Learning points

• Diagnosis of CLL: clonal B cell population >5 x 10⁹/L with typical phenotype (CD5+ CD23+, 19+, 20+ FMC7-, weak/- CD79b)
• <5 x 19⁹/L lymphocytes but same clonal phenotype = Monoclonal B cell Lymphocytosis (MBL)
• LN or extramedullary involvement but <5 x 10⁹/L lymphocytes = Small Lymphocytic Leukaemia (SLL)
• Early stage CLL (A) or asymptomatic – currently  observation management but important to counsel patients on infection risk. “ watch, wait and vaccinate” – Check immunoglobulins and deliver Prevenar13, followed at least 2 months later by Pneumovax23. Also advise on annual ‘flu vaccine. No live vaccines including live shingles vaccine to be given (Nb. new recombinant vaccine will be available soon). Check functional antibody responses after pneumococcal vaccination
• Indications for treating: As per IWCLL guidance : Bulky lymph nodes, B symptoms, Rising WCC (LDT <6 months or 50% increase in 2 months), Hb <100, plt <100 BUT important to do BMAT as prognosis is different if its immune versus CLL infiltrate(Moreno et al Blood 2010)
• Check TP53/17p deletion prior to treating and weigh up comorbidities/fitness
• TP53/17p naïve patients Current First Line in UK:
  • in UK if young and fit – currently FCR. Long remissions and MRD negativity seen with FCR in IGHV mutated patients – advisable to check this status before treating if available.
  • Fit but older – BR.
  • More frail – chlorambucil and obinutuzumab (MRD still seen in 20%). Ibrutinib is licensed too (resonate study) but not available first line in UK currently.
• TP53 mutated/17p deleted first line In UK:
  • Ibrutinib or idelalisib plus rituximab if ibrutinib contraindicated (must CMV monitor). Venetoclax also licensed but not currently available via NICE
• MRD negative in CLL = <1 in 10,000 lymphocytes have B-CLL phenotype – flow or PCR. Most powerful predictor of PFS and OS.
• Relapsed patients in UK
  • venetoclax + rituximab (as per Murano trial: fixed 2 year duration. >60% obtained MRD negativity) or ibrutinib or idelalisib + rituximab