Long-Term Outcomes of Autologous Hematopoietic Cell Transplant of Multiple Myeloma: A 10 Year Follow up Study

Introduction: Multiple myeloma (MM) is a disorder of plasma cell proliferation that affects 1 in 132 humans in the United States. While the disease is generally characterized by good initial response rates, the majority of MM patients eventually relapse. Autologous Hematopoietic Cell Transplantation (AHCT) is the current standard of care for patients who demonstrate response to initial therapy; however, long-term studies looking at the association between certain demographic, clinical and cytogenetic factors with long-term outcomes post-AHCT are scarce. We report herein our AHCT outcomes over the past 10 years.

Methods: We retrospectively reviewed the electronic medical records of all MM patients who underwent AHCT at Cleveland Clinic between January 1^st, 2011 and January 15^th 2021. Demographic characteristics, time to transplant, cytogenetic risk, International Scoring System (ISS), labs, lines of treatment, response (per International Myeloma Working Group criteria), overall survival and progression free survival were collected through chart review. Cox proportional hazards regression analysis using the Statistical Package for Social Sciences (SPSS) was performed to determine factors that significantly and independently affect relapse and overall survival. Kaplan-Meier analysis was performed to compare the median overall survival (mOS) and median progression free survival (mPFS) according to the cytogenetic risk.

Results: A total of 517 patients with median follow up of 32.9 months were included, of whom FISH cytogenetics and ISS were available in 413 and 424, respectively. Our cohort had a median age at AHCT of 60.2 years and male preponderance of 58.2%. ECOG performance status was 0 in 158 (30.6%), 1 in 321 (62.2%), 2 in 36 (7%) and 3 in 1 (0.2%) at AHCT. Of patients with available ISS, 160 (37.7%) had stage I, 165 (38.9%) had stage II and 99 (23.3%) had stage III. Standard risk (SR) and high risk (HR) FISH were present in 279 (67.6%) and 134 (32.4%) patients, respectively, and the most common abnormalities were del (13q) (33.9%) followed by t(11;14) (22.0%), gain 1q (18.2%), del(17p) (10.7%) and t(4;14) (7.7%). Most patients had IgG (68.9%) followed by IgA (23.5%) MM. Median lines of treatment pre-AHCT was 1 (range 1-9), while 132 (25.5%) had complete response (CR), 176 (34%) had very good partial response (VGPR), and 209 (40.4%) had partial response (PR) pre-AHCT. Looking into factors affecting outcomes, our analysis suggested that HR cytogenetics (HR 2.34, 1.34-4.03 95% CI, P=0.003) and treatment lines of ≥2 pre-AHCT (HR 1.35, 1.03-1.7 95% CI, P=0.024) were independent risk factors for lower OS. In contrast, age at AHCT (HR 1.04, 0.98-1.04 95% CI), male sex (HR 1.05, 0.63-1.73 95% CI), white ethnicity (vs African American HR 1.23, 0.49-3.08 95% CI; vs Other ethnicities HR 1.19, 0.16-9.00 95% CI), time to transplant of ≥12 months (HR 1.35, 0.77-2.39 95% CI), ISS stage III (vs stage I HR 0.94, 0.49-1.82 95% CI; vs stage II HR 1.29, 0.69-2.39 95% CI), and PR disease status pre-ASCT (vs VGPR HR 1.26, 0.71-2.2 95% CI; vs CR HR 1.46, 0.68-3.12 95% CI) did not significantly influence OS. On the other hand, HR cytogenetics (HR 3.12, 2.09-4.66 95% CI, P<0.0001), smoking history (vs never smokers HR 1.51, 1.12-2.04 95% CI, P=0.006) and PR disease status pre-AHCT (vs CR HR 2.11, 1.25-3.56, P=0.005; vs VGPR HR 1.19, 0.81-1.74 95% CI) were found to be independent risk factors for earlier relapse, as opposed to the rest of the factors similarly analyzed for OS. We then focused our Cox model on determining specific HR cytogenetic features that independently affect either OS or PFS. Our results suggested that t(14;16) (HR 3.93, 1.94-7.97 95% CI, P<0.0001), followed by del(17p) (HR 2.75, 1.51-5.00 95% CI, P=0.001) and t(4;14) (HR 2.10, 1.17-3.77 95% CI, P=0.013) independently lower OS. Similarly t(14;16) (HR 5.05, 2.83-8.99 95% CI, P<0.0001), del(17p) (HR 3.49, 2.23-5.44 95% CI, P<0.0001), t(4;14) (HR 2.46, 1.56-3.88 95% CI, P<0.0001) as well as gain (1q) (HR 2.32, 1.54-3.51 95% CI, P=0.009) independently lower PFS. Kaplan Meier-based survival analysis further confirmed a lower mOS (67.4 months vs unreached, P<0.0001) (Fig 1A) and mPFS (21.9 vs 64.2 months, P<0.0001) (Fig 1B) for HR vs SR cytogenetics.

Conclusion: OS post-AHCT in MM patients is mainly affected by HR cytogenetics and number of treatment lines pre-AHCT. HR cytogenetics affects PFS as well, which is also influenced by a smoking history and the pre-AHCT disease status.

Winter:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Seagen, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jagadeesh:Affimed: Membership on an entity's Board of Directors or advisory committees; ATARA Biotherapeutics: Research Funding; Debio pharma: Research Funding; MEI Pharma: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seagen: Research Funding; AstraZeneca: Research Funding; Trillium Pharmaceuticals: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding; LOXO Pharmaceuticals: Research Funding. Sauter:Karyopharm Therapeutics Inc.: Consultancy; Ono Pharmaceuticals: Consultancy; CSL Behring: Consultancy; Gamida Cell: Consultancy; BMS: Other: PI; Precision Biosciences: Other: PI; Genzyme/Sanofi: Other: PI; Kite Pharma Inc.: Consultancy. Hamilton:Syndax: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Kadmon: Membership on an entity's Board of Directors or advisory committees. Hill:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Research Funding. Valent:Alexion, AstraZeneca Rare Disease: Research Funding.