Outcomes of intravenous and subcutaneous cladribine administration in patients with hairy cell leukemia: A systematic review and meta-analysis.

person Jawad Basit Rawalpindi Medical University, Rawalpindi, Pakistan info_outline Jawad Basit, Zaofashan Zaheer, Muhammad Hammad Khan, Maurish Fatima, Sobaan Taj, Usman Ali Akbar, Mohammad Ebad Ur Rehman, Sajeel Saeed, Sindhu Vikash, Nithya Ramesh, Asna Shahab, Muhammad Shahid, Aqsa Komel, Umer Irshad, Shehroze Tabassum, Aroma Naeem

Authors person Jawad Basit Rawalpindi Medical University, Rawalpindi, Pakistan info_outline Jawad Basit, Zaofashan Zaheer, Muhammad Hammad Khan, Maurish Fatima, Sobaan Taj, Usman Ali Akbar, Mohammad Ebad Ur Rehman, Sajeel Saeed, Sindhu Vikash, Nithya Ramesh, Asna Shahab, Muhammad Shahid, Aqsa Komel, Umer Irshad, Shehroze Tabassum, Aroma Naeem Organizations Rawalpindi Medical University, Rawalpindi, Pakistan, King Edward Medical University, Lahore, Pakistan, King Edward Medical University Pakistan, Jhelum, Pakistan, Hackensack-Meridian Jersey Shore University Medical Center, Neptune, NJ, North Shore University Hospital, Manhasset, NY, Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, NY, Mercy Catholic Medical Center, Lansdowne, PA, Conemaugh Memorial Medical Center, Johnstown, PA, Nishtar Medical University, Multan, Multan, Pakistan, Nishtar Medical University Multan, Multan, Pakistan Abstract Disclosures Research Funding No funding received None. Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Cladribine (2CdA) monotherapy is used as a first line treatment for HCL. 2CdA can be administered intravenously (IV) or subcutaneously (SC). The aim of our study is to compare the safety and efficacy of these two routes of administration of 2CdA as a first line treatment of HCL. Methods: We conducted a systematic literature search across multiple databases and Google up to February 2023. We included studies that reported outcomes for either intravenous (IV) or subcutaneous (SC) cladribine (2CdA) therapy, as well as those that directly compared the two routes. Our primary efficacy outcomes were overall response rate (ORR) and complete response rate (CRR), and our primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random effects model and conducted subgroup analysis for HCL type (classical vs classic and variant both). We calculated odds ratios (ORs) for studies involving a head-to-head comparison between the two routes and used the Higgins I2 statistic to assess heterogeneity. Results: We identified a total of 25 studies (15 trials, 10 cohorts) with a patient population of 2669. The median age of the patients was 53.5 years. The pooled ORR and CRR for IV and SC 2CdA therapy were 96%, 82%, 88% and 67% respectively. The incidence of neutropenia (82% vs 61%) and infections (13% vs 16%) was greater for SC 2CdA than IV 2CdA. Five studies provided a direct comparison between SC and IV routes but three were excluded from the analysis due to unavailability of desired outcomes. Studies involving a direct comparison between the 2 routes of administration showed that the odds of achieving CRR were 86.6% greater with IV than SC 2CdA but these results were not significant. The proportion of adverse events was comparable for IV and SC routes. Subgroup analysis for HCL type did not resolve heterogeneity for ORR and CRR. It did, however, result in greater ORR for classic (92%) and mixed (92%) HCL treated with SC 2CdA. Conclusions: Compared to SC 2CdA, IV 2CdA is safer and more effective as a first-line treatment of HCL. However, future high-power randomized control trials that directly compare IV and SC routes are needed to confirm this evidence. ORR 96%(0.94,0.99) 88%(0.79,0.97) NA CRR 82%(0.75,0.89) 67%(0.51,0.79) OR: 1.866(0.157,22.145),p = 0.621 Fever 19%(-0.14,0.52),p = 0.257 NR OR:1.196(0.335,4.270),p = 0.783 Neutropenia 61%(0.43,0.78)* 82%(0.65,0.98) * OR 0.294(0.076,0.137),p = 0.076 Infection 13%(0.02,0.23),p = 0.018 16%(0.11,0.22) * NA OR:Odds Ratio, NR: Not Reported, NA: Not Applicable *p < 0.001.