90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7\ua0years

Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan (90Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by 90Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma

High efficacy of the MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis, a 20 year experience

BACKGROUND: Adult Langerhans cell histiocytosis (LCH) is an orphan disease. Chemotherapy is usually reserved to patients presenting with single system multifocal (SS-m) or multisystem (MS) disease but due to the lack of randomized studies no standard first line therapy has been defined yet. Pediatric regimens based on the vinblastine/prednisone backbone are not well tolerated in adults and probably less effective. We previously demonstrated high efficacy of the dose dense polichemotherapy regimen MACOP-B in 7 adult patients with SS-m or MS-LCH, in terms of high response rate and durable responses. Here we report an update of these data with the purpose of evaluating the long term efficacy of MACOP-B in adult LCH. METHODS: Clinical data of all adult LCH patients (n = 17) diagnosed and treated at our Institution during the past 20-year period were retrospectively reviewed. RESULTS: A total of 11 patients (6 with SS-m and 5 with MS-LCH) were treated with MACOP-B from 1995 to 2014. The overall response rate was confirmed to be 100 %, with a complete response of 73 % and a partial response rate of 27 %. Overall progression free survival was 64 %, and disease free survival after achievement of initial CR was 87 %. Overall survival rate was 82 % after 6.7 years of median follow-up. CONCLUSIONS: These data confirm high activity of MACOP-B in adult LCH, indicating that a substantial fraction of patients achieve long lasting responses and can be cured with this therapeutic approach

Interesting activity of pegylated liposomal doxorubicin in primary refractory and multirelapsed Hodgkin lymphoma patients: Bridge to transplant

Most patients with classical Hodgkin lymphoma (cHL) can be cured with frontline therapy, and those with relapsed or refractory (R/R) disease can often be cured with salvage therapy and autologous stem cell transplantation (ASCT).1-3 However, the prognosis of patients who relapse after or are ineligible to ASCT has historically been extremely poor, with a median overall survival of just over 2 years.1-3 Achieving durable responses in this patient population is a critical treatment goal so far only rarely achieved with conventional chemotherapy.4,5 Brentuximab vedotin (BV) has demonstrated efficacy in patients treated after failure of ASCT, with objective responses seen in 75% of patients in a phase 2 study.6 Recently, because of the unique genetics of cHL, the check point inhibitors nivolumab and pembrolizumab were tested in phase 1 to 2 studies that demonstrated objective responses in 70% to 85% heavily pretreated patients with R/R cHL.7-10 Among the different conventional salvage chemotherapy regimens and conventional single agents, such as bendamustine, BV, nivolumab, and pembrolizumab, there is another drug with interesting results in the setting of R/R cHL, but less known and used: the pegylated liposomal doxorubicin (PLD

Long-term responders after Brentuximab vedotin: Single-center experience on relapsed and refractory hodgkin lymphoma and anaplastic large cell lymphoma patients

Background. Brentuximab vedotin (BV) has shown high overall response rate in refractory/relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) with reported long-term response duration in clinical trials, but few data are available regarding its role in long-term outcomes in real life. PATIENTS AND METHODS: A single-center observational study was conducted on patients treated with BV in daily clinical practice to evaluate the long-term effectiveness of BV in HL and sALCL patients and to check whether clinical trial results are confirmed in a real-life context. RESULTS: The best response rate in the treated 53 patients (43 HL and 10 sALCL) was 69.8% (with 46.5% complete response [CR]) in HL and 100% (80% CR) for sALCL, respectively. With a median patient follow-up of 36.8 months, the estimated median duration of response was 31.5 months for HL and 17.8 for sALCL, respectively. At the latest available follow-up, 75% of patients were still in response, with 43% without any consolidation. Toxicity was primarily neurological and it was rarely so serious to require dose reduction or interruption. In addition, it always reversed completely after the end of treatment. CONCLUSION: Our data showed that 51% of patients treated with BV can be regarded as \u201clong-term responders.\u201d Among these cases, for all patients who underwent stem cell transplantation immediately after BV, the procedure was consolidative. For patients who have remained in continuous CR without any consolidation after therapy, BV can induce prolonged disease control

The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients

Abstract Background The purpose of this study is to investigate the most suitable first-line approach and the best combination treatment for primary mediastinal large B-cell lymphoma (PMLBCL) as they have been matter of debate for at least two decades. Methods Our single centre experience in the treatment of 98 de novo PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy; 30 were irradiated after chemotherapy, although not receiving rituximab and 20 received rituximab without radiotherapy consolidation. Eleven patients received chemotherapy only. Results Sixty-one (62.2%) patients achieved a complete response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial responders, 21 obtained a complete response after radiotherapy. At the end of their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial response (6.1%). Eleven patients relapsed within the first 2 years of follow-up. The 17-year overall survival is 72.0% (15 patients died); progression-free and disease-free survival are 67.6% and 88.4%, respectively. A statistically significant difference in overall and progression-free survival was noted among treatment groups, although no disease-free survival difference was documented. Conclusions Our data indicate that a third-generation regimen like MACOP-B could be considered a suitable first-line treatment. Mediastinal consolidation radiotherapy impacts on survival and complete response rates and remains a good strategy to convert partial into complete responses. Data suggest that radiotherapy may be avoided in patients obtaining a complete response after (immuno)chemotherapy, but this requires confirmation with further ad hoc studies

High efficacy of the MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis, a 20 year experience

Adult Langerhans cell histiocytosis (LCH) is an orphan disease. Chemotherapy is usually reserved to patients presenting with single system multifocal (SS-m) or multisystem (MS) disease but due to the lack of randomized studies no standard first line therapy has been defined yet. Pediatric regimens based on the vinblastine/prednisone backbone are not well tolerated in adults and probably less effective. We previously demonstrated high efficacy of the dose dense polichemotherapy regimen MACOP-B in 7 adult patients with SS-m or MS-LCH, in terms of high response rate and durable responses. Here we report an update of these data with the purpose of evaluating the long term efficacy of MACOP-B in adult LCH.Background: Adult Langerhans cell histiocytosis (LCH) is an orphan disease. Chemotherapy is usually reserved to patients presenting with single system multifocal (SS-m) or multisystem (MS) disease but due to the lack of randomized studies no standard first line therapy has been defined yet. Pediatric regimens based on the vinblastine/prednisone backbone are not well tolerated in adults and probably less effective. We previously demonstrated high efficacy of the dose dense polichemotherapy regimen MACOP-B in 7 adult patients with SS-m or MS-LCH, in terms of high response rate and durable responses. Here we report an update of these data with the purpose of evaluating the long term efficacy of MACOP-B in adult LCH. Methods: Clinical data of all adult LCH patients (n = 17) diagnosed and treated at our Institution during the past 20-year period were retrospectively reviewed. Results: A total of 11 patients (6 with SS-m and 5 with MS-LCH) were treated with MACOP-B from 1995 to 2014. The overall response rate was confirmed to be 100%, with a complete response of 73% and a partial response rate of 27%. Overall progression free survival was 64%, and disease free survival after achievement of initial CR was 87%. Overall survival rate was 82% after 6.7years of median follow-up. Conclusions: These data confirm high activity of MACOP-B in adult LCH, indicating that a substantial fraction of patients achieve long lasting responses and can be cured with this therapeutic approach

The Berlin-Frankfurt-M\ufcnster protocol for the upfront treatment of aggressive lymphomas: The Bologna experience

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