The Age, Comorbidities and Albumin (ACA) Index Is Independently Associated with Overall Survival in Patients with Mantle Cell Lymphoma (MCL)

Background: Mantle cell lymphoma (MCL) is a biologically and clinically heterogenous disease with variable outcomes. Numerous prognostic factors have been identified, including blastoid histology, the MCL International Prognostic Index (MIPI) score, high proliferation index, TP53 deletions and/or mutations, complex karyotype, minimal residual disease positivity, and several others. Most prognostic scores do not take patient characteristics into account and require additional testing which may not be routinely available. In particular, older adults have heterogenous outcomes due to the presence of comorbidities, impaired functional and/or nutritional status which is not factored into the MIPI score. The age, comorbidities and albumin (ACA) index is a simple score that can be gleaned from the electronic health record either in real-time or retrospectively and has been validated in patients with diffuse large B cell lymphoma. We evaluated the impact of the ACA index on outcomes in patients with MCL.

Methods: The Roswell Park MCL database includes all patients with MCL evaluated at Roswell Park Comprehensive Cancer Center from 2007 to 2019. A serum albumin (SA) level of <3.7 g/dL was defined as "low". The age, comorbidities and albumin (ACA) index included a low SA level, age ≥ 75 years, and a Charlson comorbidity index (CCI) score of ≥3 (representing moderate to severe comorbidity burden), with each variable when present contributing to a score of 1. A score of 0 was defined as "excellent", 1 as "good", 2 as "moderate" and 3 as "poor". The log-rank test was used to compare overall survival (OS), and the Cox-proportional hazard model was used for univariate (UVA) and multivariate (MVA) survival analyses.

Results: A total of 245 patients with a median age of 64 years [interquartile range (IQR), 56-73 years] were included in the study, with a median follow-up of 90.2 months (95% CI, 75.1 - 107 months). Overall, 111 (45%) patients were age ≥65 years, 81 (33.1%) were age ≥70 years, and 44 (18.0%) were age ≥75 years; 73% of patients were male, and 11 patients had an ECOG PS ≥2. Older adults (age ≥75 years) had a greater burden of comorbidities (CCI≥3, p<0.001), and poor PS (ECOG ≥2, p=0.006) compared with younger patients. The median SA in the entire cohort was 4.30 g/dL (IQR 3.90, 4.50), with lower median levels in patients age ≥75 versus age <75 years (4.00 vs 4.35, p<0.001); however, there was no difference in frequency of patients with low SA levels (<3.7 g/dL) (19% vs 14%, p=0.4). A low SA level, CCI≥3, high or intermediate MIPIb risk, ki-67>30%, and increased age (≥75 years) were significantly associated with inferior OS. Patients who received an autologous or allogeneic stem cell transplant (SCT) in any line of therapy had improved OS (HR 0.5517, p=0.001). The ACA score could be calculated in 69.8% of patients- 58% of patients had an excellent ACA score (0), 30% of patients had a good score (1) and 9.9% of patients had a moderate score (2). Only 2 (1.2%) patients had a poor score (3). Patients with higher ACA scores had significantly inferior OS (HR 2.117, p<0.0001). In a MVA that adjusted for MIPIb risk and treatment with SCT in any line, this risk remained significant (HR 1.67, p=.007).

Conclusion: A simple, patient-factor based scoring system incorporating hypoalbuminemia and the presence of comorbidities is strongly predictive of survival in patients with MCL, irrespective of disease stage, MIPIb risk score, and known molecular risk factors. Further steps include validation of the ACA index in an independent MCL cohort and incorporation of elements from the ACA index into known prognostic models to develop a new score that takes both disease biology and patient physiology into account.

Ghione:AstraZeneca Pharmaceuticals: Consultancy; Kyowa Hakko Kirin: Consultancy; Kite Pharma: Research Funding; Secura Bio: Consultancy. Torka:Targeted Oncology, Physician Education Review: Honoraria; Epizyme: Consultancy; Lilly USA: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Genentech: Consultancy.