Table 1.

Time points and genetic characteristics of patients with CLL and disease progression

Patient-identifying codeTime point∗ Sample IDDrugDays from DxWBC countAbsolute lymphocyte countBTK mutations, CCF (%) (whole-exome sequencing)BTK mutations, VAF (%) (RNA)
CLL Pt 6  CLL Pt 6 #1 Pretreatment 97 139.6 Not available No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #2 After BR+L, before Acala 868 181.45 163.31 No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #3 Acala 1184 64.46 59.95 No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #4 Acala 1533 19.48 14.81 No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #5 Acala 1878 21.42 16.06 p.C481S, 16 p.C481S, 8 
  CLL Pt 6 #6 Acala 2037 20.14 13.89 p.C481S, 47; p.T474I, 3 p.C481S, 64; p.T474I, 2 
  CLL Pt 6 #7 Acala 2212 51.4 40.61 p.C481S, 92; p.T474I, 4  
  CLL Pt 6 #8 Veca 2261 102.61 96.46 p.C481S, 100; p.T474I, 9 p.C481S, 93; p.T474I, 3 
  CLL Pt 6 #9 Veca 2345 237.38 227.88 p.C481S, 93; p.T474I, 3 p.C481S, 91; p.T474I, 2 
  CLL Pt 6 #10 Veca 2429 356.2 338.39 p.C481S, 97; p.T474I, 2 p.C481S, 91; p.T474I, 2 
  CLL Pt 6 #11 Veca 2492 359.32 341.36 p.C481S, 97; p.T474I, 3 p.C481S, 86; p.T474I, 6 
 D 0 CLL Pt 6 #12 Pirto 2599 363.47 341.66 p.C481S, 95; p.T474I, 5 p.C481S, 87; p.T474I, 7 
 3 mo CLL Pt 6 #13 Pirto 2681 148.37 139.47 p.C481S, 69; p.T474I, 24 p.C481S, 40; p.T474I, 32 
 6 mo CLL Pt 6 #14 Pirto 2765 74.81 65.08 p.C481S, 31; p.T474I, 62; p.T474L, 3 p.C481S, 12; p.T474I, 71; p.T474L, 2 
 9 mo CLL Pt 6 #15 Pirto 2856 61.58 54.81 p.C481S, 6; p.T474I, 89; p.T474L, 4; p.M477I, 2 p.C481S, <1; p.T474I, 85; p.T474L, 6 
 12 mo CLL Pt 6 #16 Pirto 2941 105.72 97.26 p.C481S, 2; p.T474I, 99; p.T474L, 5; p.M477I, 2 p.C481S, <1; p.T474I, 87; p.T474L, 8 
CLL Pt 7  CLL Pt 7 #1 After FCR 2109 9.5 4.93 No BTK mutation detected  
  CLL Pt 7 #2 Ibr 3266 4.48 2.52 No BTK mutation detected  
  CLL Pt 7 #3 Ibr 4484 21.32 17.51 p.C481S, 6; p.C481R, 33 p.C481S, 7; p.C481R, 18 
  CLL Pt 7 #4 Ibr after progression 4532 70.97 38.32 p.C481S, 11; p.C481R, 34 p.C481S, 14; p.C481R, 40 
  CLL Pt 7 #5 KTE-X19 CAR-T therapy 4800 12.86 8.33 p.C481S, 16; p.C481R, 31; p.L528W, 1 p.C481S, 25; p.C481R, 24; p.L528W, 2 
  CLL Pt 7 #6 KTE-X19 CAR-T 4813 27.53 23.18 p.C481S, 4; p.C481R, 29; p.L528W, 1 p.C481S, 21; p.C481R, 27; p.L528W, 2 
 D 0 CLL Pt 7 #7 Pirto 4918 26.71 21.9 p.C481S, 18; p.C481R, 25; p.L528W, 2 p.C481S, 23; p.C481R, 51 
 3 mo CLL Pt 7 #8 Pirto 5009 54.04 50.69 p.C481S, 37; p.C481R, 28; p.L528W, 4 p.C481S, 22; p.C481R, 11; p.L528W, 43 
 5.8 mo CLL Pt 7 #9 Pirto 5094 27.2 19.72 p.C481S, 41; p.C481R, 22; p.L528W, 7 p.C481S, 7; p.C481R, 5; p.L528W, 82 
 8 mo CLL Pt 7 #10 Pirto after progression 5161 30.85 26.99 p.C481S, 28; p.C481R, 20; p.L528W, 30 p.C481S, 5; p.C481R, 2; p.L528W, 91 
Patient-identifying codeTime point∗ Sample IDDrugDays from DxWBC countAbsolute lymphocyte countBTK mutations, CCF (%) (whole-exome sequencing)BTK mutations, VAF (%) (RNA)
