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Multiple myeloma (MM), a malignant plasma cell disorder, is still an incurable disease. Thus, the identification of novel therapeutic targets is of utmost importance. Here, we evaluated the peripheral blood-based metabolic profile of patients with MM. Peripheral blood plasma levels of 188 endogenous metabolites, including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingomyelins, and hexoses were determined in patients with plasma cell dyscrasias: monoclonal gammopathy of undetermined significance, a precursor stage of MM (MGUS, n = 15), newly diagnosed MM, (NDMM, n = 32), relapsed/refractory MM (RRMM, n = 19) and in 25 healthy controls by mass spectrometry. Patients with NDMM, RRMM and MGUS have a substantially different metabolomic profile than healthy controls. The amount of eight plasma metabolites significantly differs between the NDMM and MGUS group: free carnitine, acetylcarnitine, glutamate, asymmetric dimethylarginine (ADMA) and four phosphatidylcholine (PC) species. In addition, the levels of octadecanoylcarnitine, ADMA and six PCs were significantly different between RRMM and MGUS patients. 13 different concentrations of metabolites were found between RRMM and NDMM patients (free carnitine, acetylcarnitine, creatinine, five LysoPCs and PCs). Pathway analyses revealed a distinct metabolic profile with significant alterations in amino acid, lipid, and energy metabolism in healthy volunteers compared to MGUS/MM patients. We identified different metabolic profiles in MGUS und MM patients in comparison to healthy controls. Thus, different metabolic processes, potentially the immunoregulation by indoleamine 2,3 dioxygenase-1 (IDO), which is involved in cancer development and progression supporting inflammatory processes in the tumor microenvironment and glutaminolysis, can serve as novel promising therapeutic targets in MM.

Allogeneic hematopoetic stem cell transplantation (allo SCT) is a treatment option with a unique chance of cure for patients with high-risk AML or MDS. However, the optimal path for an individual patient on its way to allo SCT is far from clear and subject of ongoing debates. Upfront transplantation “as soon as possible” competes with strategies to achieve deep remission or at least stabilization of the disease. In this context, we performed a survey among German transplant centers to assess their preferred strategies for patients before SCT in five typical scenarios of AML and MDS. We obtained replies from 22 centers, revealing a heterogenous use of possible strategies. Upfront transplantation was a preferred option (68%) in intermediate risk MDS, chemotherapy was preferred (64%) as bridging for AML in remission, whereas hypomethylating agents (HMA) and induction chemotherapy for relapsed AML were highly controversial. Further prospective evaluation of different options is desirable.

Background: Treatment of multiple myeloma has advanced tremendously with the approval of anti-CD38 antibodies. Their efficacy is impressive but still controversial in the 1q amplification subgroup (amp1q). This retrospective study aims to provide real-world data. Methods: This trial is analyzing 74 patients with relapsed/refractory multiple myeloma treated with CD38Abs at the Medical University of Innsbruck (2016–2023). High-risk (HR) cytogenetics according to R-ISS (t(4;14), t(14;16), t(14;20), del(17p)), the presence of amp(1q21), the frequency of two HR markers (double hit), and the high-risk criteria agreed at IMS 2024 (HR-IMS24) were considered. Results: The median age of the 74 patients (62.1% male) was 62 years, with a median follow-up of six years. Most patients received third-line therapy (37.8%). R-ISS HR was documented in 39.2% of patients, double hit in 13.5% of patients, and HR-IMS24 in 32.4% of patients, while amp1q was detected in 35.1% of patients. The median OS was 66 months (35–89), and the median PFS was 17 months (6.5–26.9). While neither R-ISS HR nor isolated amp1q had an impact on progression-free survival (e.g., amp1q 7.03: 1.95–22.44; p = 0.347), the occurrence of a double-hit pattern significantly impaired PFS and OS (6.2: 1.4–16.4 months; p = 0.044; OS, 42.8: 25.9–74.6 months; p = 0.035). Patients fulfilling the HR-IMS24 criteria (32.4%, 24 patients) also exhibited an impaired PFS and OS (7: 2.7–18.1 months, p = 0.023; 40.12: 21.1–74.5 months, p = 0.01). Conclusions: This retrospective study highlights the durable effect of daratumumab on cytogenetic abnormalities, particularly amp1q. However, patients who meet the criteria for double-hit myeloma or the high-risk IMS2024 criteria remain a difficult-to-treat patient population who require early access to new treatment approaches.

Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA. Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood). High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies.

Adult acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a rare and heterogeneous malignancy characterized by uncontrolled proliferation of B or T cell precursor cells. Here, we retrospectively analyzed the outcome of early autologous stem cell transplantation in standard-risk patients in first complete remission (n=24) and of allogeneic transplantation in high and highest risk, and relapsed/refractory patients (n=35). The 10-year overall survival after autologous transplantation was 45%. The 10-year overall survival after allogeneic transplantation was 58%. The cumulative incidence of relapse was 29% after allogeneic and 67% after autologous transplantation. The cumulative incidence of non-relapse mortality was 0% after autologous and 12% after allogeneic transplantation. This retrospective single center analysis in a limited number of standard-risk patients clearly demonstrates that early autologous transplantation in first complete remission leads to an acceptable long-term outcome with a short overall treatment duration of less than 6 months compared with more than 2 years with conventional chemotherapy. More sensitive and standardized methods to detect minimal residual disease (MRD) will further help to identify those patients more accurately who are most likely to benefit from such a short and intensive treatment strategy (i.e., MRD negative standard-risk patients) or those who require early targeted therapy (e.g., blinatumomab) in case of MRD positivity. Early allogeneic transplantation results in long-term survival/cure in nearly two-thirds of all high and highest risk, and relapsed/refractory patients.

