Background: Belantamab mafodotin (belamaf) is a BCMA-targeting antibody–drug conjugate used in triple-class refractory multiple myeloma. Despite its efficacy, keratopathy remains a significant dose-limiting toxicity. Following its withdrawal from the U.S. market in 2022, its use in Austria is limited to clinical trials or compassionate use. Methods: In this real-world, retrospective study, we analyzed 36 relapsed/refractory, BCMA-naïve multiple myeloma patients treated at the University Hospital of Vienna (January 2020–June 2024); 42% received a reduced dose (1.9 mg/kg) throughout all treatment cycles. The primary objective was to assess adverse events, particularly keratopathy, and the impact of dose modifications on toxicity and efficacy. Results: The overall response rate was 64%, with responders having significantly fewer prior therapy lines (median 3 vs. 4.5, p = 0.015). Median PFS was 7.3 months, significantly longer in responders (11.1 vs. 1.6 months, p < 0.0001); median OS was 20.1 months, also longer in responders (not reached vs. 18 months, p = 0.031). Keratopathy occurred in 75% of patients; 33% experienced grade 3–4 events. Dose reduction significantly decreased grade 3–4 keratopathy (7% vs. 52%, p = 0.004) and thrombocytopenia (33% vs. 67%, p = 0.048) without compromising efficacy. Conclusions: Belamaf dose reductions improved tolerability without loss of efficacy, supporting reduced dosing in practice.

Summary: The 64th annual meeting was held in New Orleans, Louisiana from December 10–13, 2022. More than 150 abstracts concerning multiple myeloma have been presented, mirroring the rapid progression, and deepening of our understanding of this disease.Evolution in treatment options includes new therapeutic regimens incorporating established drugs as well as entirely newly discovered substances, targeting malignant plasma cells utilizing the power of the immune system. In the following, a personal shortcut of hot topics is presented, focusing on data from large clinical trials which have the potency to change clinical practice as well as on new treatment options which may impact future strategies to achieve deep and durable responses aiming to pave the way to potential cure.

Key Points: Kidney involvement in patients with multiple myeloma has many different findings in kidney histology. Persistent dialysis requirement is a major cause of mortality. The rapid initiation of modern myeloma therapy is essential to prevent the need for dialysis and reduce mortality. Background: Acute or CKD affects 20%–40% of patients with multiple myeloma (MM). While the negative prognostic effect of kidney involvement is established, the specific effect of different histological patterns remains poorly understood. We aimed to characterize the clinical outcomes associated with distinct kidney histologies in patients with MM. Methods: We retrospectively analyzed 193 patients with MM who underwent kidney biopsy, comparing outcomes with 62 patients with MM without kidney disease. Patients were categorized by histological findings: cast nephropathy (CN, n =120), lightchain (AL) amyloidosis ( n =19), monoclonal Ig deposition disease (MIDD, n =8), and other renal disease ( n =46). We evaluated kidney function, dialysis requirements, treatment responses, and survival across histological subtypes and treatment modalities (conventional therapy versus modern agents including proteasome inhibitors, CD38 antibodies, and autologous stem cell transplantation). Results: The CN and MIDD groups had the lowest median eGFR at biopsy (13.0 and 25.5 ml/min per 1.73 m ² , respectively). Nephrotic-range proteinuria (>3.5 g/24 hours per Kidney Disease Improving Global Outcomes) was observed in the AL amyloidosis group (median 3910 mg/24 hours). KRT was initiated in 42.5% of patients. The proportion achieving KRT independence was 42.4% in the CN group and 50% in the other renal disease group, whereas none in the AL amyloidosis or MIDD groups recovered sufficient native kidney function. Modern combination therapy significantly improved renal outcomes, with 100% of patients receiving triple therapy showing renal response. KRT dependency was the strongest predictor of mortality: Patients remaining on KRT had significantly shorter survival compared with those never requiring KRT (12.7 versus 56.2 months, P < 0.001). The extent of improvement in kidney function did not influence survival; only dialysis status was prognostically relevant. Conclusions: Kidney histology determines distinct clinical trajectories in patients with MM, with CN showing potential for dialysis reversibility. Modern combination therapies significantly improve renal outcomes. The requirement for ongoing KRT was the primary predictor of overall survival.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with drug-refractory acute myeloid (AML) or acute lymphoblastic leukemia (ALL). Patients and Methods: We retrospectively analyzed 82 patients (median age 47.5 years, range 19–69; female:male ratio 1:1.28) with drug-refractory (R) or relapsed/refractory (RR) acute leukemia (AML n = 66; ALL n = 16) who were treated with clofarabine (10 mg/m²) and cyclophosphamide (200 mg/m²) days 1–4 (ClofCy) prior to HSCT. Results: ClofCy resulted in rapid cytoreduction (median time to granulocytes <0.5 × 10⁹/L: 5 days). HSCT was performed in 62.2% (51/82) of our patients. Infections (18/31, 58%) were the main reason to withhold transplantation. HSCT and non-HSCT patients differed significantly regarding the median number of chemotherapies received prior to ClofCy (HSCT, median = two therapies; non-HSCT, median = three therapies; p = 0.027). Median overall survival (OS) was 0.31 years in all patients (5- and 10-year OS; 24% and 20%, respectively). HSCT patients had a median OS of 1.23 years (5- and 10-year OS; 38.4% and 31%, respectively) and those in the non-HSCT cohort a median OS of 0.11 years (5-year OS; 0%). Median OS and relapse-free survival (RFS) in the HSCT patient cohort were 1.04 and 0.9 years, respectively. Acute graft-versus-host disease (aGvHD) was associated with inferior survival (median OS 0.46 years), whereas chronic graft-versus-host disease (cGvHD) was associated with improved OS and RFS (above 50%). Conclusion: ClofCy is an effective bridging regimen enabling HSCT in patients with R/RR acute leukemia. Introducing ClofCy may improve the probability of reaching HSCT and long-term survival in this cohort of patients with poor prognosis.

Summary: B‐cell maturation antigen‐directed chimeric antigen receptor (CAR) T cells have revolutionized the treatment of relapsed/refractory multiple myeloma. However, no randomized head‐to‐head comparison of idecabtagene vicleucel (ide‐cel) and ciltacabtagene autoleucel (cilta‐cel) is available, and real‐world data suggest differences in efficacy and toxicity. We performed a nationwide retrospective real‐world analysis (RWA) of Austrian patients treated with ide‐cel or cilta‐cel between January 2024 and July 2025. Ninety patients were included, with largely balanced baseline characteristics and frequent high‐risk features. Bridging therapy was administered to 94.4% of patients, resulting in high response rates prior to lymphodepletion. After a median follow‐up of 17.6 months, no early separation of the progression‐free survival (PFS) curves was observed between CAR‐T products. Multivariable analyses showed a trend towards improved PFS with cilta‐cel, whereas true extra‐medullary disease (EMD) and prior bispecific antibody treatment before T‐cell apheresis were associated with inferior PFS. Although previous RWA have demonstrated an early divergence in PFS between cilta‐cel and ide‐cel, this pattern was not observed in our cohort. The high effectiveness of bridging therapy may have contributed to these findings. Our results support further investigation of optimal bridging strategies and treatment sequencing while highlighting the persistent unmet need of patients with true EMD.