Rare lymphomas in routine practice-Treatment and outcome in Waldenström's macroglobulinaemia in the prospective German Tumour Registry Lymphatic Neoplasms.

Waldenström's macroglobulinaemia (WM) is a rare indolent B-cell lymphoma for which only little prospective phase III evidence exists. Thus, real world data are important to provide insight into treatment and survival. We present here data on choice and outcome of systemic treatment of patients with WM treated in German routine practice. In total, 139 patients with WM who had been documented in the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms (NCT00889798) were included into this analysis. We analysed the most frequently used first-line and second-line treatments between 2009 and 2017 and examined best response, progression-free survival (PFS) and overall survival (OS). Bendamustine plus rituximab, with a median of six cycles, was by far the most frequently used first-line treatment (81%). Second-line treatment was more heterogenous and mainly based on bendamustine, cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP), fludarabine or ibrutinib, the latter approved in 2014. Three-year PFS from start of first-line treatment was 83% (95% confidence interval [CI] 74%-88%), 3-year OS was 87% (95% CI 80%-92%). These prospective data give valuable insights into the management and outcome of non-selected patients with WM treated in German routine practice. In the lack of prospective phase III clinical trials, real world data can help bridging the gap of evidence.

Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera.

To further characterize JAK2 exon 12 mutations, we performed molecular screening in 409 patients with polycythemia vera or unclear erythrocytosis with unmutated JAK2V617. The frequency of JAK2exon12 mutations was 10/63 (15.9%) in PV but only 5/346 (1.4%) in the erythrocytosis cases. Nine different mutations including four new types (D544-L545del, H538DK539LI540S, H538-K539del, V536-F547dup) were detected. In 2 cases we found evidence for the presence of cells homozygous for mutated JAK2exon12. As this was the case in only 2/15 cases with JAK2exon12 mutations (13%) homozygosity seemed to be less frequent than in V617F-mutated polycythemia vera (69%) (p<0.001). There were more females than males in the group of patients with a JAK2exon12 mutation (10 vs. 5) compared to the group with wildtype JAK2 (132 vs. 262; p=0.012). Median age of onset was lower than in the V617Fmut controls (58.5 vs. 67.8 years, p<0.001). In conclusion, JAK2 exon 12 mutation analysis contributes to diagnostics in polycythemia vera or erythrocytosis.