Yttrium‐90 ibritumomab tiuxetan radioimmunotherapy in Richter syndrome

Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RS occurs in approximately 2% to 10% of CLL patients during the course of their disease, with a transformation rate of 0.5% to 1% per year. A combination of germline genetic characteristics, clinical features (eg, advanced Rai stage), biologic (ζ-associated protein-70+, CD38+, CD49d+) and somatic genetic (del17p13.1 or del11q23.1) characteristics of CLL B cells, and certain CLL therapies are associated with higher risk of RS. Recent studies have also identified the crucial role of CDKN2A loss, TP53 disruption, C-MYC activation, and NOTCH1 mutations in the transformation from CLL to RS. An excisional lymph node biopsy is considered the gold standard for diagnosis of RS; a 18F-fluorodeoxyglucose positron emission tomography scan can help inform the optimal site for biopsy. Approximately 80% of DLBCL cases in patients with CLL are clonally related to the underlying CLL, and the median survival for these patients is approximately 1 year. In contrast, the remaining 20% of patients have a clonally unrelated DLBCL and have a prognosis similar to that of de novo DLBCL. For patients with clonally related DLBCL, induction therapy with either an anthracycline- or platinum-based regimen is the standard approach. Postremission stem cell transplantation should be considered for appropriate patients. This article summarizes our approach to the clinical management of CLL patients who develop RS.

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“…74 Radioimmunotherapy with 90 Y ibritumomab tiuxetan was also tested in a pilot trial of 7 RS patients; however, no patient responded. 75 …”

Section: What Are the Treatment Options For Patients With Rs?mentioning

confidence: 99%

How we treat Richter syndrome

Parikh

Kay

Shanafelt

2014

Blood

154

146

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“…One option is to use consolidation or maintenance therapy, once that a CR or PR has been achieved by R-CHOP, OFAR or other regimens. Despite poor activity as single agents for induction treatment of RS [76,77], immunotherapy with rituximab and alemtuzumab or radioimmunotherapy may be attractive options for consolidation and maintenance therapy in RS patients in the context of multistep approaches already tested in CLL and DLBCL [78][79][80][81][82][83][84][85]. Approaches based on alemtuzumab or radioimmunotherapy should be considered investigative at the moment, and require testing in dedicated clinical trials.…”

Section: Treatment Of Richter Syndromementioning

confidence: 99%

Richter syndrome: molecular insights and clinical perspectives

Rossi

Gaïdano

2009

Hematological Oncology

108

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Richter syndrome (RS) represents the clinico-pathologic transformation of chronic lymphocytic leukaemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). The clinical definition of RS is heterogeneous, and encompasses at least two biologically different conditions: (i) CLL transformation to a clonally related DLBCL, that accounts for the majority of cases; (ii) development of a DLBCL unrelated to the CLL clone. In clonally related RS, the pathogenetic link between the CLL and the DLBCL phases is substantiated by the acquisition of novel molecular lesions at the time of clinico-pathologic transformation. RS is not a rare event in the natural history of CLL, since the cumulative incidence of RS at 10 years exceeds 10%. Prompt recognition of RS is known to be clinically useful, and may be favoured by close monitoring of CLL patients harbouring clinical and/or biological risk factors of RS development. Conventional risk factors that are independent predictors of RS development at the time of CLL diagnosis include: (i) expression of CD38; (ii) absence of del13q14 and (iii) lymph node size 3 cm. Other risk factors of RS development include CD38 genotype and usage of specific immunoglobulin variable genes. The molecular pathogenesis of RS has been elucidated to a certain extent. Acquisition of TP53 mutations and/or 17p13 deletion is a frequent molecular event in RS, as it is in other types of transformation from indolent to aggressive B-cell malignancies. Additional molecular alterations are being revealed by genome wide studies. Once that transformation has occurred, RS prognosis may be predicted by the RS score, based on performance status, LDH, platelet count, tumour size and number of prior therapies. Depending on patient's age and RS score, the therapeutic options for RS may range from conventional immunochemotherapy to allogeneic bone marrow transplantation.

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“…In our experience, other strategies, such as the radioimmunotherapeutic construct Y 90 ibritumomab tiuxetan, which is highly active in lymphoma, had no significant antitumor activity, but hematologic toxicity was severe in heavily pretreated patients with RS [51].…”

Section: Treatmentmentioning

confidence: 85%

Richter’s transformation in chronic lymphocytic leukemia

Tsimberidou

Keating²,

Wierda³

2007

Curr Hematol Malig Rep

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Richter's syndrome (RS) is the development of high-grade non-Hodgkin's lymphoma (NHL) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. This process may be triggered by viral infections (eg, Epstein-Barr virus infection), which are common in immunosuppressed patients. The large cells of RS either arise through a transformation of the original CLL clone or, less frequently, represent a new or secondary neoplasm. Karyotypic changes, including trisomy 12, chromosome 11 abnormalities, and multiple cell-cycle regulator disruptions, have been found in patients with RS. Although these genetic defects are believed to cause CLL cells to proliferate and, by facilitating the acquisition of new genetic abnormalities, to transform into RS cells, none appears predominantly responsible for the transformation. The prognosis is generally poor, and most patients do not have long-term (durable) responses to therapy. Rituximab and cytotoxic combination therapy followed by stem cell transplantation is associated with improved clinical outcome. Curative treatment strategies are needed.

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Yttrium‐90 ibritumomab tiuxetan radioimmunotherapy in Richter syndrome

Cited by 33 publications

References 28 publications

How we treat Richter syndrome

How we treat Richter syndrome

Richter syndrome: molecular insights and clinical perspectives

Richter’s transformation in chronic lymphocytic leukemia

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