Table 3.

Algorithm for frontline treatment in CLL

Clinical stage of diseaseDel(17p) and/or TP53 mutationPhysical fitnessRecommendation for frontline treatment
Asymptomatic Binet A-B or Rai 0-II Irrelevant Irrelevant Watch and wait until symptomatic 
SymptomaticBinet C or Rai III-IV* Not present Fit FCR; → Consider BR, if >65 y 
Unfit Chlorambucil + obinutuzumab or chlorambucil + ofatumumab or ibrutinib 
Present Irrelevant Ibrutinib → Consider venetoclax or idelalisib + rituximab if unsuitable for ibrutinib 
 Frail (no-go) Irrelevant Best supportive care 
Clinical stage of diseaseDel(17p) and/or TP53 mutationPhysical fitnessRecommendation for frontline treatment
Asymptomatic Binet A-B or Rai 0-II Irrelevant Irrelevant Watch and wait until symptomatic 
SymptomaticBinet C or Rai III-IV* Not present Fit FCR; → Consider BR, if >65 y 
Unfit Chlorambucil + obinutuzumab or chlorambucil + ofatumumab or ibrutinib 
Present Irrelevant Ibrutinib → Consider venetoclax or idelalisib + rituximab if unsuitable for ibrutinib 
 Frail (no-go) Irrelevant Best supportive care 

BR, bendamustine and rituximab; FCR, fludarabine, cyclophosphamide and rituximab.

*

In general, clinical trials should be offered, if available.

Other purine analogs-based chemoimmunotherapy, according to national guidelines.

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