Background: Renal impairment is a frequent and severe complication of multiple myeloma, most commonly caused by light-chain cast nephropathy. Therapeutic plasma exchange (TPE) has been proposed as an adjunctive approach to rapidly reduce circulating free light chains; however, its clinical benefit remains controversial. Methods: We retrospectively analyzed 71 patients treated between 2013 and 2023, of whom 30 received TPE in addition to anti-myeloma therapy and 41 received anti-myeloma therapy alone. Renal outcomes were assessed within a predefined early treatment window encompassing the first 4–6 cycles of therapy. Renal response was defined as a ≥50% reduction in serum creatinine and/or dialysis independence. Multivariable logistic regression and sensitivity analyses were performed to adjust for baseline imbalances, including renal function and anti-myeloma backbone therapy. Results: Although renal function improved significantly over time in both groups, renal response rates were comparable between patients treated with and without TPE (40% vs. 36.6%). In multivariable analysis, TPE was not independently associated with renal response. Importantly, in a sensitivity analyses restricted to patients receiving bortezomib-based regimens, the addition of TPE remained unassociated with improved renal outcomes. Conclusions: In this real-world cohort, adjunctive TPE did not confer a significant advantage in renal recovery or dialysis independence beyond contemporary anti-myeloma therapy. These findings indicate that renal recovery is predominantly driven by effective anti-myeloma treatment rather than extracorporeal light-chain removal.

Multiple myeloma (MM) treatment becomes a major challenge once triple-class or penta-refractoriness develops. Emerging immunotherapies, including bispecific antibodies or chimeric antigen receptor (CAR)-T cell therapy, are promising options for such patients. However, the requirement for specialized expertise and staff under stringent manufacturing conditions results in high costs and restricted production. This article explores the manufacturing and clinical application of CAR T-cells in MM, highlighting their potential, limitations, and strategies to enhance efficacy. CAR-T can be manufactured by pharmaceutical companies or accredited academic centers authorized to produce and market gene-edited cellular products. This process includes sequential steps: T cell apheresis from the patient, selection of the cells, activation, gene transfer, expansion of the produced cells, cryopreservation, and reinfusion of the cells into a lymphodepleted patient. While CD3+ T cells are typically employed for CAR-T production in clinical studies, studies have demonstrated the potential advantages of specific T cell subgroups, such as naive, central memory, and memory stem cells, in enhancing efficacy. Following T cell harvesting, the subsequent phase involves genetic modification. CAR-T cells are frequently produced by applying viral vectors such as γ-retrovirus or lentivirus. Although viral vectors are commonly used, non-viral methods-including CRISPR/Cas9 and integrative mRNA transfection methods produced by transposons-are also employed. Five different CAR-T cell generations have been developed. The myeloma-specific targets B-cell maturation antigen (BCMA), signaling lymphocyte activation molecular family 7, and G protein-coupled receptor class C group 5 member D are the most extensively studied in clinical trials. Emerging CAR-T cell targets under investigation include CD138, CD19, kappa light chain, CD56, NY-ESO-1, CD70, TACI, and natural killer G2D. In 2021, idecabtagene vicleucel, a BCMA-targeting agent, became the first CAR-T therapy approved for relapsed/refractory MM, marking a significant milestone in MM treatment. Subsequently, ciltacabtagene autoleucel has also been approved. However, CAR-T resistance is an emerging issue. Resistance mechanisms include T cell exhaustion, antigen escape (loss of BCMA), and tumor microenvironment-related inhibitors. To address these challenges, strategies such as BCMA non-targeted or dual-targeted CAR-T, memory T cells, humanized CAR-T, and rapidly manufactured PHE885 cells have been developed. To enhance specificity, ongoing investigations include bicistronic CAR/co-stimulator receptors, formation of memory-phenotype T cells, combination with immunomodulators or checkpoint inhibitors, armored CAR-T cells, cancer-associated fibroblast inhibitors, and CAR approaches that inhibit exhaustion signals. In conclusion, studies are exploring the use of CAR-T at an earlier stage, including at diagnosis, with an aim to replace ASCT. CAR-T has introduced a new dimension to MM treatment; however, limited efficacy in high-risk MM and the emergence of resistance to CAR-T remain key challenges to be addressed.

The purpose of this study was to assess dermatological lesions in hematologic malignancy patients. Patient file records pertaining to patients diagnosed with hematologic malignancies and followed up in our center between 2019 and 2024 will be retrospectively examined for demographic information, hematologic disease diagnoses, clinical features, dermatological examination data obtained with dermatology consultation, pathology results of biopsies taken from skin lesions, and the presence of other malignancies. The study comprised 241 participants with hematologic malignancies. The male to female ratio was 1.3, and the median age was 64. Acute myeloid leukemia (AML) accounted for 24.1% of diagnoses, while multiple myeloma (MM) came in second with 18.3%. With a rate of 14.9%, dermatitis was the most frequent form of lesion, followed by drug response (14.5%). In the AML group, dermatitis and fungal infection were the most frequent lesions, while in the MM group, medication reactions were more common. Patients with malignancy experienced urticaria considerably more frequently (p=0.004). At the time of lesion development, 81.7% of the patients were receiving chemotherapy, with alkylating drugs being the most frequently utilized agents (24.9%). Twenty percent of individuals who had biopsies reported having vasculitis and drug-related dermatological responses. 98.8% of the patients received local/topical supportive treatments without stopping systemic treatment. According to this study, dermatological lesions in hematologic malignancies may be connected to the course of the disease as well as treatment. These results imply that routine follow-up for hematologic patients should include a dermatological evaluation.

Despite PFS in MM patients extending to 17 years due to contemporary quadruplet induction therapies, there remains a necessity for novel products in the treatment of high-risk patients. BCMA, GPRC5D, FcRH5, SLAMF7, and TACI represent the principal CAR-T target molecules, with dual-targeted treatments under development to enhance their efficacy. Ide-cel and Cilta-cel are CAR-T cells directed against BCMA, having received FDA approval for RRMM based on the Phase 2 KarMMa and CARTITUDE trials, respectively. Research is currently being conducted on the administration of these products in newly diagnosed patients and for maintenance therapy. Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in-vivo proliferation capability, are regarded as very efficacious. Arlo-cel, developed for the significant target GPRC5D, has demonstrated efficacy against conventional treatments. The development of academic CAR-Ts such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness. The real-world data have demonstrated comparable efficacy and safety outcomes in both academic and commercial CAR-T research. CAR-T cell researchs are also being undertaken in SMM and AL amyloidosis. CAR-PRISMM and CAR-HiRiSMM are regarded as extremely effective and safe for patients with high-risk SMM. NXC-201, which targets BCMA, has been developed for AL amyloidosis. Notwithstanding these promising outcomes, numerous difficulties confront CAR-T therapy. These factors may relate to the tumor, the patient, and the CAR-T product. To overcome these issues, strategies are being implemented, including combination therapy, the incorporation of gamma-secretase inhibitors etc. In conclusion, CAR-T treatments have evolved into an effective therapy modality being anticipated to be utilized in earlier phases in the future. Gene editing (CRISPR) method contributes to the future perspective.