Bone Marrow CD4+ and CD8+ Lymphocyte Infiltration Patterns Define Overall- and Progression Free Survival in Multiple Myeloma and May Predict IMiD Response: an Analysis from the Austrian Myeloma Registry

Abstract Introduction: In Multiple Myeloma immune dysregulation with quantitative and qualitative changes in T-cell subpopulations is thought to result in a reduced anti-tumour immune response promoting disease progression. Methods: A retrospective cohort of 45 myeloma patients was analyzed for the extent of tumor infiltrating CD4+ and CD8+ lymphocytes by means of immunohistochemistry using sophisticated automated evaluation software. Results: Here, for the first time we analyzed trephine biopsies of myeloma patients and we report a significant association of different patterns of immune cell infiltrations with OS and PFS suggesting that these patients might particularly benefit from immune modulating therapeutic strategies: CD4+ T-cells below a cutoff of 0.28% lymphocytes/total nucleated cells were associated with a significantly longer overall survival, while CD8+ T-cells above the cutoff of 6.51% predicted a longer progression free survival. Treatment with immunomodulatory drugs resulted in a significantly better overall- and progression free survival for patients with adverse local immunological features compared to those treated with proteasome inhibitors or non-novel agents. We suggest that immune dysregulation in myeloma significantly influences overall- and progression free survival. We will now validate this immuno algorithm of lymphocyte infiltration patterns as a predictive biomarker of IMiD responsiveness in the framework of a large randomized phase III trial. If confirmed they might be used as a putative biomarker to guide rational therapy allocation in the future. Disclosures Willenbacher: Celgene: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Willenbacher:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; European Commision: Research Funding. </jats:sec

Patients with double/triple copy number gains on C-MYC, BCL2, and/or BCL6 treated with standard chemotherapy have a similarly poor prognosis than those with high-grade B cell lymphoma with C-MYC and BCL2 and/or BCL6 rearrangements: a single-center experience on a consecutive cohort of large B cell lymphomas

AbstractHigh-grade B cell lymphomas with rearrangements on C-MYC and BCL2 and/or BCL6 (HGBL with MYC and BCL2 and/or Bcl6 rearrangement) are associated with worse clinical outcomes and thus were introduced as a separate new category in the recently updated WHO classification. From 2012 to 2016, we analyzed a consecutive cohort of large B cell lymphomas (LBCLs) for C-MYC, BCL2, and BCL6 rearrangements and correlated our results with clinical-pathological parameters. Ten of 78 (13%) cases had a C-MYC and BCL2 and/or BCL6 rearrangement, so-called double or triple hit (DH), while double/triple copy number gains (CNGs) were found in eight (10%) patients. Patients with a high-grade lymphoma with DH or CNG progressed significantly more often after first-line chemotherapy (p = 0.005). When treated with standard chemotherapy, patients with a DH or CNG had a significantly worse overall (OS) and recurrence free survival (RFS) compared with all other patients (p = 0.033 and p &lt; 0.001, respectively). Thus, patients with a diffuse large B cell lymphoma, harboring a double/triple CNG, seem to have a similar poor prognosis than those with a DH. Though our data can only be regarded as preliminary, our results warrant further investigations to fully elucidate the role of CNGs as well as underlying molecular mechanisms resulting in aggressive behavior in LBCL.</jats:p

Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR) Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics

Objective: Clinical trials demonstrate improving survival in patients with multiple myeloma (MM) after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting. Methods: We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR), focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide). Results: Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011–2014, 21% in patients with a diagnosis made between 2000–2005, and 39% in those with a diagnosis made between 2006–2010). For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide—so called IMiDs (from 2005 onwards) and their simultaneous use in combination therapies (from 2010 onwards) could be shown. The use of autologous transplantation (ASCT) remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105), showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%). Conclusion & Perspective With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM

Patient disposition in Multiple Myeloma patients diagnosed 2000–2005, 2006–2010 and 2011–2014.

Patient disposition in Multiple Myeloma patients diagnosed 2000–2005, 2006–2010 and 2011–2014.</p