Myeloma Research Articles

MRD-driven phase 2 study of daratumumab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma

In newly diagnosed multiple myeloma (NDMM), measurable residual disease (MRD) status is prognostically important, but its role in treatment decisions remains unclear. In a phase 2 trial, we assessed daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) induction followed by a next-generation sequencing-based MRD-adapted strategy. The primary outcome was complete response (CR) and stringent CR (≥CR) after induction. Flow cytometry was used to profile T cells. Among 39 patients, 21 (54%) achieved ≥CR after induction (P=.375), with MRD-negative rates of 59% (10-5) and 41% (10-6). Patients who were MRD-negative (n=24, group A) received lenalidomide maintenance, showing sustained MRD negativity in 14 of 18 (77.8%) for ≥12 cycles. MRD-positive transplant-eligible patients (n=8, group B) underwent autologous stem cell transplantation, with 62.5% converting to MRD-negative at 10-5 (37.5% at 10-6) posttransplant. MRD-positive, transplant-ineligible patients (n=4, group C) received KRd consolidation. Best MRD-negative rates improved to 77% (10-5) and 72% (10-6). No new safety concerns were identified for Dara-KRd. With a median follow-up of 30.1months, 3, 2, and 1 patient(s) in groups A, B, and C, respectively, have progressed or died. We observed that Dara-KRd strongly activated memory T cells, which was associated with an MRD-negative state post induction. Although the primary outcome was not met, Dara-KRd induction in NDMM achieved high ≥CR and MRD-negative rates without new safety concerns. The post induction MRD-adapted strategy deepened responses in MRD-positive patients and maintained durable MRD control in MRD-negative patients. This trial was registered at www.clinicaltrials.gov as #NCT04113018.

Second-line anti-CD38 monoclonal antibody therapy mitigates the negative impact of functional high-risk status in myeloma patients.

In multiple myeloma, functional high risk (FHR) is a predictor of poor outcomes. It is defined as M protein reduction to ≤ 50% of normal, suboptimal response (SR), or progressive disease (PD) within 12months (i.e., early PD). The clinical significance of anti-CD38 monoclonal antibody (MoAb) as second-line treatment for FHR myeloma remains unclear. We retrospectively investigated the efficacy of anti-CD38 MoAb as second-line treatment for FHR myeloma. We included 332 patients who were newly diagnosed with myeloma and received proteasome inhibitors and/or immunomodulatory drugs as first-line therapy. Their median age was 70years, and 29.4% were FHR. At a median follow-up of 48.5months, the overall survival (OS) in the FHR group was significantly shorter (hazard ratio [HR], 2.086; P < 0.001). However, the OS in the SR without early-PD group was comparable to that in the non-FHR group (HR, 1.659; P = 0.330). The OS in patients with FHR who received anti-CD38 MoAb as second-line treatment was similar to that in the non-FHR group (HR, 1.157; P = 0.660). Anti-CD38 MoAb as second-line treatment improved the outcome in our patients with FHR although FHR predicted a poor prognosis.

An evaluation of linvoseltamab for treatment of relapsed/refractory multiple myeloma.

Bispecific antibody therapies, primarily targeting B-cell maturation antigen (BCMA), have shown remarkable outcomes in the treatment of heavily pretreated patients with multiple myeloma (MM). However, there are no current head-to-head trials informing practice for selection or sequencing of optimal T cell redirection strategies in later lines of therapy. Linvoseltamab is a novel BCMA-targeted bispecific antibody that was recently evaluated in the phase 1/2 LINKER-MM1 trial and is currently pending formal regulatory approval. In this drug evaluation, we review efficacy and toxicity profiles of linvoseltamab in the context of currently approved bispecific antibody therapies for MM. Specifically, we highlight differences in dosing strategy, cytokine release syndrome (CRS) kinetics, and indirect efficacy comparisons between trials of linvoseltamab and other bispecific antibodies. Linvoseltamab has a similar efficacy profile with favorable CRS incidence and time-to-onset compared to other approved bispecific antibodies. Pending final regulatory approval and labeling, further real-world analyses are needed to evaluate its final role in the evolving landscape of T cell redirection therapy for MM.

Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of myeloma cells and accumulation of genetic lesions. MM progression is accompanied by increased aggressiveness and drug resistance. Even the goal of "cure" remains hard to reach for most patients, advances in diagnosis and treatment have allowed some to achieve durable remissions and transition to plateau phase. Single-cell sequencing, with its powerful ability to analyze cellular heterogeneity and molecular patterns at ground-breaking resolution, is informative for deciphering tumors and their microenvironment. In this review, we summarize the new insights of studies facilitated by emerging single-cell sequencing into clonal evolution, myeloma-supported microenvironment transformation, epigenetic changes, and novel prognostic and therapeutic strategies for MM, revealing the key mechanisms underlying MM progression and the direction of future efforts. With the continuous expansion of the research scope and optimization of related technologies, single-cell sequencing is expected to revolutionize our understanding of the biology and evolutionary dynamics of MM and contribute to the radical and precise improvement of treatment.

Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow-confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary natural killer and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.

Recovery from acute kidney injury treated with dialysis in patients with multiple myeloma treated with proteasome inhibitors.

Recovery from acute kidney injury treated with dialysis in patients with multiple myeloma treated with proteasome inhibitors.

Bortezomib, thalidomide, and dexamethasone versus thalidomide and dexamethasone for response rates in multiple myeloma patients: a retrospective study

Bortezomib, thalidomide, and dexamethasone versus thalidomide and dexamethasone for response rates in multiple myeloma patients: a retrospective study

Myeloma cell-derived CXCL7 facilitates proliferation of tumor cells and occurrence of osteolytic lesions through JAK/STAT3 pathway

Osteolytic lesions and pathological fractures are hallmark manifestations of multiple myeloma (MM), profoundly influencing the quality of life and self-care ability of MM patients. By analyzing transcriptome data and single-cell RNA-seq data from our center and the GEO database, a subset of MM cells with high expression levels of chemokine CXCL7 was identified. This subset of MM cells possesses a high capacity for proliferation and activation of osteoclast signaling pathway. CXCL7 might be a crucial regulator of osteolytic damage in MM. Subsequently, the association between the expression level of CXCL7 and pathological fractures in patients was investigated, and the impact of CXCL7 on MM proliferation was confirmed both in vivo and in vitro. A mouse xenograft tumor model was established through intravenous injection of myeloma cell lines based on the homing ability of plasma cells. Moreover, the mechanism by which CXCL7 promotes the activation of osteoclast signaling pathways in MM was explored. Our findings reveal that elevated CXCL7 levels significantly enhance MM cell proliferation, increasing the risk of pathological fractures in MM patients. Additionally, our mouse xenograft tumor model demonstrated that CXCL7 can induce femoral fractures and reduce bone mineral density. Concurrently, it was discovered that CXCL7 could activate the JAK/STAT3 pathway via CXCR2 and upregulate the expression levels of MMP13 and C-myc, facilitating MM cell proliferation and activation of the osteoclast signaling pathway. Our study offers novel insights into the pathogenic mechanism of osteolytic lesions and implies that targeting CXCL7 may present a new therapeutic avenue for MM.

Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis

BackgroundMultiple myeloma (MM) is the most aggressive and prevalent primary malignant tumor within the blood system, and can be classified into grades RISS-I, II, and III. High-grade tumors are associated with decreased survival rates and increased recurrence rates. To better understand metabolic disorders and expand the potential targets for MM, we conducted large-scale untargeted metabolomics on plasma samples from MM patients and healthy controls (HC).MethodsOur study included 33 HC, 38 newly diagnosed MM patients (NDMM) categorized into three RISS grades (grade I: n = 5; grade II: n = 19; grade III: n = 8), and 92 MM patients post-targeted therapy with bortezomib-based regimens. Simultaneously, MM cell lines were employed for validation studies. Metabolites were analyzed and identified using ultra high liquid chromatography coupled with Q Orbitrap mass spectrometry (UPLC-HRMS), followed by verification through a self-built database.ResultsCompared with HC participants, a total of 70 metabolites were identified as undergoing significant changes in NDMM. These metabolites were significantly enriched in citrate cycle, choline metabolism, glycerophospholipid metabolism, and sphingolipid metabolism, etc. Notably, a panel of circulating plasma metabolite biomarkers, including lactic acid and leucine, has emerged not only as diagnostic indicators but also as valuable tools for tumor surveillance, aiding in the assessment of disease stage and prognostic evaluation. Moreover, 14 differential metabolites were identified in both MM cell lines and MM patients. Among these, intracellular levels of lactate and leucine significantly decreased in vitro, aligning with the plasma results.ConclusionOur findings on key metabolites and metabolic pathways provide novel insights into the exploration of diagnostic and therapeutic targets for MM. A prospective study is essential to validate these discoveries for future MM patient care.

