Evaluating the effectiveness and tolerability of chemotherapy in hairy cell leukemia: A comprehensive systematic review and meta-analysis.

person Jawad Basit Rawalpindi Medical University, Rawalpindi, Pakistan info_outline Jawad Basit, Zaofashan Zaheer, Aleena Ahmed, Maurish Fatima, Usman Ali Akbar, Nithya Ramesh, Asna Shahab, Mohammad Ebad Ur Rehman, Zunairah Shah, Sajeel Saeed, Mahboob Ahmad, Azka Aisha

Authors person Jawad Basit Rawalpindi Medical University, Rawalpindi, Pakistan info_outline Jawad Basit, Zaofashan Zaheer, Aleena Ahmed, Maurish Fatima, Usman Ali Akbar, Nithya Ramesh, Asna Shahab, Mohammad Ebad Ur Rehman, Zunairah Shah, Sajeel Saeed, Mahboob Ahmad, Azka Aisha Organizations Rawalpindi Medical University, Rawalpindi, Pakistan, King Edward Medical University, Lahore, Pakistan, King Edward Medical University Pakistan, Jhelum, Pakistan, North Shore University Hospital, Manhasset, NY, Mercy Catholic Medical Center, Lansdowne, PA, Conemaugh Memorial Medical Center, Johnstown, PA, Louis A Weiss Memorial Hospital, Chicago, IL, 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. Many treatment options are available for HCL. Our study aims to elucidate the safety and efficacy of each intervention through the pooled proportion of response to treatment and adverse events. Methods: We conducted a literature search across PubMed, Embase, Cochrane, and Google Scholar from inception till February 2023. We included clinical trials and cohorts of patients with HCL receiving modern anticancer drugs (cladribine, rituximab, cladribine plus rituximab, BRAF inhibitors, anti-CD22 monoclonal antibodies, and ibrutinib). The primary efficacy outcomes were Objective Response Rate (ORR) and Complete Response Rate (CRR) and the primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random Effects Model, with subgroup analysis for HCL type and study design. Results: Our meta-analysis included 44 studies (28 trials and 16 cohorts) with 3976 patients with HCL. The median age was 56.7 years. The highest efficacy was seen in patients receiving combination therapy of cladribine and rituximab, with an ORR of 97% and CRR of 92%. Cladribine monotherapy showed an ORR of 95% and CRR of 79%, while rituximab monotherapy had an ORR of 62% and CRR of 31%. BRAF inhibitors, anti-CD22 monoclonal antibodies, and ibrutinib showed less efficacy, with ORRs of 92%,78% and 51% and CRRs of 41%, 49%, and 17% respectively. Subgroup analysis for study design and HCL type did not resolve heterogeneity. The ORR and CRR with 95% Confidence Intervals and AEs for each regimen are given in the table. Conclusions: Cladribine with rituximab is the most effective treatment for untreated and relapsed HCL patients, with neutropenia as the most common AE. Since we pooled the proportions for treatment-naïve and relapsed cases together due to inavailability of segregated data, the results should be used cautiously in clinical decision making and limit the derivation of consensus for treatment of newly diagnosed or relapsed HCL. Cladribine n = 2806 Rituximab n = 64 Combination Therapy:Cladribine and Rituximab n = 149 BRAF inhibitors n = 196 Anti-CD22 Monoclonal Antibodies n = 260 Ibrutinib n = 65 Number of studies 22 10 trials, 12 cohorts 3 trials 5 3 trials, 2 cohorts 7 trials 5 3 trials, 2 cohorts 2 trials Median Age (years) 53.9 56 56.8 61.6 57.7 64.5 ORR (95%C.I) 95% (0.91, 0.98) 62%(0.26,0.98) 97%(0.92, 1.0) 92&(0.88,1.0) 77%(0.71,0.84) 51%(0.39,0.63) CRR(95% C.I) 79% (0.73, 0.84) 31%(0.08,0.54) 92%(0.83,1.0) 41%(0.32, 0.495) 49%(0.40,0.59) 17%(0.08,0.26) Neutropenia n = 150/213,72.3%* NR n = 25/90,23.6%* NR n = 6/160,3.3%* n = 13/65,19.9%* Lymphocytopenia NR NR n = 34/90(39.3%,p = 0.06) NR n = 22/160,13.3%* n = 13/65,19.9%* Infections Grade≥3 n = 146/811,14.6%* NR n = 13/70(17.3%,p = 0.25) NR NR n = 19/65,28.9%*