CLL Pt 6  CLL Pt 6 #1 Pretreatment 97 139.6 Not available No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #2 After BR+L, before Acala 868 181.45 163.31 No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #3 Acala 1184 64.46 59.95 No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #4 Acala 1533 19.48 14.81 No BTK mutation detected No BTK mutation detected 
  CLL Pt 6 #5 Acala 1878 21.42 16.06 p.C481S, 16 p.C481S, 8 
  CLL Pt 6 #6 Acala 2037 20.14 13.89 p.C481S, 47; p.T474I, 3 p.C481S, 64; p.T474I, 2 
  CLL Pt 6 #7 Acala 2212 51.4 40.61 p.C481S, 92; p.T474I, 4  
  CLL Pt 6 #8 Veca 2261 102.61 96.46 p.C481S, 100; p.T474I, 9 p.C481S, 93; p.T474I, 3 
  CLL Pt 6 #9 Veca 2345 237.38 227.88 p.C481S, 93; p.T474I, 3 p.C481S, 91; p.T474I, 2 
  CLL Pt 6 #10 Veca 2429 356.2 338.39 p.C481S, 97; p.T474I, 2 p.C481S, 91; p.T474I, 2 
  CLL Pt 6 #11 Veca 2492 359.32 341.36 p.C481S, 97; p.T474I, 3 p.C481S, 86; p.T474I, 6 
 D 0 CLL Pt 6 #12 Pirto 2599 363.47 341.66 p.C481S, 95; p.T474I, 5 p.C481S, 87; p.T474I, 7 
 3 mo CLL Pt 6 #13 Pirto 2681 148.37 139.47 p.C481S, 69; p.T474I, 24 p.C481S, 40; p.T474I, 32 
 6 mo CLL Pt 6 #14 Pirto 2765 74.81 65.08 p.C481S, 31; p.T474I, 62; p.T474L, 3 p.C481S, 12; p.T474I, 71; p.T474L, 2 
 9 mo CLL Pt 6 #15 Pirto 2856 61.58 54.81 p.C481S, 6; p.T474I, 89; p.T474L, 4; p.M477I, 2 p.C481S, <1; p.T474I, 85; p.T474L, 6 
 12 mo CLL Pt 6 #16 Pirto 2941 105.72 97.26 p.C481S, 2; p.T474I, 99; p.T474L, 5; p.M477I, 2 p.C481S, <1; p.T474I, 87; p.T474L, 8 
CLL Pt 7  CLL Pt 7 #1 After FCR 2109 9.5 4.93 No BTK mutation detected  
  CLL Pt 7 #2 Ibr 3266 4.48 2.52 No BTK mutation detected  
  CLL Pt 7 #3 Ibr 4484 21.32 17.51 p.C481S, 6; p.C481R, 33 p.C481S, 7; p.C481R, 18 
  CLL Pt 7 #4 Ibr after progression 4532 70.97 38.32 p.C481S, 11; p.C481R, 34 p.C481S, 14; p.C481R, 40 
  CLL Pt 7 #5 KTE-X19 CAR-T therapy 4800 12.86 8.33 p.C481S, 16; p.C481R, 31; p.L528W, 1 p.C481S, 25; p.C481R, 24; p.L528W, 2 
  CLL Pt 7 #6 KTE-X19 CAR-T 4813 27.53 23.18 p.C481S, 4; p.C481R, 29; p.L528W, 1 p.C481S, 21; p.C481R, 27; p.L528W, 2 
 D 0 CLL Pt 7 #7 Pirto 4918 26.71 21.9 p.C481S, 18; p.C481R, 25; p.L528W, 2 p.C481S, 23; p.C481R, 51 
 3 mo CLL Pt 7 #8 Pirto 5009 54.04 50.69 p.C481S, 37; p.C481R, 28; p.L528W, 4 p.C481S, 22; p.C481R, 11; p.L528W, 43 
 5.8 mo CLL Pt 7 #9 Pirto 5094 27.2 19.72 p.C481S, 41; p.C481R, 22; p.L528W, 7 p.C481S, 7; p.C481R, 5; p.L528W, 82 
 8 mo CLL Pt 7 #10 Pirto after progression 5161 30.85 26.99 p.C481S, 28; p.C481R, 20; p.L528W, 30 p.C481S, 5; p.C481R, 2; p.L528W, 91 

p.C481S (c.1442G>C); p.C481R (c.1441T>C).

p.T474I (c.1421C>T); p.T474L (two nucleotide changes c.1420A>C; c.1421C>T).

p.M477I (c.1431G>C).

p.L528W (c.1583T>G).

BR + L, bendamustine, rituximab, and lenalidomide; KTE-X19 CAR-T, experimental anti-CD19 chimeric antigen receptor T-cell therapy (Kite); FCR, fludarabine, cyclophosphamide, and rituximab; Veca, vecabrutinib.

∗

Time point indicates the sample time points (months after pirtobrutinib treatment), which correspond to those used in Figure 4.

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