Is t(11;14) in newly diagnosed multiple myeloma a favorable outcome in the novel agent era?

Backgroundt(11;14) is considered a standard risk factor in multiple myeloma (MM). However, recent studies suggested that its impact in the context of novel agents remained controversial.MethodsThis retrospective analysis examined the clinical profiles of 375 newly diagnosed patients with MM and compared the outcomes between those with t(11;14) and those with normal cytogenetics.ResultsThe median progression-free survival (PFS) of the 84 patients with t(11;14) was 36 months (95% confidence interval (CI), 23.5–48.5), which was significantly shorter than the median PFS of 65 months (95% CI, 23.0–107.0) for the 59 patients with normal cytogenetics (p = 0.011). Median overall survival (OS) was not reached in either group (p = 0.977). When combined with 1q21 + , t(11;14) showed a trend toward poorer PFS (median PFS: 36 vs. 65 months; p = 0.130). In the presence of high-risk cytogenetics (HRCAs), t(11;14) was associated with a worse PFS (median PFS: 9 vs. 38 months, p = 0.015) and a trend toward shorter OS (median OS: 33 vs. 49 months, p = 0.096). Multivariate analysis indicated that t(11;14) was a poor prognostic factor for PFS. 1q21 + was a detrimental prognostic factor, particularly in the t(11;14) group. Autologous stem cell transplantation (ASCT) may be a beneficial treatment option for patients with t(11;14).ConclusionIn this study, patients with MM with t(11;14) demonstrated poorer PFS than those with normal cytogenetics. Further investigations are required to evaluate the impact of t(11;14) in patients newly diagnosed with MM in the era of novel agents.

Safety assessment of selinexor: a real-world pharmacovigilance study

ABSTRACT Background Selinexor is approved for the treatment of relapsed or refractory multiple myeloma. However, a comprehensive understanding of adverse events associated with selinexor is lacking. Methods Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data of the US Food and Drug Administration Adverse Event Reporting System (FAERS). The disproportionality analysis was conducted. Four algorithms were employed to evaluate the signals of adverse events. The adverse effects of selinexor combined with dexamethasone were compared with bortezomib and dexamethasone. Sensitivity analysis was performed to exclude consumer-reported adverse events. The onset of adverse reactions were calculated. Results A total of 1,698 reports related with selinexor from FAERS were identified. 6 significant system organ class and 42 significant preferred terms (PTs) were found. Unexpected significant adverse events including mania, acute kidney injury, orthostatic hypotension, and embolisms were identified. 14 PTs reported significant signals in treatment of selinexor combined dexamethasone compared with traditional treatment of bortezomib and dexamethasone. 45.2% of adverse events occurred within the first month of starting selinexor. Conclusions Comprehensive analyses of selinexor related adverse events are helpful for clinical detection of adverse events and timely intervention, advancing selinexor’s therapeutic progress in future treatment.

Nontuberculous mycobacterial infections following teclistamab in multiple myeloma.

Not available.

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53

SummaryMalignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case of a T-cell lymphoma harboring a lentiviral integration in a known tumor suppressor, TP53, which developed in a patient with multiple myeloma after B-cell maturation antigen (BCMA) CAR T-cell therapy.

Targeting Caseinolytic Mitochondrial Matrix Peptidase, a Novel Contributor to High-risk Behavior, in Multiple Myeloma.

Plasma cell dyscrasias encompass a spectrum from the precursors monoclonal gammopathy of undetermined significance and smoldering myeloma to symptomatic myeloma, but the genes that enable progression and confer poor prognosis are incompletely understood. Using single cell transcriptomics, we identified the Caseinolytic protease proteolytic subunit (CLPP), a key component of the mitochondrial CLP serine endopeptidase, as being over-expressed in CD138+ neoplastic versus normal, and in symptomatic versus precursor plasma cells. Its high expression was associated with an adverse prognosis across multiple molecularly defined subgroups in the newly diagnosed and relapsed/refractory settings, and with extramedullary disease. Pharmacologic CLPP inhibition and genetic suppression reduced organoid growth, cell viability, and cell cycle progression, while triggering an unfolded protein response and apoptosis. This occurred in association with mitochondrial transmembrane potential loss, and caspase and proteasome activation in a reactive oxygen species-dependent manner. Downstream consequences included autophagy and mitophagy induction, and reductions in oxidative phosphorylation and glycolysis with consequent compromise of mitochondrial and cytoplasmic ATP production. CLP endopeptidase inhibition overcame conventional and novel drug resistance, induced apoptosis in primary samples, showed efficacy in vivo, and could be achieved with the clinically relevant agent inobrodib. Finally, regimens combining a CLPP and proteasome inhibitor showed enhanced efficacy, as did combinations with inhibitors of intermediary metabolism and autophagy. Taken together, our data indicate that CLPP is a key contributor to transformed plasma cells, a novel mediator of high-risk behavior, and a legitimate target for myeloma therapy whose inhibitors could be rationally combined with current therapeutics to improve outcomes.

