 27/36 (75%) in the preceding era.

With median follow-up time 3.9 years, the 4-year PFS was 69% (95% CI 56-79%) and OS was 80% (95% CI 67-88%) in the ITT cohort (Figure 1A). For the 56 patients who received ASCT, 4-year PFS was 75% (95% CI 57-86%) and OS was 85% (95% CI 68-93%) from the time of ASCT. There was no significant difference in PFS between patients in complete response (CR)/unconfirmed CR versus partial response (PR) before ASCT (p=0.86); however, 5 patients with progressive disease before ASCT had inferior PFS compared to those with CR/CRu/PR (4-year PFS 40% vs 82%, p=0.0002). Relapse occurred in 8 (14%) patients at median 373 days (range 54-1411) after ASCT, including 7 with CNS relapse and 1 with systemic relapse. No patient in remission after ASCT received whole brain radiation therapy and most recovered without clinically significant neurologic deficits. There were no deaths due to transplant-related mortality. NRM occurred in 2 (4%) patients due to an unrelated cancer and stroke 1.1 and 4.3 years after ASCT, respectively.

Among 27 patients >60 years old treated with ITT, 17 (63%) proceeded to ASCT, including 6 who received dose reductions of TT/Bu. The transplantation rate in this age group increased from 45% to 75% following the routine omission of Step 3. All 17 transplanted patients remain alive and in remission with median follow-up 2.5 years.

Conclusion: In this real-world study of 71 patients with PCNSL, an abbreviated, low-intensity induction protocol resulted in high transplantation rates (~80%) and favorable long-term outcomes with 4-year OS 80%. Notably, TT/Bu conditioning achieved a low incidence of relapse with no transplant-related mortality observed, including among patients >60 years old. These data demonstrate that de-escalated induction therapy can result in improved rates of successful ASCT, thereby optimizing the outcomes of PCNSL.

Disclosures: Puckrin: Kite: Honoraria; Beigene: Honoraria; Incyte: Honoraria. Owen: F. Hoffmann-La Roche Ltd, AbbVie, Astrazeneca, Beigene, Merck, Incyte, Seattle Genetics, Novartis: Honoraria. Street: Seattle Genetics: Honoraria; Recordati: Honoraria; Kyowa Kirin: Honoraria. Perry: Beigene: Honoraria; Novartis: Honoraria; Seattle Genetics: Honoraria; Sobi: Honoraria; Incyte: Honoraria. Shafey: AstraZeneca: Honoraria; Roche: Honoraria. Stewart: Amgen: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Sandoz: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria; Roche: Honoraria; Teva: Honoraria.

*signifies non-member of ASH