Background/Aim: Despite multiple treatment options, multiple myeloma (MM) remains an incurable disease with poor outcome. Patients and Methods: We retrospectively analyzed the outcome of MM patients undergoing an allogeneic (allo-SCT; n=34) or autologous stem cell transplantation (auto-SCT; n=41) as salvage treatment for relapsed/refractory (r/r) disease. Results: After a median observation period of 79.9 months in the auto group and 15.7 months in the allo group, the 5- and 10-year OS rates were 54% and 44% in the auto group and 17% and 4% in the allo group (p=0.0002), respectively. The 5- and 10-year disease-free survival in the auto group was 21% and 8%, and 14% and 5% in the allo group (p=0.0142), respectively. The 5- and 10-year cumulative incidence of relapse/progression in the auto group was 69% and 82%, and 64% and 69% in the allo group (p=0.0759), respectively. The 5- and 10-year non-relapse mortality in the auto group was significantly lower than that in the allo group [5% versus 45% (p=0.0001)]. Conclusion: A second autotransplant in selected r/r patients offers an acceptable long-term outcome partly because of the significantly lower treatment-related morbidity and mortality.

T-cell-redirecting therapies have transformed the treatment of relapsed/refractory multiple myeloma (RRMM) but are associated with substantial infection risk. We systematically reviewed infections after CAR T-cell therapy and bispecific antibodies (BsAbs), focusing on incidence, timing, pathogens, risk factors, and prevention. Following PRISMA guidelines, we searched PubMed through May 22, 2026, and included studies reporting infectious outcomes in RRMM patients treated with CAR-T cells or BsAbs. A total of 123 predominantly early-phase, non-comparative studies were analyzed. Across BCMA-directed CAR-T products and BsAbs, infections were frequent (any-grade incidence ~ 40-80%), with highest risk early after CAR-T infusion and during the first months of BsAb therapy. Grade ≥ 3 infections were common and exceeded 50% in several BsAb cohorts. Fatal infections were less frequent but occurred across both CAR-T and BsAb studies. In randomized CAR-T trials, grade 5 infections represented a substantial proportion of treatment-related deaths. Talquetamab showed lower infection rates (47-55%) but relevant mucocutaneous toxicity. Viral and bacterial pathogens predominated; CMV reactivation, invasive fungal infections, and Pneumocystis jirovecii pneumonia, particularly without prophylaxis, were also reported. Risk factors included neutropenia, corticosteroid/tocilizumab exposure, and hypogammaglobulinemia. Antiviral and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and, most notably, immunoglobulin replacement reduced infections, though residual risk persisted. Real-world data suggest higher infection-related healthcare use and mortality with BsAbs versus CAR-T therapy. Extended dosing intervals may reduce infections, particularly severe infections, while preserving efficacy. Infectious toxicity remains a key limitation. Risk is particularly high with BCMA-targeted therapies and continuous BsAb administration. Tailored prophylaxis, early immunoglobulin replacement, and response-adapted treatment strategies, including extended dosing intervals, may improve safety and outcomes.

Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy characterized by proliferation and accumulation of premature lymphoid blasts. Depending on risk factors, the survival of acute lymphoblastic leukemia has significantly improved over the last decades. During the last years, measurable residual disease (MRD) assessment has evolved into one of the most sensitive markers for prognosis and risk of relapse. For this reason, measurable residual disease detection and monitoring count as standard evaluation in patients with acute lymphoblastic leukemia. Allogeneic stem cell transplantation is still the recommended treatment option for patients with high and highest risk profiles as well as for relapsed or refractory settings. The increased understanding of the pathomechanism and heterogeneity of acute lymphoblastic leukemia has led to the development of several novel therapeutic opportunities such as tyrosine-kinase inhibitors, antibody-based therapies and CAR-T cells with the aim of improving clinical outcomes. Furthermore, the major advances in disease understanding of ALL have led to the identification of different subgroups and better disease stratification. Even though novel therapy targets are constantly developed, acute lymphoblastic leukemia remains a challenging and life-threatening disease. To improve the historically unsatisfying result in therapy of adult acute lymphoblastic leukemia many clinical trials have recently been initiated to determine the optimum combination regimens of novel and old agents for adult acute lymphoblastic leukemia.

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of plasma cells. Despite dramatic improvements in patients′ survival over the past decade due to advances in therapy exploiting novel molecular targets (immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies), the treatment of relapsed and refractory disease remains challenging. Recent studies confirmed complex, dynamic, and heterogeneous genomic alterations without unifying gene mutations in MM patients. In the current review, we survey recent therapeutic strategies, as well as molecular profiling data on MM, with emphasis on relapsed and refractory cases. A critical appraisal of novel findings and of their potential therapeutic implications will be discussed in detail, along with the author’s own experiences/views.