High dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) remains the preferred first line consolidation strategy for newly diagnosed multiple myeloma (MM). However, The role of HDT/ASCT in first relapse is uncertain in the context of novel therapies. This study evaluates real-world outcomes of MM patients in first relapse, focusing on the role of consolidative HDT/ASCT.

This retrospective cohort study was conducted at a large tertiary referral center in Northern Netherlands. MM patients who received first-line HDT/ASCT and obtained a good response were included. The time to next treatment or death (TTNT-D 2) and overall survival (OS) were evaluated, while identifying prognostic factors. A landmark analysis was performed at 6 months, including only patients with a partial response (PR) or better after re-induction.

This study identified 237 patients potentially eligible for repeated HDT/ASCT of whom 111 (47%) underwent a second consolidative HDT/ASCT. The median follow-up is 40 months. Baseline characteristics were largely similar, though second HDT/ASCT was applied only after achieving PR or better. In the landmark analysis, absence of high-risk cytogenetics and good performance status were associated with longer TTNT-D 2. Consolidative second HDT/ASCT, absence of high-risk cytogenetics and longer first response duration were associated with longer OS. Transplantation-related mortality rate was < 1%.

This study highlights the viability of second HDT/ASCT as treatment option for relapsed MM, particularly for patients with good responses to first-line HDT/ASCT. In the era of novel agents, second HDT/ASCT should be considered a feasible and effective consolidative strategy.

Minimal residual disease (MRD) evaluation is a recognized endpoint in clinical trials. Both next-generation flow and sequencing could be used as complementary techniques to detect myeloma cells after therapy to measure the depth of response and novel drug efficacy. Anti-CD38 monoclonal antibodies combined with proteasome inhibitors and immunomodulatory drugs have increased the quality of response in myeloma patients, and MRD evaluation is also entering routine clinical practice in many hematological centers. This review analyzes updated results from recent clinical trials utilizing anti-CD38 monoclonal antibodies such as isatuximab and daratumumab in terms of their responses and MRD data. MRD-driven therapy appears promising for the future of MM patients, and emerging minimally invasive techniques to assess MRD are under investigation as novel potential methods to replace or integrate traditional MRD evaluation.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

To explore the correlation between immune status, genetic profile, laboratory parameters, and staging in patients with newly diagnosed multiple myeloma (NDMM) and to investigate the clinical characteristics of these patients along with their associated risk factors. The clinical data of 135 patients with multiple myeloma (MM) admitted to the First Affiliated Hospital of Guangxi Medical University between March 2020 and December 2023 were retrospectively collected. These data were systematically organized to evaluate the staging status of patients, including the Durie-Salmon, International Staging System, Revised International Staging System, and mSMART 3.0 staging systems. Additionally, the study included analysis of peripheral blood T-lymphocyte subpopulations and Fluorescence In Situ Hybridization results. Laboratory indices were collected at the initial diagnosis of patients with MM prior to any treatment. These data were subsequently analyzed to ascertain their significance in staging patients with multiple myeloma. Among 135 patients with MM, N-terminal pro-brain natriuretic peptide (NT-proBNP) and lambda light chain (λ light chain) levels were higher in patients with abnormal kidney function (P < .05). NT-proBNP and λ light chain levels can predict abnormal renal function in patients with NDMM. The λ light chain levels were significantly higher in Zhuang patients than in Han patients (P < .05). Patients with high staging differed in total T cell percentages, CD8+ cell percentages, T cells, CD3+/CD4-/CD8- double-negative cell percentages, CD8+T cells, age, NT-proBNP, and M protein levels (P < .05). In addition, M protein levels and age were positively correlated with CD4+T cells and negatively correlated with CD8+T cells (P < .05). CD8+ T cells, age, NT-proBNP, M protein level, and cytogenetic abnormalities represent distinct aspects of immune status, tumor load, and cytogenetic status at the initial diagnosis of patients. These indices are closely associated with the clinical stage of patients and can be combined to assess the clinical stage of multiple myeloma patients after admission to the hospital. Additionally, NT-proBNP and λ light chain levels play a role in predicting abnormal renal function in patients with NDMM.

Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)-negative status in patients with a complete response.

A total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; P<0.001). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P = 0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P = 0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups.

Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. (Funded by Sanofi and a Cancer Center Support Grant; IMROZ ClinicalTrials.gov number, NCT03319667.).

Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells (PCs) in the bone marrow and recurrent cytogenetic abnormalities. The incidence of MM worldwide is on the rise. 1q21+ has been found in ~30-40% of newly diagnosed MM (NDMM) patients.1q21+ is associated with the pathophysiological mechanisms of disease progression and drug resistance in MM. In the present review, the pathogenesis and clinicopathological features of MM patients with 1q21+ were studied, the key data of 1q21+ on the prognosis of MM patients were summarized, and the clinical treatment significance of MM patients with 1q21+ was clarified, in order to provide reference for clinicians to develop treatment strategies targeting 1q21+.

Cytogenetic karyotypes such as t(4; 14), del(17p), t(14; 16), t(14; 20), and TP53 mutations are associated with high-risk multiple-myeloma (MM) and indicate poor prognosis. Therefore, cytogenetic testing is extremely important for determining prognosis of MM. However, the aberrant karyotypes reported in the current literature are incomplete. The cytogenetic karyotype 17p gain has not received widespread attention, and its relationship with MM prognosis is unknown; additionally, the prognosis of 17p gain associated with t(4; 14) has not been studied in depth. Therefore, we introduce a special case in which a patient had both 17p gain and t(4; 14). An 81-year-old woman was admitted to the Affiliated Hospital of Shandong University of Traditional Chinese Medicine for stomach discomfort. The patient had no relevant medical history. Laboratory tests, immunophenotyping, and haematological results suggested MM, and cytogenetic tests indicated 17p gain and t(4; 14) with no other abnormalities. She was treated with two different chemotherapeutic regimens and achieved very good partial response, but eventually experienced biochemical relapses after discontinuing therapy. However, she eventually achieved good disease control with a bortezomib, lenalidomide, and dexamethasone-based regimen; she has survived longer than 5 years, much longer than the 1 year reported for MM patients with t(4:14), and been progression-free more than 3 years. We use this case to explore the possible relationship between the 17p gain and prognosis of patients with MM, as well as the treatment of MM with high-risk cytogenetic karyotypes. This case enriches the clinical application of cytogenetic analysis and adds important indicators for the prognosis of MM patients.

This study involves the collation and analysis of clinical characteristics and laboratory findings in patients with multiple myeloma (MM) combined with renal insufficiency. The objective was to assess the impact of various treatment methods on patient outcomes and the incidence of adverse events in individuals with MM and renal insufficiency.

We analyzed the correlation between clinical characteristics, gene loci, fluorescence in situ hybridization, treatment methods, and prognosis in patients with MM and renal insufficiency. The differences in hematological and therapeutic efficacy indexes between two groups subjected to different treatments were evaluated. The assessment of treatment effectiveness was based on the total effective rate, calculated as the sum of stringent CR rate, complete remission rate, very good partial remission rate, and partial remission rate.

(1) The renal insufficiency group exhibited higher percentages of bone marrow abnormal plasma cells, lactate dehydrogenase (LDH), blood calcium, white blood cell count, percentage of neutrophils, and blood β2-microglobulin (β2-MG) levels compared to the normal renal function group. Conversely, hemoglobin levels and lymphocyte percentage were lower in the renal insufficiency group. Binary logistic regression analysis identified hemoglobin, blood calcium values, blood β2-MG, and LDH as independent risk factors for the development of renal insufficiency in patients with MM (p < 0.05). (2) Based on the Durie-Salmon staging criteria, the proportion of Stage III patients was the highest (up to 81.8%), indicating that patients with MM usually suffer from insidious disease, often with high tumor load and late-disease stage at the time of consultation. International Staging System (ISS) and Revised ISS staging also revealed a higher proportion of Stage III patients in the renal insufficiency group (p < 0.05), indicating a worse long-term prognosis in patients with MM and renal insufficiency. (3) Before treatment, there was no significant difference between the two groups in the analysis of various indices. Complications such as sepsis, herpes zoster, peripheral neuropathy, thrombosis, secondary pulmonary infection, and cardiac complications were significantly lower in the BCD group (Bortezomib + Cyclophosphamide + Dexamethasone) compared to the BD group (Bortezomib + Dexamethasone) (χ2 = 6.333, p < 0.05), suggesting fewer complications with the BCD regimen. (4) The clinical treatment effects analysis indicated that the BCD group demonstrated a more significant impact than the BD group in the treatment of MM.

