Nationwide Investigation of Patient Trajectories in Mantle Cell Lymphoma - Initial Data from the Swedish MCL Complete Project

Background Mantle cell lymphoma (MCL) is a B-cell malignancy, with increasing incidence. It is currently not considered curable. Although a proportion of patients obtain prolonged remission after first line chemoimmunotherapy, most patients will experience several lines of therapy. Hitherto, population based data of the complete care trajectories for patients with MCL have not been available, limiting our knowledge to that from single centre experiences. Here, we present the initial data from a nationwide attempt to collect all available data from all patients diagnosed with MCL.

Methods Patients with a primary diagnosis of MCL in 2006-2018 were identified in the Swedish Lymphoma Register and followed until March 6, 2020. The register contains information about clinical characteristics, prognostic factors, primary treatment, treatment response and relapse. Information on further lines of therapy, including treatment response and progression/relapse was extracted through medical chart review in all patients.

Results In total, 1411 patients were diagnosed with MCL during the period 2006-2018. Currently, complete data are available for 445 (32%). The most frequently used first line regimens were R-bendamustine (n=131, 29%) and Nordic MCL2 (n=102, 21%). 31 patients (7%) were managed with an initial watch and wait strategy. 87 patients (19%) received consolidation with an autologous stem cell transplant, and 51 (11%) patients received rituximab maintenance. After a median follow-up of 49 months (IQR 25-81), 279 patients (63%) did not experience any relapse, and the median age for patients without relapse was higher compared to the relapse group (73 vs 70 years). 166 patients (37%) experienced a first relapse or progression. The most frequently used second line regimen was R-bendamustine (n=49, 30%). 102 (21%) and 51 (11%) experienced a second or third relapse/progression, respectively. The median PFS after 1^st (PFS-1), 2^nd, (PFS-2), 3^rd (PFS-3) and 4th (PFS-4) lines of therapy were 40, 11, 6, and 4 months. Patients with early progression, defined as a PFS-1 <24 months (POD24-1) had an inferior outcome (median OS of 23 vs. 101 months) compared to patients with a later relapse. Similarly, patients with a POD24-2 had an inferior outcome compared to patients with PFS-2 ³24 months (median OS 8.4 vs 61 months).

Conclusion In this population-based series, mainly treated with conventional chemoimmunotherapy, 63% of patients diagnosed with MCL did not experience relapse/progression after a median follow-up of 40 months – due to death before relapse or continuous remission. In addition, PFS and OS continue to drop with successive lines of therapies. Early progression, both after 1^st and after 2^nd line therapy is associated with markedly impaired OS –identifying patient populations in need of novel treatment strategies.

Figure 1 A. Progression-free survival (PFS) in 445 patients with mantle cell lymphoma (MCL) diagnosed in Sweden 2006-2018 according to first line regimen. B. Overall survival (OS) according to time to relapse (PFS -1 < 24 months or >24 months).