Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy.

The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O-ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O-ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0·001), bulky disease (P < 0·001) and B symptoms (P < 0·001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O-ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O-ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte-predominant HL.

Ability of final PET/CT to predict response to first-line treatment in real patients with classical Hodgkin lymphoma.

Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / - radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher's exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.

Management experience of advanced-stage mycosis fungoides/Sézary syndrome: a retrospective study from Spanish haematology referral units.

BACKGROUND: Advanced-stage mycosis fungoides/Sézary syndrome (aMF/SS) has a dismal outcome. The only curative treatment is allogeneic stem cell transplantation (allo-SCT) but this is limited to selected candidates, thus palliative therapy is the most frequent strategy. OBJECTIVES: To describe the characteristics of aMF/SS in cases referred to haematology units for advanced/palliative therapy. MATERIALS AND METHODS: Data from 30 patients were collected from four centres, and descriptive statistics, frequencies and survival analyses were calculated. RESULTS: Eighty-eight per cent of patients received systemic therapy. The median number of therapies was three (range: 1-9). Bexarotene (21%), CHOP-like chemotherapy (10%) and methotrexate (9%) were the more common treatments. The overall survival at a median follow-up of 28 months (range: 8-65 months) for aMF/SS was 56.9%. Survival probability was more favourable for MF (p < 0.02). Nine patients received allo-SCT. Half of the patients (56%) relapsed after allo-SCT but could be rescued with immunosuppression tapering, donor lymphocyte infusions and additional therapy (80%). CONCLUSION: There is significant heterogeneity in aMF/SS treatments. Survival is more favourable for MF compared to SS. Current chemoimmunotherapies are insufficient to control disease, making allo-SCT the best therapeutic approach in selected patients.

Evaluation of clinical and biological prognostic factors in relapsed or refractory diffuse large B-cell lymphoma patients after previous treatment with rituximab and chemotherapy: results of the PRO-R-IPI study.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing a highly variable outcome. In patients with DLBCL relapsed/refractory to first-line treatment with rituximab the usefulness of the revised International Prognostic Index (R-IPI) as a prognostic tool remains unexplored. Some biological parameters (B-cell lymphoma 6 [Bcl-6], Bcl-2, p53, and multiple myeloma 1 [MUM1]) and blood populations (lymphocyte and monocyte counts) have been described as International Prognostic Index-independent prognostic factors. The objective was to evaluate the R-IPI to predict the outcome of DLBCL patients at the time of relapse after a front-line treatment with chemotherapy and rituximab and to establish in this population the relationship between biological parameters and outcome. PATIENTS AND METHODS: We included patients with refractory/relapsed DLBCL after first-line treatment with rituximab-containing regimens; patients must have already finished a rescue treatment also including rituximab. Immunohistochemical assessment of Bcl-2, Bcl-6, p53, and MUM1 expression were undertaken in available biopsies. R-IPI factors were identified from the clinical data at diagnosis and at relapse. Response was assessed using National Cancer Institute-sponsored Working Group guidelines. RESULTS: R-IPI prognosis at relapse was not significantly associated with overall response rate (ORR) after Rituximab-chemotherapy rescue therapy. None of the immunohistochemical parameters analyzed correlated with rescue therapy results. In contrast, patients with absolute lymphocyte count (ALC) ≥ 1 × 10(9)/L at relapse were more likely to respond than patients with ALC < 1 × 10(9)/L (P = .05). CONCLUSION: The R-IPI score calculated at relapse could not predict the ORR to second-line treatment. Lymphopenia is a simple and useful predictor for outcome in relapsed/refractory DLBCL and the only prognostic factor that in our hands could predict the overall response to a second-line treatment with rituximab and chemotherapy.