Relative efficacy of systemic treatments for patients with relapsed/refractory chronic lymphocytic leukemia: a network meta‑analysis according to 17p deletion/TP53 mutations
	    		
		   		
		   			
		   		
	    	
    	 
    	10.1007/s44313-024-00038-2
   		
        
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Jinchul  KIM
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Jinhyun  CHO
			        		
			        		;
		        		
		        		
		        		
			        		Joo Han  LIM
			        		
			        		;
		        		
		        		
		        		
			        		Moon Hee  LEE
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Department of Hematology‑Oncology, Inha University College of Medicine and Hospital, 7‑206 Third Street, Shinheung‑Dong Jung‑Gu, Incheon, Republic of Korea
			        		
		        		
	        		
        		 
        	
        	
        	
        		- Publication Type:RESEARCH
 
        	
        	
            
            
            	- From:Blood Research
	            		
	            		 2025;60():1-
	            	
            	
 
            
            
            	- CountryRepublic of Korea
 
            
            
            	- Language:English
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	 Purpose:This network meta-analysis aimed to evaluate the relative efficacy of systemic treatments in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), focusing on key genetic mutations, specifically the 17p deletion and TP53 mutations. 
				        	
				        
				        	Methods:We conducted a systematic literature review to identify all publicly available randomized controlled trials (RCTs) using PubMed, EMBASE, the Cochrane database, and meeting abstracts published through December 2023.A Bayesian network meta-analysis was performed to estimate the hazard ratios (HRs) for progression-free survival (PFS) with 95% confidence intervals (CIs) and to determine the ranking of the included regimens. 
				        	
				        
				        	Results:Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis. Venetoclax plus rituximab and zanubrutinib emerged as the most effective treatments for the overall R/R CLL population, showing the lowest PFS HR (HR 0.62, 95% CI 0.32–1.20 and HR 0.65, 95% CI 0.49–0.86, respectively) versus ibrutinib, and were ranked as the best agent (surface under the cumulative ranking curve [SUCRA] value of both 90%, respectively) among the included drugs. In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31–0.88 versus ibrutinib) with the highest SUCRA value (97%). In patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI 0.26–0.94 versus ibrutinib) with a SUCRA value of 94%. 
				        	
				        
				        	Conclusion:Our findings highlight the superior efficacy of venetoclax plus rituximab and zanubrutinib for treating R/R CLL and confirm that the role of each regimen may vary depending on the clinically significant mutations.