Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation

Oscier, David; Wade, Rachel; Davis, Zadie; Morilla, Alison; Best, O. Giles; Richards, Sue; Else, Monica; Matutes, Estella; Catovsky, Daniel

doi:10.3324/haematol.2010.025338

Cited by 115 publications

(114 citation statements)

References 33 publications

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“…Thus the percentages shown here do not correspond to those shown in Fig 2A, which include these 44 patients censored at the date of last known contact.bPoor risk – known TP53 deletion >10%; intermediate risk – without TP53 deletion (≤10%) and with at least one of: unmutated IGHV genes and/or IGHV3‐21 usage, 11q deletion, β‐2 microglobulin ≥4 mg/l; good risk – none of the above and mutated IGHV genes (Oscier et al , 2010). …”

Section: Resultsmentioning

confidence: 98%

“…Poor risk – known TP53 deletion >10%; intermediate risk – without TP53 deletion (≤10%) and with at least one of: unmutated IGHV genes and/or IGHV3‐21 usage, 11q deletion, β‐2 microglobulin ≥4 mg/l; good risk – none of the above and mutated IGHV genes (Oscier et al , 2010). …”

Section: Resultsmentioning

confidence: 99%

“…The patients were previously untreated, 191 (25%) having Binet stage A‐progressive disease, 352 (45%) stage B and 234 (30%) stage C. The male:female ratio was 3:1 and the median age was 65 years (range 35–86 years). Biological, cytogenetic and molecular markers were available and have been reported elsewhere, together with a description of the cut‐offs used to define positivity (Oscier et al , 2010, 2013). These markers were available at randomization only, not at relapse.…”

Section: Methodsmentioning

confidence: 99%

“…These markers were available at randomization only, not at relapse. Risk groups, which were evenly distributed across the three randomised arms, were initially identified as follows: poor risk – known TP53 deletion >10% (17p del by FISH); intermediate risk – without TP53 deletion (≤10%) and with at least one of: unmutated IGHV genes and/or IGHV3‐21 usage, 11q deletion, β‐2 microglobulin ≥4 mg/l; good risk – none of the above and mutated IGHV genes (Oscier et al , 2010). Since then, several newer prognostic markers have been investigated in this trial: TP53 , SF3B1 and NOTCH1 mutations, and CLLU1 expression (Gonzalez et al , 2011, 2013; Oscier et al , 2013).…”

Section: Methodsmentioning

confidence: 99%

“…It includes an analysis of how second‐ and third‐line treatments might have contributed to the similarity of the survival curves across the three randomized treatment arms. Moreover, while the baseline prognostic factors for patients with CLL have been well studied and documented in this trial (Oscier et al , 2010, 2013; Gonzalez et al , 2011, 2013), the biological and treatment factors associated with patients who survive 10 years or more have not been previously reported. We include here 176 such patients with baseline biological, cytogenetic and molecular data and documented treatment histories, allowing us to consider the characteristics of these long‐term survivors.…”

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confidence: 93%

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The long‐term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years

et al. 2015

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SummaryWith 10+ years follow‐up in the Leukaemia Research Fund (LRF) CLL4 trial, we report the effect of salvage therapy, and the clinical/biological features of the 10‐year survivors treated for chronic lymphocytic leukaemia (CLL). Overall survival (OS) was similar in the three randomized arms. With fludarabine‐plus‐cyclophosphamide (FC), progression‐free survival (PFS) was significantly longer (P < 0·0001), but OS after progression significantly shorter, than in the chlorambucil or fludarabine arms (P < 0·0001). 614/777 patients progressed; 524 received second‐line and 260 third‐line therapy, with significantly better complete remission (CR) rates compared to first‐line in the chlorambucil arm (7% vs. 13% after second‐, 18% after third‐line), but worse in the FC arm (38% vs. 15% after both second and third‐line). OS 10 years after progression was better after a second‐line CR versus a partial response (36% vs. 16%) and better with FC‐based second‐line therapy (including rituximab in 20%) or a stem cell transplant (28%) versus all other treatments (10%, P < 0·0001). The 176 (24%) 10‐year survivors tended to be aged <70 years, with a “good risk” prognostic profile, stage A‐progressive, achieving at least one CR, with a first‐line PFS >3 years and receiving ≤2 lines of treatment. In conclusion, clinical/biological features and salvage treatments both influence the long‐term outcome. Second‐line therapies that induce a CR can improve OS in CLL patients.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 93%

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The long‐term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years

et al. 2015

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Chronic Lymphocytic Leukaemia

Dearden¹

2013

Encyclopedia of Life Sciences

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Chronic lymphocytic leukaemia (CLL) results from the expansion of a clone of CD5 + B lymphocytes with distinct morphology and membrane antigens. The clinical course is variable and is determined by the stage of the disease. A number of serum, immunological and genetic markers are important determinants of prognosis. Treatment is only indicated in symptomatic patients with active disease. Initial therapy for fit patients is usually with combination chemoimmunotherapy, whereas single alkylating agents continue to be used for those unable to tolerate more intensive treatments. The presence of TP 53 deletion, detected by fluorescence in situ hybridisation (FISH) analysis, predicts for poor response to conventional treatments and should be assessed in all patients before initiating therapy so that an alternative regimen can be selected. A number of new agents have shown activity in CLL. Key Concepts: CLL results from an expansion of clonal CD5 + CD19 + Blymphocytes with a unique diagnostic immunophenotype. The clinical course of CLL is highly variable with some patients surviving decades without treatment, whereas others may die within 3–5 years of diagnosis. Clinical stage and new laboratory markers give prognostic information. Patients whose CLL cells harbour TP 53 deletions or mutations have a particularly poor outcome. Patients with early stage asymptomatic disease do not require treatment. Combination chemoimmunotherapy is recommended for fit patients with no TP 53 abnormality. Single agent alkylator therapy (chlorambucil or bendamustine) is suitable for less fit patients. A number of newer agents are now available for management of relapsed/refractory patients. Where possible patients should be treated within a clinical trial. Allogeneic transplantation should be considered for younger fit patients with high‐risk disease. Care in the prevention and management of infections is crucial.

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Chronic Lymphocytic Leukemia

Hamblin¹,

Hamblin²

2011

Advances in Malignant Hematology

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Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation

Cited by 115 publications

References 33 publications

The long‐term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years

The long‐term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years

Chronic Lymphocytic Leukaemia

Chronic Lymphocytic Leukemia

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