Multicohort Study of Conditional Survival and Cause of Death After Achieving Event-Free Survival at 24 Months (EFS24) in Patients With Mantle Cell Lymphoma (MCL)

Background: MCL is considered incurable, but outcomes are improving in the evolving treatment landscape. Event-free survival status at a landmark (e.g., 24 months) after frontline IC may help identify patients who will subsequently do well, which would be useful for patient counseling, care planning, and trial design. We evaluated conditional survival and cause of death in MCL patients who achieve EFS24 after frontline immunochemotherapy (IC). Methods: Outcomes after frontline IC were evaluated in 3 cohorts: Mayo/Iowa MER prospective clinic-based cohort, BC Cancer retrospective population-based cohort, and Swedish Lymphoma Register. For each cohort, 2 treatment eras were defined based on the specifics of local treatment patterns (Figure 1 A). Overall survival (OS) after diagnosis and after achieving EFS24 was compared to the background age and sex matched general population using a standardized mortality ratio (SMR). Cumulative incidences of cause-specific deaths were analyzed using a competing risk model. Results: In the MER, patients treated in Era M1 (2002–2009; n = 110) and M2 (2010–2015; n = 127) both had inferior OS compared to the US general population. A lower SMR (2.43 vs. 3.95) in Era M2 suggested a narrower gap in OS versus the general population. Lymphoma was the leading cause of death in both eras. In Era M1, patients achieving EFS24 still had inferior OS compared to the general population (SMR = 2.81, 95% CI: 1.98–3.88), and lymphoma remained the leading cause of death. However, in Era M2, patients achieving EFS24 had similar OS compared to the general population (SMR = 1.35, 95% CI: 0.83–2.09), and lymphoma was no longer the leading cause of death (Figure 1 B&E). In the BC cohort, patients treated in Era B2 (6/2013–2019; n = 188) versus Era B1 (2003–5/2013; n = 250) had a narrower gap in OS compared to the British Columbia population (SMR 4.53 vs. 6.69). Lymphoma was the leading cause of death in both eras. For patients achieving EFS24, the gap in OS was narrower in Era B2 versus B1 (SMR 3.56 vs. 4.99). After achieving EFS24, lymphoma was the leading cause of death for patients in Era B1 but not in Era B2 (Figure 1 C&E). Similar results were seen in the Swedish cohort. The gap in OS compared to the general Swedish population was narrower in Era S2 (2013–2018; n = 439) vs. S1 (2006–2012; n = 442), both after frontline IC (SMR 4.8 vs. 5.4) and after achieving EFS24 (SMR 2.6 vs. 3.4). After achieving EFS24, lymphoma was the leading cause of death for patients in Era S1 but not in Era S2 (Figure 1 D&E). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. Y. Wang Consultant or advisory role: Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene (all compensation to my institution) Honoraria: Kite (to my institution) Research funding: Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab (all to my institution) B. K Link Consultant or advisory role: Genentech, MEI Inc V. Diego Consultant or advisory role: Janssen, BeiGene, AstraZeneca, Merck, Kite/Gilead, BMS/Celgene, AbbVie, ONO therapeutics, Zetagen, Roche Honoraria: Janssen, BeiGene, AstraZeneca, Merck, Kite/Gilead, BMS/Celgene, AbbVie, ONO therapeutics, Zetagen, Roche Research funding: Roche, AstraZeneca (to institution)