The long‐term outcome of patients in the <scp>LRF CLL</scp>4 trial: the effect of salvage treatment and biological markers in those surviving 10 years

Else, Monica; Wade, Rachel; Oscier, David; Catovsky, Daniel

doi:10.1111/bjh.13824

Cited by 13 publications

(16 citation statements)

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“…Interestingly, in this study the majority of patients with an EBV positive biopsy had been previously treated with fludarabine. However, a hypothetic relationship between fludarabine and RS was not confirmed by recent studies that evaluated the rate of RS cases according to the type of initial therapy …”

Section: Discussionmentioning

confidence: 96%

Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma

et al. 2017

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We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%. Prior treatment for CLL had been received by 82% of patients and included fludarabine in 67%. Coexistence of CLL and HL was detected in the same bioptic tissue in 87% of cases. The most common administered treatment was the ABVD regimen given to 22 patients (66.6%). The complete response (CR) rate after ABVD was 68%, and was influenced by the IPS (P = .03) and interval from the last CLL treatment (P = .057). Survival from HL was also influenced by the IPS (P = .006) and time from the last CLL treatment (P = .047). The achievement of CR with ABVD was the only significant and independent factor predicting survival (P = .037). Taken together, our results show that the IPS and the interval from the prior CLL treatment influence the likelihood of achieving CR after ABVD, which is the most important factor predicting survival of patients with CLL developing HL.

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Section: Discussionmentioning

confidence: 96%

Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma

et al. 2017

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“…Furthermore, updated results from the CLL5 trial showed a prolonged survival in patients treated with chlorambucil compared with those who received fludarabine (68.1 months versus 49.8 months, respectively) [Eichhorst et al 2009]. Similar data were reported with the long-term follow up from the CLL4 trial comparing chlorambucil with fludarabine and FC [Else et al 2015]. After 10 years observation of the survivors, OS did not differ among patients treated with chlorambucil compared with FC or the fludarabine arm; this could be explained taking into account the fact that a significantly better complete response rate was obtained following first-line chlorambucil or fludarabine progression, when compared with those who received FC as first line.…”

Section: Overview On Complement1 Trial Data and Chlorambucil-based Chmentioning

confidence: 73%

Ofatumumab plus chlorambucil as a first-line therapy in less fit patients with chronic lymphocytic leukemia: analysis of COMPLEMENT1 and other monoclonal antibodies association data

Frustaci

Tedeschi

Picardi

et al. 2016

Therapeutic Advances in Hematology

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Abstract:The management of patients with chronic lymphocytic leukemia (CLL) has radically improved over the last few years with the addition of anti-CD20 monoclonal antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades as a suitable therapeutic option for frail patients. Taking into account the advantage offered by the addition of MoAbs to chemotherapy, different studies up to now have explored the feasibility of chlorambucilbased chemoimmunotherapies in treatment-naïve CLL. COMPLEMENT1 is a prospective, randomized, open-label trial evaluating the efficacy and safety of ofatumumab added to chlorambucil, compared with chlorambucil in monotherapy, in the setting of untreated patients with CLL considered unsuitable for a fludarabine-based approach. Progression-free survival was significantly longer in the chemoimmunotherapy arm when compared with the single-agent chlorambucil (22.4 months versus 13.1 months). Response rate and quality were also improved in the combination arm. Furthermore, the addition of ofatumumab did not lead to an unmanageable toxicity. While the employment of anti-CD20 antibodies represents an advantage in the treatment of the CLL symptomatic population, at present different patient selection and treatment schedules do not allow a reliable comparison between chlorambucilbased regimens. The addition of ofatumumab to chlorambucil represents a further therapeutic gain in CLL. Longer follow up and direct comparison with other MoAbs are warranted to establish the preferred first-line treatment in elderly and unfit patients.

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“…In randomized trials, single agent fludarabine or bendamustine have shown significant improvement over chlorambucil alone [57,58]. Combination of fludarabine with cyclophosphamide (FC) or cladribine with cyclophosphamide (CC) has shown improvement in the overall response rate (ORR) and progression free survival (PFS) compared to single agent therapy [59][60][61]. A major breakthrough came in late 1990's with the advent of rituximab.…”

Section: Evolution Of Treatment Of Cll (Then and Now In 2016)mentioning

confidence: 99%

Chronic lymphocytic leukemia (CLL)—Then and now

Kanti

Jain²

2016

American J Hematol

137

108

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The field of chronic lymphocytic leukemia (CLL) has witnessed considerable change since the time clinical staging was introduced in clinical practice in 1975. Over the years, the prognostication in CLL has expanded with the addition in late 90s of mutational status of variable region of immunoglobulin heavy chain (IGHV), and chromosomal analyses using fluorescent in situ hybridization (FISH). More recently, stereotypy of BCR (B cell receptor) and whole exome sequencing (WES) based discovery of specific mutations such as NOTCH1, TP53, SF3B1, XPO-1, BIRC3, ATM, and RPS15 further refined the current prognostication system in CLL. In therapy, the field of CLL has seen major changes from oral chlorambucil and steroids prior to 1980s, to chemo-immunotherapy (CIT) with fludarabine, cyclophosphamide, rituximab (FCR) to the orally administered targeted therapeutic agents inhibiting kinases in the B cell receptor (BCR) signaling pathway such as Ibrutinib (BTK inhibitor) and Idelalisib (p110 PI3Kd inhibitor) and novel anti-CD20 mAb's (monoclonal antibodies) such as obinutuzumab. This progress is continuing and other targeted therapeutics such as Bcl2 antagonists (Venetoclax or ABT-199) and finally chimeric antigen receptor against T cells (CART) are in the process of being developed. This review is an attempt to summarize the major benchmarks in the prognostication and in the therapy of CLL. The topic allocated to us by Dr Ayalew Tefferi and Dr Carlo Brugnara is very appropriate to reminisce what our understanding of chronic lymphocytic leukemia (CLL) was in 1976 and how rapidly have the advances occurring in this field affected the patients with CLL. It is a disease of progressive accumulation of lymphocytes. CLL lymphocytes are morphologically indistinguishable from a normal mature lymphocyte CLL lymphocytes are functionally inert and perhaps as a direct consequence, their life-span is longer than of normal lymphocytes. It was also believed that CLL lymphocytes are not rapidly proliferating. CLL is a disease of elderly population In some cases, chronic lymphocytic leukemia (CLL) closely resembled leukemic Brill Symmers disease (leukemic form of follicular lymphoma). In an elegant study on 88 patients, the temporal profile of the clinical course of CLL was described by Galton et al.[1] Disease progression was assessed in relation to lymphadenopathy, splenomegaly and bone marrow infiltration. CLL was considered as an immunoproliferative disorder with low immunoglobulin levels, striking response to therapy with steroids and exaggerated skin reaction to arthropod bites. Management of CLL (then in 1976)Most clinicians recognized that at the time of initial diagnosis, patients with CLL, generally, were free of disease-related symptoms. Therefore, virtually all patients were followed on a wait-and-watch regimen, withholding any cytotoxic therapy. When, on clinical grounds, initiation of any therapy was considered appropriate, oral alkylating agents such as chlorambucil with/without steroids [3,4] or cyclophosphamide [5] with or...

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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

Cited by 13 publications

References 29 publications

Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma

Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma

Ofatumumab plus chlorambucil as a first-line therapy in less fit patients with chronic lymphocytic leukemia: analysis of COMPLEMENT1 and other monoclonal antibodies association data

Chronic lymphocytic leukemia (CLL)—Then and now

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