Demographics By Age Group (AG) and Line of Therapy (LOT) in Chronic Lymphocytic Leukemia (CLL) Patients (Pts) Treated in US Practices from the Connect^® CLL Registry

Introduction:CLL pts who qualify for participation in clinical trials are often thought of as a highly selected population. Therefore whether safety and efficacy data from these trials can be generalized to all CLL pts treated in the community setting is unknown. Prospective, observational studies can provide significant insight into pt and disease characteristics as well as practice patterns in different clinical settings. Here we report on baseline demographics and clinical characteristics for 1495 pts who participated in the Connect CLL observational study and were followed prospectively.

Methods: Connect^®CLL is a non study-specific intervention treatment registry which collects data on the management and outcomes of CLL pts in clinical, academic and community practices in the US. Clinical information was prospectively collected for pts treated in community (n=1312), academic (n=155), or government (n=28) centers in the US between March 2010 – Jan 2014. Pts eligible for treatment or on treatment not more than 2 months were eligible for enrollment. Here we report on the baseline demographics and clinical characteristics of a large CLL cohort stratified by AG, LOT and type of treatment center.

Results:In total,1,495 pts were accrued with a median age at enrollment of 69 (range 22–99). Pts were Caucasian (92.2%), African American (6.9%), and male (63.7%). Median duration from diagnosis until initial therapy was 3.7 years (range 0-32). Age of enrolled pts was as follows; 527 pts age <65 years (AG1; 35%); 511 age 65–75 (AG2; 34%); and 457 age ≥75 (AG3; 31%) at the time of enrollment. Eight hundred and ninety-four pts (60%) were treated with front-line therapy (LOT1); 259 pts (17%) treated with second-line therapy (LOT2); and 342 pts (23%) treated beyond second-line therapy (LOT≥3). Patient age: Pt age was associated with significant variation in several clinical variables: Charlson comorbidity index (CCI) score ≥3 (AG 1-3 35/46/52%; p<0.0001), ECOG PS = 0 (AG1-3 60, 48, 33%, p<0.0001) and mean creatinine clearance (CrCl) decreased (AG 1-3 101/74/53 mL/min; p<0.0001). Line of therapy: Differences in baseline characteristics were observed between pts enrolled at LOT1 (previously untreated) and LOT2/≥3 (relapsed). Median age of pts accrued at LOT1 was 68 vs. 70 years for pts enrolled at LOT2/≥3 (p=0.007). ECOG PS = 0 was more frequent at LOT1 (50%) vs. LOT2/≥3 (42%) (p=0.0057). CCI ≥3 at LOT1 was 41% vs 48% at LOT2/≥3 (p=0.0072). When adjusted for differences in age, logistic regression also demonstrated significant differences in performance status (PS=0; p=0.02) and CCI (p=0.03) stratified by LOT. Treating institution: Baseline characteristics also differed by type of treating institution. Median age was 63 vs 70 at academic vs non-academic (p<0.0001). Pts treated at academic sites also had lower CCI (CCI≤2; 72.9% vs 54.2%, academic vs non-academic) and higher median CrCl (86.4 vs 71.4) (p=0.0017). In this registry, only 16% of patients under age 75 had CCI <= 2, CrCl >= 70 mL/min, ECOG 0-1; 18% of patients on LOT1 and 12% of pts on LOT=2 would satisfy these criteria. They represent 36% of eligible pts from academic treating institutions and 13% from community/government centers. Only 20% of patients on LOT1 would satisfy enrollment criteria for CLL8 (FCR vs. FC; Hallek; Lancet 2010) CLL 10 (BR vs FCR; NCT00769522). which did not have enrollment restrictions for age.

Conclusions:Baseline characteristics of pts with CLL vary by age, LOT, and type of treatment center. In this large prospective observational study, our data confirms that older pts typically have a worse ECOG PS, more medical comorbidities, more advanced disease when initiating therapy and a lower probability of being treated at an academic medical center. Based on inclusion criteria used for entry in either CLL10 or CLL8, fewer than 20% of pts satisfy age, renal clearance, and fitness profile to be considered suitable for aggressive chemoimmunotherapy in the front line setting. This observation supports the notion that current clinical trial data might not always be applicable to the general CLL population seen in the community and argues for designing clinical trials that are more generalizable to the broader pt population.