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3599 Long-Term Remissions after First-Line Autologous Stem Cell Transplantation for Mantle Cell Lymphoma

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

Colin Stewart, MD1*, Carolyn Owen, MD2, Neil Chua, MD3*, Anthea Peters, MD3, Mona Shafey, MD1, Douglas A. Stewart, MD1* and Robert Puckrin, MD4

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

Introduction: The role for autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL) has been recently called into question by the TRIANGLE trial, which demonstrated similar 3-year outcomes with or without ASCT among patients treated with R-CHOP/R-DHAP and 2 years of maintenance ibrutinib +/- rituximab. However, long-term follow-up is necessary to determine the durability of remissions and ascertain the true value of first-line ASCT for MCL.

Methods: This retrospective population-based study included all patients ≥18 years old who received ASCT as part of first-line therapy for MCL in the province of Alberta, Canada between 2000-2022. The primary objective was to determine freedom from progression (FFP), which was measured from the time of ASCT to disease progression. Secondary objectives were to determine progression-free survival (PFS) and overall survival (OS). FFP, PFS, and OS were estimated using the Kaplan-Meier method. Cumulative incidences of relapse and non-relapse mortality (NRM) were determined using competing risks analysis. Univariable and multivariable Cox regression was performed to identify risk factors for FFP.

Results: The study population included 141 patients with median age at ASCT of 60 years (range 34-71). At diagnosis, 130 (92%) patients had advanced stage disease, 52 (37%) had intermediate/high risk MIPI score, 35 (25%) had Ki67 >30%, 32 (23%) had B symptoms, and 17 (12%) had blastoid/pleomorphic histology. Induction protocols included R-CHOP/cytarabine combinations (n=93), R-bendamustine/cytarabine combinations (n=36), or alternative regimens (n=12). PET-defined pre-transplant disease status was complete metabolic response in 75 (82%) and partial metabolic response in 17 (18%) patients. ASCT conditioning consisted of melphalan plus total body irradiation (n=93), BEAM (n=40), or other regimens (n=8). Maintenance rituximab was received by 96 (68%) patients.

With median follow-up time 7.6 years (range 0.4-23.2), the median FFP was not reached (Figure 1) while the median PFS was 11.3 years and median OS was 14.0 years. At 8 years after ASCT, FFP was 67% (95% CI 56-75%), PFS was 57% (95% CI 46-66%), and OS was 70% (95% CI 60-78%). FFP at 8 years was 76% (95% CI 59-86%) with maintenance rituximab versus 49% (95% CI 33-63%) without maintenance rituximab (p<0.001). Multivariable analysis revealed that maintenance rituximab was associated with improved FFP (HR 0.26, 95% CI 0.10-0.72) and B symptoms were associated with inferior FFP (HR 8.45, 95% CI 2.86-25.0), whereas age, Ki67, blastoid/pleomorphic histology, and MIPI score were not significantly associated with FFP.

The cumulative incidence of relapse at 8 years was 32% (95% CI 23-41%) and the mean relapse rate appeared to decrease over time, from 4.4%/year during years 0-5 to 2.5%/year during years 6-12 after ASCT. In a subgroup analysis to evaluate the very long-term outcomes of 49 patients who underwent ASCT >10 years ago, median follow-up time was 12.5 years (range 0.4-23.2) and 13-year FFP was 40% (95% CI 26-54%), PFS was 32% (95% CI 19-46%), and OS was 54% (95% CI 35-68%). No relapse occurred >11.2 years after ASCT. Twenty patients remain alive and in remission for >10 years, 5 patients for >15 years, and 1 patient for >20 years after ASCT. There were no cases of NRM within 1 year of ASCT. Therapy-related myeloid neoplasms occurred in 3 (2%) patients.

Conclusions: This long-term follow-up study demonstrates that first-line ASCT frequently achieves durable remissions in MCL, with median PFS >11 years, a declining relapse rate over time, and notably high FFP rates among those who receive maintenance rituximab. A subset of patients experienced remissions lasting >10-20 years and may be functionally cured of their lymphoma, although additional follow-up is warranted to confirm the emergence of a plateau on the FFP curve. Given the durability of remissions and possibility of cure in some patients, longer follow-up of the TRIANGLE trial should be awaited before first-line ASCT is prematurely abandoned for MCL.

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

*signifies non-member of ASH