The application of the BCD regimen in the treatment of MM has shown significant efficiency, effectively alleviating clinical symptoms with fewer adverse reactions and high safety.

Anti-CD38 targeting has become an important pillar of the treatment for patients with multiple myeloma (MM). This evolution was spearheaded by daratumumab, but more recently isatuximab became the second CD38-directed monoclonal antibody to receive EMA approval for the treatment of patients with relapsed/refractory (RR) MM. In recent years, real-world studies have become increasingly important to confirm and solidify the clinical potential of novel anti-myeloma therapies.

This article describes the real-world experience with isatuximab-based therapy in a selection of four RRMM patients treated with an isatuximab-based treatment regimen in the Grand Duchy of Luxembourg.

Three of the four cases described in this article consist of heavily pretreated patients who were previously exposed to daratumumab-based therapy. Interestingly, the isatuximab-based therapy provided clinical benefit to all three of these patients illustrating that prior exposure to an anti-CD38 mAb does not preclude a response to isatuximab. As such, these findings further support the design of larger prospective studies looking into the impact of prior daratumumab use on the efficacy of isatuximab-based therapy. In addition, two of the cases included in this report displayed renal insufficiency and the experience with isatuximab in these patients further supports the use of this agent in this setting.

the clinical cases described illustrate the clinical potential of isatuximab-based treatment for RRMM patient in a real-world setting.

Overall outcomes for multiple myeloma have improved due to the availability of new therapies, but patients with relapsed/refractory multiple myeloma harbouring certain factors continue to pose a therapeutic challenge. These challenging features include high-risk cytogenetics, renal impairment, patient characteristics such as age and frailty, and extramedullary disease. Prior refractory status and number of prior lines add further complexity to the treatment of these patients. While newer regimens are available and have suggested efficacy in these patient populations through subgroup analyses, differences in trial definitions and cut-offs make meaningful comparisons difficult. This review aims to examine the available clinical trial data for patients with high-risk cytogenetics, renal impairment, age and frailty and extramedullary disease.

CD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved-daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites.

Among the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38-mediated T-cell activation. Patients who respond to anti-CD38 targeting treatment experience more marked changes in T-cell expansion, activity, and clonality than nonresponders.

Resistance mechanisms that undermine the immunomodulatory effects of CD38-targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment-related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T-cell engagers.

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Multiple new drugs have been approved over the past 5 years for the treatment of relapsed/refractory multiple myeloma (RRMM), and these are being increasingly widely used. Clinicians need to familiarize themselves with common toxicities associated with these drugs and with novel toxicities requiring specific management and supportive care.

We review common toxicities associated with agents approved for RRMM in the past 5 years, including the anti-CD38 monoclonal antibody isatuximab, the antibody-drug conjugate belantamab mafodotin, the bispecific antibody teclistamab, the chimeric antigen receptor (CAR) T cell products idecabtagene vicleucel and ciltacabtagene autoleucel, the selective inhibitor of nuclear export compound selinexor, and the drug-peptide conjugate melflufen, as well as toxicities associated with emerging agents for RRMM including additional bispecific antibodies, the BCL-2 inhibitor venetoclax, and the cereblon E3 ligase modulators iberdomide and mezigdomide. We searched the published literature using PubMed, plus congress abstracts, for the above list of drug names or classes and 'myeloma.'

Optimal management of toxicities associated with these recently approved and emerging therapies will be critical in maximizing clinical benefit and aiding widespread adoption in routine clinical practice. We summarize current recommendations and guidelines and provide expert insights into supportive care requirements.