Effects of chronic lymphocytic leukaemia ( CLL) ‐directed therapy on diffuse large B‐cell lymphoma ( DLBCL) type Richter transformation compared to de novo DLBCL in a nationwide cohort

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Abstract
Summary: Diffuse large B‐cell lymphoma (DLBCL) type Richter transformation (DLBCL‐RT) in patients with chronic lymphocytic leukaemia (CLL) has a worse prognosis compared to de novo DLBCL (dnDLBCL). We investigated outcomes of patients with DLBCL‐RT with or without previous CLL‐directed therapy compared to dnDLBCL between 2002 and 2022. We included 6525 patients with dnDLBCL and 383 patients with DLBCL‐RT, of whom 260 had Richter transformed treatment‐naïve CLL (RT:TN‐CLL) and 123 had Richter transformed treatment exposed CLL (RT:TE‐CLL). Median time to next treatment or death (TTNTd) was 4.83 years, 1.43 years and 0.46 years for patients with dnDLBCL, RT:TN‐CLL and RT:TE‐CLL respectively. Median overall survival (OS) following first‐line treatment was 9.42, 5.22 and 0.72 years for dnDLBCL, RT:TN‐CLL and RT:TE‐CLL respectively ( p < 0.001). In a high‐validity subcohort, OS did not differ significantly between RT:TN‐CLL and dnDLBCL (median OS 9.85 years [CI: 9.16–10.70] for dnDLBCL, 6.07 years [CI: 4.23–not estimable] for RT:TN‐CLL and 1.15 years [CI: 0.76–3.66] for RT:TE‐CLL). In conclusion, patients with RT:TE‐CLL had inferior TTNTd and OS compared to RT:TN‐CLL and dnDLBCL. RT:TN‐CLL demonstrated inferior TTNTd compared to dnDLBCL, but OS approached that of dnDLBCL. This indicates that for patients with RT:TN‐CLL, chemoimmunotherapy may still be an effective modality, while patients with RT:TE‐CLL need novel treatment options.
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  • Genmab

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