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Although treatment options for multiple myeloma (MM) are rapidly evolving, there still remain difficult-to-treat situations, especially in relapsed and/or refractory (r/r) disease. When modern therapies are exhausted, or emergency treatment is needed for high tumor burden, classic chemotherapy combination regimens like the VTd-PACE regimen and its modifications (PACE-M) may also be beneficial as bridging to subsequent treatment options. This single-center retrospective analysis aimed to investigate the outcome of VTd-PACE and PACE-M salvage therapy in 31 heavily pretreated r/r MM patients. The primary objective was the overall response rate (ORR). Secondary objectives were median progression-free survival (mPFS), median overall survival (mOS), safety, and renal response. Median age was 59 years (range 39-75), and 71% of patients were male. R-ISS stratification showed high-risk MM in 48%. The median number of prior therapies was 3, with 23 patients being triple- and 12 penta-refractory (74% and 39%). ORR was 71%, including 23% of patients achieving a very good partial response. Median duration of follow-up was 15 months (range 0-29 months). mPFS and mOS were 3 months (95% CI 0.27-5.74) and 11 months (95% CI 3.66-18.35), respectively. In 26 patients (83.9%), at least one subsequent treatment (stem cell transplant or BCMA-directed) was administered. Renal function significantly improved after VTd-PACE or PACE-M treatment (p = 0.032). Non-hematological adverse events ≥ grade 3 were predominantly infections. VTd-PACE and PACE-M are effective salvage therapies in difficult-to-treat situations in heavily pre-treated r/r MM, including patients with impaired renal function. VTd-PACE and PACE-M can be successfully used as bridging therapy for subsequent treatment., (© 2022. The Author(s).)

Background: Multiple myeloma is a so far incurable malignant plasma cell disorder. During the past 2 decades, treatment paradigms substantially changed when novel drugs were introduced initially in treatment of relapsed disease and subsequently also in first-line treatment., Summary: Up to now, first-line treatment differs between patients initially classified as transplant eligible and those who are considered as nontransplant eligible. Transplant-eligible patients receive a primary proteasome inhibitor (PI)-based induction which is being combined with an immunomodulating agent and a CD38-directed monoclonal antibody followed by high-dose melphalan therapy and autologous stem cell transplantation with subsequent maintenance treatment with lenalidomide. Patients who are considered as nontransplant eligible receive upfront treatment preferentially with a continuous combination treatment either with a CD38-directed monoclonal antibody in combination with the immunomodulating agent lenalidomide or a lenalidomide-PI combination followed by lenalidomide maintenance. Key Messages: Primary goal of the initiated treatment is to induce a rapid and deep remission which ideally leads to an eradication of the residual plasma cell clone in sense of a minimal residual disease negativity. Achievement of long-term remission with limited toxicity despite continuous treatment strategies and maintenance or improvement of life-quality is key. Despite successful treatment options, specific difficult-to-treat subgroups, especially patients with high-risk myeloma remain with inferior prognosis and a clear unmet need for novel therapeutic strategies. Future concepts will evaluate cellular treatments and other innovative immunotherapies in first-line treatment in curative intention., (© 2021 S. Karger AG, Basel.)

Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in PCD patients, as compared to a healthy control group, and on possible influencing factors of serological responses. Blood samples were analyzed for the presence of quantitative anti-SARS-CoV-2 spike RBD Ig. A total of 82 patients were included; 67 received mRNA-, eight vector-based and four heterologous vaccinations. SARS-CoV-2 antibody titers (SP-AbT) were assessed in a mean of 23 days (SD ± 11 days) after the first and in a mean 21 days (SD ± 9) after prime-boost vaccination. A positive SP-AbT was detected in 31.9% of PCD patients after the first vaccination, and in 88.9% (44/49) after prime-boost vaccination, which was significantly less likely than that in the control group (100%, 78/78) (p = 0.008). Furthermore, we have been able to validate our previously suggested threshold of 30 CD19+ B lymphocytes/µL as being predictive for SP-AbT development. Despite anti-CD38 directed therapy, quadruplet treatment, higher age and missing deep remission, which correlated negatively with SP-AbT appearance, SP-AbT formation is possible in a majority of myeloma patients after prime-boost vaccination. [ABSTRACT FROM AUTHOR]

Simple Summary: The global impact of the current COVID-19 pandemic has led to the impressively rapid development of multiple anti-SARS-CoV-2 vaccines. However, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and, in particular, plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on multiple clinical factors including B lymphocyte count and current therapy of 82 patients with multiple myeloma and related plasma cell neoplasia, after the first dose of anti-SARS-CoV-2 vaccination. A positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts and current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination. Few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and particular, plasma cell neoplasia. This ongoing single-center study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma and related plasma cell dyscrasia, after the first dose of anti-SARS-CoV-2 vaccination. The 82 patients included in this study received SARS-CoV-2 vaccines (including mRNA- and vector-based vaccines) as a routine measure. After the first vaccination, a positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts. A cut-off value of ≥30 CD19+ B cells/µL was significantly positive correlating with higher SARS-CoV-2 SP-AbT. In contrast, current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease significantly correlated negatively with SARS-CoV-2 SP-AbT. Conversely, treatment with immunomodulatory drugs did not harm the development of antibody titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination. [ABSTRACT FROM AUTHOR]