Nationwide Assessment of Patient Trajectories in Mantle Cell Lymphoma: The Swedish MCLcomplete Project.

Mantle cell lymphoma (MCL) is a B-cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first-line chemoimmunotherapy, many will need several treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006-2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression-free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow-up was 6.8 years. Two hundred and one (15%) were managed initially with watch-and-wait, but 1235 (90%) eventually received treatment. The most frequently used first-line regimens were rituximab-bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow-up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second-line treatment. The most frequently used second-line regimen was BR (n = 185; 34%) but otherwise a wide variety of second-line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS-1), second (PFS-2), third (PFS-3), and fourth (PFS-4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS-1 <24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population-based data, we provide important benchmarks for future studies of all treatment lines in MCL.

Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström's Macroglobulinemia.

PURPOSE: Rituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM. METHODS: In this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety. RESULTS: Two hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC (P = .32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P < .01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade ≥ 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC. CONCLUSION: This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.

Clinical characteristic and outcome of lymphoplasmacytic lymphoma of non-Waldenstrom macroglobulinemia type: A Swedish lymphoma registry study.

Lymphoplasmacytic lymphoma (LPL) not fulfilling the WHO diagnostic criteria (2017) for Waldenstrom's macroglobulinemia (WM) (named non-WM LPL) is a rare disease and only a few systematic studies have been published. Here, we present a population-based study of non-WM LPL focusing on diagnostic difficulties, patient characteristics, and outcome. From 1511 patients included in the Swedish Lymphoma Registry 1 Jan 2000 - 31 Dec 2014 with a diagnosis of WM/LPL, we could confirm the diagnosis of non-WM LP in only 33 patients. The median age at diagnosis was 69 years. A paraprotein was found in most (IgG in 54%, IgA in 15%) and 12% of the cases were non-secretory. Compared with the WM patients, the non-WM LPL patients were younger, had more adverse prognostic factors such as elevated LDH, anaemia, and lymphocytosis at diagnosis. In addition, the non-WM LPL patients more often were symptomatic and received treatment at diagnosis. The overall survival (OS) did not significantly differ between the non-WM LPL and WM groups (P = 0.247), with a median survival time of 71 and 96 months, respectively. To conclude, we found differences in clinical features between WM and non-WM LPL, but no difference in survival.

Prognostic factors and primary treatment for Waldenström macroglobulinemia - a Swedish Lymphoma Registry study.

We present a nationwide prospective Swedish registry-based study of Waldenström macroglobulinaemia (WM), that focuses on incidence and survival in relation to clinical prognostic factors and primary systemic therapies. A total of 1511 patients with WM and lymphoplasmocytic lymphoma (LPL) were registered in the Swedish Lymphoma Registry (SLR) between 1 January 2000 and 31 December 2014. The age-adjusted incidence of WM/LPL was 11·5 per million persons per year, three times higher than the reported incidence worldwide. Medical records were retrieved for 1135 patients (75%). A retrospective review showed that 981 (86·1%) of these patients fulfilled the World Health Organization diagnostic criteria for WM and these patients were analysed further. The overall survival (OS) improved between two periods - 2000-2006 and 2007-2014 - with a five-year OS of 61% and 70%, respectively. Significant prognostic factors for OS, evaluated at the time of diagnosis, were age, elevated lactate dehydrogenase level and haemoglobin ≤115 g/l for patients receiving therapy 0-3 months after diagnosis, and age, poor performance status, haemoglobin ≤115 g/l, and female sex in "watch and wait" patients (multivariable analysis). The level of the IgM monoclonal immunoglobulin had no significant prognostic value. Rituximab included in first-line therapy was associated with improved survival.

Familial Waldenstrom's macroglobulinemia and relation to immune defects, autoimmune diseases, and haematological malignancies--A population-based study from northern Sweden.

BACKGROUND: Waldenstrom's macroglobulinemia (WM) is a rare lymphoprolipherative disorder with geographic and ethnic disparities in incidence. The cause of WM remains mostly unknown although a role for genetic, immune-related, and environmental factors has been suggested. Most cases of WM are sporadic although familial cases occur. AIM: This study estimated the incidence of WM in northern Sweden and identified and described patients with familial WM in this area. PATIENTS AND METHODS: The Swedish and Northern Lymphoma Registry, the Swedish Cancer Registry (1997-2011), and medical records were used to identify patients with WM in two counties (Norrbotten and Västerbotten) in northern Sweden and to calculate the overall age-adjusted incidence (2000-2012). We identified 12 families with a family history of WM, IgM monoclonal gammophathy (MGUS), and/or multiple myeloma (MM). RESULTS: In Norrbotten and Västerbotten, the age-adjusted incidence of WM/LPL is 1.75 and 1.48 per 100,000 persons per year, respectively (2000-2012), rates that are higher than the overall incidence of WM/LPL in Sweden (1.05 per 100,000 persons per year; 2000-2012). Autoimmune diseases and other haematological malignancies in the medical history (their own or in relatives) were reported in 9/12 and 5/12 families, respectively. A high proportion of abnormal serum protein electrophoresis was found in the relatives; 12/56 (21%) had a MGUS and 13/56 (25%) showed abnormalities in the immunoglobulin levels (i.e. subnormal levels and poly/oligoclonality). CONCLUSION: The incidence of WM in Norrbotten and Västerbotten counties was higher than expected. We found a strong correlation between autoimmune/inflammatory diseases, other haematological malignancies, and familial WM and a high frequency of serum immunoglobulin abnormalities in the relatives of the WM patients, findings that strengthen the hypothesis that the aetiology of WM depends on both immune-related and genetic factors.