Characteristics and therapies for pure red cell aplasia in patients with chronic lymphocytic leukemia (CLL) - a real world analysis from trinetx database

Abstract INTRODUCTION Pure red cell aplasia (PRCA) is characterized by normochromic normocytic anemia, reticulocytopenia, and reduction or absence of erythroid precursors in the bone marrow. Secondary acquired PRCA associated with lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) is a rare disorder with an estimated prevalence of less than 1%. Limited information is known about the treatment and outcomes of PRCA in CLL. PCRA in CLL is usually treated with corticosteroids, immunosuppressive agents such as cyclosporine or cyclophosphamide. CD20 directed monoclonal antibodies such as rituximab and Bruton Tyrosine Kinase inhibitors (BTKi) are also being used. The aim of this study is to identify characteristics of the CLL patients with PRCA and explore treatments used in the real-world settings. METHODS Using TriNteX database, we performed a retrospective analysis of patients with a diagnosis of CLL with PRCA. Data for this analysis was obtained from electronic medical records across the network of 153 large healthcare organizations called Global Collaborative Network. Baseline patient characteristics including lab values were included within 7 days of index event. Treatment pathways and sunburst diagrams were used to evaluate the distribution of treatment regimens across all lines of treatment. Kaplan-Meier curve was used to calculate overall survival. RESULTS Out of 194,996 patients with CLL/SLL identified, 435 patients had a diagnosis of PRCA. Baseline characteristics were available for 401 patients. Most of the patients were male (n=239, 61%) and White (n=286, 73%). The median age at diagnosis was 66.2 years. Mean hemoglobin 9.32 ± 2.58 gm/dL whereas mean hematocrit was 27.8 ± 7.84. Mean Leukocyte count was 16.9 ± 46.4 × 103/uL. Mean reticulocyte count was 1.11% ± 1.21. Out of 401, treatment pathways were available for 307 patients. Corticosteroids as single agent was the most used first line (1L) treatment in 214 (69.7%) patients followed by cyclophosphamide in 23 (7.5%) and ibrutinib in 15 (4.9%) patients. Steroids were given in combination with rituximab in 9 (2.9%) and with cyclosporine in 15 (4.9%) patients in 1L. Five (1.6%) patients received single agent rituximab while 6 (2%) were given cyclophosphamide in 1L. Other less commonly used treatments in 1L were acalabrutinib in 1.6%, venetoclax in 0.6%, obinutuzumab in 0.6%, and steroids + venetoclax in 0.6% patients. The longest median time on treatment (mToT) was seen in patients receiving steroids + cyclosporine with mToT of 194 days followed by ibrutinib 101 days. Both corticosteroids alone and cyclosporine alone were used for a median of 85 days whereas steroids + rituximab had mToT of 30 days. Across six lines of therapies, corticosteroids were the most used agent in 264 instances followed by cyclosporine in 59 instances (19 in 2L, 22 in 3L, 9 in 4L, 14 in 5L, 9 in 6L). Steroids in combination with rituximab were used 37 times (14 in 2L, 6 in 3L, 8 in 4L, 1 in 5L, 4 in 6L) whereas ibrutinib had 35 instances. Corticosteroids in combination with cyclosporine was the 5th most used regimen with 32 instances. With median follow up was 27.2 months, the overall survival in patients with PRCA associated with CLL is 81.2 months. CONCLUSION Pure red cell aplasia in patients with CLL is a rare phenomenon. Corticosteroids alone or in combination with immunosuppressive agents or B-cell targeting drugs are commonly used in the first line settings. Collaborative efforts across institutions are needed to study the use of newer therapies for this indication.