Bortezomib, thalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone in transplant-eligible newly diagnosed multiple myeloma: a systemic review and meta-analysis

ABSTRACT Background The current study aimed to compare treatment responses, the incidence of the need for auto-HSCT, and the occurrence of specific adverse events (AEs) between VTD and velcade, VRD induction regimens in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM). Methods This systematic review and meta-analysis included 15 studies: six evaluating the VTD regimen and nine evaluating the VRD one. The primary endpoints were response rates after induction therapy and the incidence of a need for autologous hematopoietic stem cell transplantion (auto-HSCT) between the groups. We also examined the occurrence of grade 3 or 4 hematological, infection, and thrombotic AEs in both groups. Results The VTD group showed an overall response rate (ORR) of 93%, while the VRD group had an ORR of 86%. The very good partial response (VGPR) rates were 61% in the VTD group and 60% in the VRD one. The auto-HSCT rate was higher in the VTD group, averaging 93% compared to 70% in the VRD one. The incidence of grade 3 or 4 hematological AEs was 31% for VTD and 33% for VRD. The rates of grade 3 or 4 infection-related AEs were 9% in the VTD group and 14% in the VRD one. The incidence of grade 3 or 4 thrombotic AEs was 4% for VTD and 3% for VRD. Conclusions With comparable safety profiles, VTD and VRD induction therapies are similarly effective for transplant-eligible NDMM, showing similar ORRs and VGPR rates.

The Evolving Landscape in Multiple Myeloma: From Risk Stratification to T Cell-Directed Advanced Therapies

Multiple myeloma is biologically and clinically a complex and heterogeneous disease which develops late in life, with the median age at the time of initial diagnosis being 66 years. In 1975, Durie and Salmon developed the first broadly adopted staging system in multiple myeloma, and in the ensuing decades, the risk stratification tools have improved and now incorporate different parameters to better predict the prognosis and to guide the treatment decisions. The International Staging System (ISS) was initially developed in 2005, revised in 2015 (R-ISS), and again in 2022 (R2-ISS). Tremendous progress has been achieved in multiple myeloma therapy over the past 25 years with the approval of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, resulting in a major paradigm shift. The dysfunction of the innate and adaptive immune system, especially in the T cell repertoire, represents a hallmark of multiple myeloma evolution over time, supporting the need for additional therapeutic approaches to activate the host’s immune system and to overcome the immunosuppressive tumor microenvironment. Novel T cell-directed therapies include chimeric antigen receptor (CAR) T cell therapies and bispecific antibodies that leverage the immune system’s T cells to recognize and attack the tumor cells. Second-generation anti-BCMA CAR T cell therapies and bispecific antibodies that bind the tumor antigen BCMA or GPRC5D onto myeloma cells and CD3 on the T cell’s surface are currently available for the treatment of relapsed/refractory multiple myeloma. Despite impressive results obtained with currently approved treatments, multiple myeloma remains incurable, and almost all patients eventually relapse. Moreover, patients with extramedullary disease and plasma cell leukemia represent an unmet medical need that require additional strategies to improve the outcome. In this review, we provide an overview of the evolution of risk stratification and the treatment of multiple myeloma.

Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention

Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members. Notably, the re-introduction of BIM into resistant cells restored VTX sensitivity and synergized with MCL-1 inhibitors. Upstream signaling pathways, including growth factor receptor tyrosine kinase (RTK) and phosphoinositide-3-kinase (PI3K) were implicated in this dysregulation. Simultaneous inhibition of MCL-1, BCL-XL, and upstream PI3K, RTK (FGF, EGF, and IGF1) mediated signaling enhanced VTX sensitivity. Post-translational modifications of MCL-1, particularly its stabilization via acetylation and phosphorylation, were investigated, although their inhibition only marginally increased VTX sensitivity. Lastly, the inhibition of AURKA and mitochondrial respiration also improved VTX sensitivity in some resistant HMCLs. Our findings suggest that combining VTX with MCL-1 and BCL-XL inhibitors or PIK3/RTK inhibitors holds potential for overcoming resistance. The study illustrates the importance of understanding molecular determinants of resistance to develop tailored therapeutic strategies.

Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study.

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10-5 by next-generation sequencing. Major secondary endpoints included complete response (CR) or better (≥CR) rate, progression-free survival and sustained MRD-negativity rate at 10-5. At a median follow-up of 58.7 months, the MRD-negativity rate was 60.9% with D-VRd versus 39.4% with VRd (odds ratio, 2.37; 95% confidence interval (CI), 1.58-3.55; P < 0.0001). Rates of ≥CR (81.2% versus 61.6%; P < 0.0001) and sustained MRD negativity (≥12 months; 48.7% versus 26.3%; P < 0.0001) were significantly higher with D-VRd versus VRd. Risk of progression or death was 43% lower for D-VRd versus VRd (hazard ratio, 0.57; 95% CI, 0.41-0.79; P = 0.0005). Adverse events were consistent with the known safety profiles for daratumumab and VRd. Combining daratumumab with VRd produced deeper and more durable MRD responses versus VRd alone. The present study supports D-VRd quadruplet therapy as a new standard of care for transplant-ineligible or transplant-deferred NDMM. ClinicalTrials.gov registration: NCT03652064 .

Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma.

BCMA-targeted CAR T-cells transformed the treatment of relapsed and refractory multiple myeloma (RRMM), yet improvements are needed in manufacturing, toxicity and efficacy. We conducted a phase 1 clinical trial of BMS-986354, an autologous BCMA CAR T manufactured using an optimized NEX-T® process, in participants with triple-class exposed, RRMM. The 65 participants had a median of 5 (range 3-13) prior regimens, 39% had cytogenetic high-risk, 91% triple-class refractory, and 43% extra-medullar disease. Part A (dose-escalation) of the study enrolled participants in cohorts receiving 20 (N = 7), 40 (N = 24), or 80 (N = 11)x 106 CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×106 CAR + T cells. Across dose levels, cytokine release syndrome (CRS) occurred in 82% (2% grade ≥3), neurotoxicity in 8% (2% grade ≥3), and infections in 32% of participants (5% grade ≥ 3). The response rate was 95%, with 46% achieving complete responses. Median progression-free survival was 12.3 months (95% CI 11.3-16). Compared to orvacabtagene autoleucel (same CAR construct, conventional manufacturing), BMS-986354 had higher proportion of T central memory cells, were less differentiated and had enhanced potency and proliferative capacity, supporting the use of NEX-T® in future CAR T development.

Real-world outcomes of maintenance therapy post-autologous stem cell transplantation in newly diagnosed multiple myeloma

BackgroundIn the Republic of Korea, only lenalidomide, bortezomib, ixazomib, and thalidomide monotherapy are available as maintenance therapy post-autologous stem cell transplantation (ASCT).MethodsTo determine whether maintenance therapy confers a survival benefit in the real world, we compared treatment outcomes according to the use and type of maintenance therapy in patients who underwent ASCT following frontline therapy with the triplet regimen of bortezomib, thalidomide, and dexamethasone for newly diagnosed multiple myeloma in 15 nationwide centers.ResultsA total of 512 patients were analyzed (no-maintenance group, n = 359, and maintenance group, n = 153 patients). Among those receiving maintenance therapy, 104 (68%) received thalidomide, 33 (21%) lenalidomide, and 16 (10%) bortezomib or ixazomib. The median progression-free survival (PFS) from the time of ASCT was 26.4 and 44.1 months in the no-maintenance and maintenance groups, respectively. In the multivariate analysis, the use of maintenance therapy was significantly associated with better PFS. After adjustment for the type and duration of maintenance therapy, the use of bortezomib or ixazomib was associated with better PFS than other drugs. Longer duration of therapy was associated with improved PFS. No statistically significant difference was observed in overall survival and secondary malignancy rates by use or type of maintenance.ConclusionDespite practical limitations, maintenance therapy after ASCT demonstrated a gain in PFS in the real world, and there was no clear increase in the risk of secondary malignancy. Therefore, it may be prudent to consider implementing maintenance therapy in a feasible manner.