Impact of Rituximab in the Clinical Outcomes of Hairy Cell Leukemia: A Single-Institution Analysis

Background: Hairy cell leukemia (HCL) is an indolent mature B-cell disorder that comprises ~2% of all leukemias. Purine analoguess (PNAs) such as cladribine (2-CdA) remains as the standard initial treatment with high response rate, but frequent late relapses occur. The addition of rituximab (R) has shown efficacy as a single agent and in combination in the first- and second-line settings. In this single-institution study, we show the impact of rituximab (R) in the outcomes of HCL.

Methods: An IRB-approved retrospective analysis was performed using patients diagnosed with HCL or HCL-variant (HCLv) who were seen at Moffitt Cancer Center between January 2000 and February 2018. Clinical and pathologic data at diagnosis as well as treatment history and clinical outcome data were collected. Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints included overall response rate (ORR) defined as complete response + partial response (CR + PR). Statistical comparisons and survival analyses were performed using SPSS^TM Statistics and GraphPad Prism^TM.

Results: We identified 136 patients but 104 cases had available treatment data and follow up (96 HCL, 8 HCLv). The median follow-up was 79 months. The median age was 57 years (27 - 89) with a male:female ratio of 3.7:1 . Regarding symptoms present at diagnosis, most patients presented with cytopenias and splenomegaly (70% and 34%, respectively), with weight loss and recurrent infections present in 11% and 13%, respectively. The 5 and 10 year OS was 97% and 91%, respectively, with 2 deaths reported secondary to HCL. The median PFS for all patients receiving first-line therapy was 93 months. Several clinical and pathologic factors present at diagnosis were independently associated with worse PFS, including recurrent infections (HR 3.11, p = 0.01), weight loss (HR 2.67, p = 0.019), diagnosis of HCL-v (HR 3.22, p = 0.015), Hgb < 12 gm/dL (HR 2.41, p = 0.054), and abnormal cytogenetics (HR 13.6, p = 0.01). There were 18 patients in the treated population with known BRAF mutation status (11 positive, 7 negative) which did not correlate with PFS. Patients who achieved a CR after 1^st line therapy had significantly longer PFS compared to those who achieved a PR (median PFS 103 vs 39 months, p = 0.001). Most patients received 2-CdA or 2-CdA+R (79 and 13, respectively) as first line with a higher CR rate in the 2-CdA+R group (100% vs 73%) and a higher median PFS for [not reached (NR) and 82 months, respectively, p= 0.09] with only 1 relapse in the 2-CdA+R group. In the 2^nd line setting, 2-CdA+R (n=9) was also associated with a higher CR rate than 2-CdA alone (n=15, 89% vs 80%) with only 1 relapse in the 2-CdA+R group at 97 months. The median PFS for 2^nd line 2-CdA+R vs 2-CdA was 97 and 43 months, respectively (p=0.31).

Conclusions: In this study, we report a large, single-institution dataset of HCL and HCLv patients with long-term follow-up. The addition of rituximab improved the PFS in patients with HCL in the first-line and relapse settings and should be considered as a reasonable addition in the therapy for HCL even in the absence of randomized trials.