Social Factors May Interfere With Transplant, Decreasing Survival in MCL

According to a new study, marital status and education level may impact treatment and overall outcomes for patients with mantle cell lymphoma.

Consolidation with autologous hematopoietic cell transplantation (AHCT) was less often given to patients with mantle cell lymphoma (MCL) from certain social and educational backgrounds, ultimately contributing to an increased mortality rate, according to a real-world study conducted in Sweden.1

“A surprisingly high proportion of younger (<65 years) MCL patients (40%) were not treated with AHCT as part of their primary treatment. Factors associated with a lower likelihood of being selected to an AHCT included higher age, being never married or divorced, having any comorbidity, and lower socioeconomic status. We also noted survival disadvantages for non–AHCT-treated patients, implying that these selection mechanisms may have prognostic implications,” wrote the study authors led by Ingrid Glimelius, MD, PhD, of Uppsala University.

The trends of AHCT and its correlation with mortality have been studied in the United States (NCT03267433) as well.2 In a large cohort of younger patients with MCL who have undergone AHCT, the study showed that AHCT after induction therapy was associated with prolonged progression-free survival (PFS), and the investigators, therefore, recommended consolidation with AHCT for the subgroup. Later, in a study conducted by the Nordic Lymphoma Group, a significant improvement in PFS and modest improvement in overall survival (OS) was observed in older patients who underwent autologous stem cell transplant after rituximab (Rituxan) in combination with ibrutinib (Imbruvica), and cytarabine-containing induction.3

Based on the modest OS improvement in patients with MCL following AHCT, little is known about how AHCT impacts survival, warranting new research like the registry study conducted in Sweden.1

Patients included in the study we identified through the Longitudinal Integrated Database for Health Insurance and Labor Market Studies in Sweden. The patients were characterized by education of ≤9 years to >12 years and civil status of married, never married, divorced, or widowed. The group of 413 patients enrolled were diagnosed with MCL between January 2000 and June 2014 and were all between the ages of 18 and 65 years old. A total of 44 patients were excluded from the analysis, leaving 369 patients in the final cohort. Of the patients evaluated, 221 had undergone AHCT within 18 months and 148 had not.

Prediction of the probability of death in the patients enrolled was categorized as either alive without AHCT, alive with AHCT, dead before AHCT, or dead after AHCT. Patients were evaluated according to the time scale of time since MCL diagnosis.

In the group of patients who had AHCT, the majority were married (63.8%), but 17.7% had never been married, 16.7% were divorced, and 1.8% were widowed. The bulk of the AHCT cohort had 10 to 12 years of education, while 15.8% had up to 9 years, and 30.8% attended 12 years of school or more. Education data were unavailable for 2.7% of the AHCT cohort.

Among the patients who did not undergo AHCT within 18 months, 50.7% were married, 19.6% were never married, 24.3% were divorced, and 5.4% were widowed. This non-transplanted cohort had 42.6% of patients with 10 to 12 years of education, 30.4% with up to 9 years of education, and 23.7% with 12 years of education or more. Information about education was missing for 3.4% of this group.

The results showed that a total of 5 patients out of 221 who underwent AHCT died within 100 days, which showed that transplant-related mortality was low. During follow-up, another 145 patients with MCL died. Seventy-eight percent of the deaths during follow-up were lymphoma related. Overall, undergoing AHCT was associated with reduction in all-cause mortality compared with no AHCT (HR, 0.58; 95% CI, 0.40-0.85), according to the multivariate Cox analysis.

Notably, the mortality reduction was consistent regardless of age for patients who received AHCT versus those who did not (P > .05). Use of cytarabine in the induction setting did not significantly impact all-cause mortality in patients who underwent AHCT compared with the no-AHCT group (HR, 1.01; 95% CI, 0.56-1.80). The difference in mortality in patients who underwent AHCT versus those who did not after being treated with chlorambucil, watch and wait, or radiotherapy alone was reduced by 52% (HR, 0.48; 95% CI, 0.32-0.71). Taken together, these findings showed that receipt of AHCT improved the prognosis in comparison to non-AHCT treatment regimens.

Further, an analysis of OS in the study looked into the number of patients who died following AHCT in each age group. The 10-year OS rate was 57% for patients aged 49 or younger, 52% for those aged 50 to 59, and 32% for the 60 to 65 group. Patients in the youngest age group were notably more likely to undergo AHCT and remain alive.

In the older group of patients (age 66-70), there were no deaths in the first 100 days after AHCT, similar to what was observed in the younger group. Receipt of AHCT in the older patients reduced the mortality rate compared with not having AHCT.

Survival was impacted by social status and education level. Overall, being a widower increased all-cause mortality compared with being married (HR, 2.76; P = .01), and having a lower education level increased morality compared with a higher education level (HR, 1.57; P = .018). Looking at those who received AHCT and were widowers compared with the married population, there was still an increased mortality rate for widowers, however, it was not significant (HR, 2.76; P = .43). For those with lower education who underwent AHCT versus those with higher education who underwent AHCT, the HR for the difference was 1.16 (P = .28).

“This calls for the need of a more informed decision making in relation to not only the patients’ health prior to AHCT but also their sociodemographic situation. In case an AHCT is deemed impossible, integration of novel treatment concepts instead or in combination with standard treatment is needed,” wrote Glimelius et al.

References:

1. Glimeius I, Smeby KE, Albertson-Lindbald A, et al. Unmarried or less-educated patients with mantle cell lymphoma are less likely to undergo a transplant, leading to lower survival. Blood Adv. 2021;5(6):1638-1647. doi:10.1182/bloodadvances.2020003645

2. Gerson JN, Handorf E, Villa D, et al. Survival outcomes of younger patients with mantle cell lymphoma treated in the rituximab era. J Clin Oncol. 2019;37(6):471-480. doi:10.1200/JCO.18.00690

3. Abrahamsson A, Albertsson-Linbald A, Brown PN, et al. Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study. Blood. 2014;124(8):1288-1295. doi:10.1182/blood-2014-03-559930