Increased Charlson Comorbidity Index (CCI) Is Not Associated with Inferior Clinical Outcomes in Patients with Mantle Cell Lymphoma (MCL)
Authors: Ridley Derrick , Goyal Subir , Calzada Oscar , Churnetski Michael C , Koff Jean L. , Lechowicz Mary Jo , Flowers Christopher R , Cohen Jonathon B. 
Published: October 2019

Abstract
Introduction
Mantle cell lymphoma (MCL) frequently impacts elderly patients (median age of diagnosis is 68), and management of these patients can be difficult due to the presence of comorbidities in this group. Presence of comorbidities is associated with inferior outcomes in many hematologic malignancies but there has not been a systematic assessment of comorbidities in MCL. We utilized the Charlson Comorbidity Index (CCI) to describe the presence of comorbidities in MCL patients and to explore their impact on patient outcomes.
Methods
We included patients with MCL evaluated at Emory between January 1, 2000 and December 31, 2016. Patients with limited or inadequate follow-up or for whom data to determine the CCI were inadequate were excluded.
We determined the CCI at the time of initiation of treatment for all patients with MCL and excluded "lymphoma" from this calculation. Patients were categorized into severity classes based on their summed scores. The median score of 1 was used to delineate the "low" and "high" CCI groups.
For each group (low and high CCI), we evaluated baseline demographic, clinical and treatment characteristics and identified specific toxicity-related outcomes including: failure to complete induction chemotherapy, unplanned hospitalizations, or treatment related toxicities. Progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and we assessed for the impact of CCI score on PFS and OS using Cox proportional hazards models.
Results
Of 178 patients with MCL, 129 were male (73.3%) and median age was 61 (32-86). One hundred forty patients (86.4%) had stage IV disease. Among the 99 reported values, 31 patients (31.3%) had an elevated LDH, and ECOG PS was 0 in 47 patients, 1 in 66 patients, and 2-4 in 8 patients. Induction therapy was R-HyperCVAD (n=79; 45.4%), R-CHOP (n=49; 28.2%), BR (n=13; 7.5%) RCHOP/RDHAP (n=3; 1.7%) and Other (N=29; 16.7%). The CCI scores for the whole cohort were 0 in 78 pts (43.8%), 1 in 57 pts (32%), 2 in 24 pts (13.5%) and 3+ in 19 pts (10.7%; See Figure 1). One hundred thirty-five patients (75.8%) patients had a low CCI score (0-1) and 43 patients (24.2%) had a high CCI score (>1). Compared to patients with a low CCI, those with high CCI were older (median 67 years vs 59 years, p<0.001), were more likely to have B-symptoms at diagnosis (48% vs 30%, p=0.04) and had a decreased baseline platelet count (median 137 vs 178, p=0.02). Among the 83 patients who completed an intensive induction regimen, that contained high dose cytarabine, 71 (85.5%) had a low CCI and 12 (14.5%) had a high CCI.
Twenty-eight patients experienced an unplanned hospitalization during induction, including 23 in the low CCI group (22%) and 5 in the high CCI group (16%; p=0.49). Seventeen patients de-escalated or discontinued induction therapy prematurely including 13 (12.4%) in the low CCI group and 4 (13.3%) in the high CCI group (p=1.00). There was no significant difference in OS between the low- and high-CCI groups (5-year OS 70.3% vs 68.7%, p=0.9; See Figure 2). Within the cohort of patients treated with intensive induction therapy, there was no significant impact of CCI on incidence of unplanned hospitalizations, de-escalation or discontinuation of therapy, or OS (p> 0.3).
Conclusion
CCI score was not shown to be a reliable predictor of unplanned hospitalizations, premature cessation of chemotherapy, or OS in our cohort, although many of our patients had very limited comorbidities. These results suggest that patients with limited comorbid conditions can likely be successfully managed with appropriate supportive care and should be considered for the most effective regimens. Future studies with a larger patient population with increased number of comorbidities may improve our ability to detect the impact of CCI on these outcomes and explore the relative contribution of specific comorbidities in MCL.

Disclosures
Calzada: Seattle Genetics: Research Funding. Flowers:BeiGene: Research Funding; Burroughs Wellcome Fund: Research Funding; Abbvie: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics/ Janssen: Consultancy; Millennium/Takeda: Research Funding; Gilead: Consultancy; Genentech/Roche: Consultancy; Janssen Pharmaceutical: Research Funding; Genentech/Roche: Research Funding; OptumRx: Consultancy; Acerta: Research Funding; Gilead: Research Funding; Denovo Biopharma: Consultancy; Celgene: Research Funding; Bayer: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; National Cancer Institute: Research Funding; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Pharmacyclics: Research Funding; V Foundation: Research Funding. Cohen:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Takeda: Research Funding; BioInvent: Consultancy; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.