What is the optimal initial management of the older MCL patient?

The current first line treatment of a patient with mantle cell lymphoma (MCL) is often considered as too toxic for elderly patients. The elderly, however, comprise the majority of the patients with MCL. The results of several recent studies have shown that the outcome of this patient group is not as dismal as in the past. Indeed, if patients are not considered frail, and can tolerate rituximab and moderate intensive chemotherapy such as R-CHOP followed by rituximab maintenance or R-bendamustine, a 4-year overall survival of >80% can be achieved. In this chapter the developments of the regimens, resulting in the standard treatment options for these patients, are discussed. (C) 2017 Elsevier Ltd. All rights reserved

Nieuwe ontwikkelingen voor patienten met geavanceerde systemische mastocytose

Geavanceerde systemische mastocytose is een kleine subgroep van ziektebeelden binnen systemische mastocytose (SM), waar vooral hematologen mee te maken krijgen. Tot geavanceerde SM worden agressieve SM, SM met bijkomende hematologische neoplasie (SM-AHN) en mestcelleukemie (MCL) gerekend. De laatste jaren zijn er belangrijke diagnostische, prognostische en therapeutische ontwikkelingen. Behalve de KIT-mutatie blijken vele andere mutaties voor te komen die onder meer prognostisch sterk voorspellend zijn voor de overleving. Na een wereldwijde fase 2-studie waaraan ook vanuit Nederland is geparticipeerd, is midostaurin (onder meer een c-KITblokker) geregistreerd voor deze groep patiënten, omdat er niet alleen veel responsen werden waargenomen, maar er ook overlevingswinst werd behaald. Desalniettemin zijn er geen complete remissies bereikt en zal allogene stamceltransplantatie voor een hoogrisicogroep een belangrijke mogelijkheid zijn. Momenteel wordt binnen Europees verband gewerkt aan nieuwe studies. De verwachting is dat Nederland wederom een belangrijke bijdrage zal leveren

Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma:Results from the European Mantle Cell Lymphoma Elderly Trial

PURPOSE The outcome of older patients with mantle cell lymphoma (MCL) has improved by the introduction of immunochemotherapy, followed by rituximab (R)-maintenance. Assessment of minimal residual disease (MRD) represents a promising tool for individualized treatment decisions and was a prospectively planned part of the European MCL Elderly trial. We investigated how MRD status influenced the efficacy of R-maintenance and how MRD can enable tailored consolidation strategies.PATIENTS AND METHODS Previously untreated patients with MCL age 60 years or older have been randomly assigned to R versus interferon-alpha maintenance after response to rituximab, fludarabine, cyclophosphamide (R-FC) versus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). MRD monitoring was performed by real-time quantitative polymerase chain reaction (qPCR) following EuroMRD guidelines.RESULTS A qPCR assay with a median sensitivity of 1 × 10-5 could be generated in 80% of 288 patients in an international, multicenter, multilaboratory setting. More extensive tumor dissemination facilitated the identification of a molecular marker. The efficacy of R-maintenance in clinical remission was confirmed for MRD-negative patients at the end of induction in terms of progression-free survival (PFS; hazard ratio [HR], 0.38 [95% CI, 0.21 to 0.63]) and overall survival (OS; HR, 0.37 [95% CI, 0.20 to 0.68]), particularly in R-CHOP-treated patients (PFS-HR, 0.23 [95% CI, 0.10 to 0.52]; OS-HR, 0.19 [95% CI, 0.07 to 0.52]). R-maintenance appeared less effective in MRD-positive patients (PFS-HR, 0.51 [95% CI, 0.26 to 1.02]) overall and after R-CHOP induction (PFS-HR, 0.59 [95% CI, 0.28 to 1.26]). R-FC achieved more frequent and faster MRD clearance compared with R-CHOP. MRD positivity in clinical remission after induction was associated with a short median time to clinical progression of approximately 1-1.7 years.CONCLUSION The results confirm the strong efficacy of R-maintenance in patients who are MRD-negative after induction. Treatment de-escalation for MRD-negative patients is discouraged by our results. More effective consolidation strategies should be explored in MRD-positive patients to improve their long-term prognosis.</p

Persistent improved results after adding vincristine and bleomycin to a cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III-IV intermediate- and high-grade non-Hodgkin's lymphoma

SCOPUS: cp.jinfo:eu-repo/semantics/publishe