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OBJECTIVES: Circular RNA_0003489 (Circ_0003489) promotes multiple myeloma (MM) progression and bortezomib resistance in MM cells, while its potential as a biomarker in newly diagnosed MM (NDMM) patients is unclear. Thus, this study aimed to investigate the association of circ_0003489 expression with treatment response and survival in NDMM patients who received bortezomib-based induction therapy. METHODS: Bone marrow (BM) specimens from 85 NDMM patients at diagnosis or before treatment and from 15 donor controls during BM examination were retrieved in this retrospective study. Circ_0003489 derived from BM plasma cells was detected by reverse transcription-quantitative polymerase chain reaction and cut by quartile and median for further analysis. RESULTS: Circ_0003489 expression was increased in NDMM patients versus donor controls (P < 0.001). Circ_0003489 quartile was positively correlated with BM plasma cells (P = 0.040), international staging system (ISS) stage (P = 0.007), the revision of ISS stage (P = 0.003), beta-2-microglobulin (P = 0.011), and lactate dehydrogenase (P = 0.042) in NDMM patients. Increased circ_0003489 quartile was linked with a lower possibility of achieving complete response (P = 0.020) and partial response or better (P = 0.041) in NDMM patients. Elevated circ_0003489 expression cut by quartile (P = 0.020) and cut by median (P = 0.006) were linked with decreased progression-free survival (PFS) in NDMM patients. Increased circ_0003489 expression cut by median was associated with shortened overall survival (OS) in NDMM patients (P = 0.038). Meanwhile, higher circ_0003489 quartile independently forecasted poorer PFS (hazard ratio = 1.342, P = 0.045), but not OS in NDMM patients. CONCLUSION: Circ_0003489 expression is increased and reflects unfavorable treatment response and survival in NDMM patients who receive bortezomib-based induction therapy.

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OBJECTIVE: To investigate the role of plasma circulating cell-free DNA (cf-DNA) in the screening and diagnosis of patients with newly diagnosed multiple myeloma (MM) and explore the changes of cf-DNA in terms of content and integrality in the assessment of disease in patients treated with chemotherapy. METHODS: Peripheral blood specimens were collected from 35 newly diagnosed MM patients and 18 healthy volunteers, and 13 of the 35 patients who had finished 3 courses of standard induction chemotherapy were selected as follow-up group. The ALU247 and ALU115 fragments were used as the target genes, and the cf-DNA content in the plasma of patients and healthy controls was measured by quantitative polymerase chain reaction (qPCR). The integrality of cf-DNA was calculated by the ratio of ALU247 to ALU115. RESULTS: Both the concentration of ALU247 and ALU115 fragments and the integrality of cf-DNA in patients were significantly higher than those in healthy controls (all P < 0.05). Patients who had underwent 3 courses of induction chemotherapy had significantly decreased concentration of ALU247 and ALU115 fragments and integrality of cf-DNA after treatment (all P < 0.05), and strong positive correlations were manifested between cf-DNA integrality and serum M protein content, as well as proportion of abnormal plasma cells in bone marrow before and after treatment (r =0.703, 0.705). CONCLUSIONS: Cf-DNA has certain positive significance for the screening and diagnosis of MM. Furthermore, cf-DNA may be a synergism or alternative to serum M-protein content and proportion of abnormal plasma cells in bone marrow in assessing the condition, curative effect and prognosis of patients.

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Small extracellular vesicles (EVs) play a pivotal role in intercellular communication across various physiological and pathological contexts. Despite their growing significance as disease biomarkers and therapeutic targets in biomedical research, the lack of reliable isolation techniques remains challenging. This study characterizes vesicles that were isolated from conditioned culture media (CCM) sourced from three myeloma cell lines (MM.1S, ANBL-6, and ALMC-1), and from the plasma of healthy donors and multiple myeloma patients. We compared the efficacy, reproducibility, and specificity of isolating small EVs using sucrose cushion ultracentrifugation (sUC) vs. ultrafiltration combined with size-exclusion chromatography (UF-SEC). Our results demonstrate that UF-SEC emerges as a more practical, efficient, and consistent method for EV isolation, outperforming sUC in the yield of EV recovery and exhibiting lower variability. Additionally, the comparison of EV characteristics among the three myeloma cell lines revealed distinct biomarker profiles. Finally, our results suggest that HBS associated with Tween 20 improves EV recovery and preservation over PBS. Standardization of small EV isolation methods is imperative, and our comparative evaluation represents a significant step toward achieving this goal.

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Background: The second most common hematologic cancer worldwide is multiple myeloma (MM), with incidence and mortality rates that have more than doubled over the past 30 years. The safety and efficacy of daratumumab regimens in the treatment of newly diagnosed MM (NDMM) is demonstrated in clinical trials. Objective: To assess the financial effects of the adoption of subcutaneous daratumumab (dara-SC) rather than intravenous daratumumab (dara-IV) for the treatment of NDMM in three Gulf countries (Qatar, Oman and the United Arab Emirates; UAE), a cost-minimization model was constructed. Methods: We performed static cost minimization analyses from a societal perspective to evaluate the costs and possible reductions in resource utilization associated with a shift from dara-IV infusion to dara-SC injection for NDMM patients over a 5-year time horizon. The model included 2 scenarios: the current scenario in which 100% of patients with NDMM are treated with dara-IV infusion and a future scenario in which dara-SC injection is gradually adopted over the modeled time horizon. The model differentiated precisely between autologous stem cell transplantation (ASCT)-eligible and ASCT-ineligible NDMM patients in terms of their number in each group and the associated therapeutic regimens. One-way sensitivity analyses were also conducted. Results: The model showed that the use of dara-SC in NDMM patients who were eligible or ineligible for ASCT resulted in lower non-drug costs, including premedication drug costs, adverse-effect costs, administration costs, medical staff costs, and indirect costs. The resulting total savings over the 5-year time horizon of the model for Hamad Medical Corporation, Sultan Qaboos University Hospital/Royal Hospital, Sheikh Shakhbout Medical City (SSMC), and Tawam Hospital were QAR -2 522 686, OMR -143 214, AED -30 010 627, and AED -5 003 471, respectively. Conclusion: The introduction of dara-SC as a front-line treatment for NDMM patients in Qatar (Hamad Medical Corporation), Oman (Sultan Qaboos University Hospital, Royal Hospital-MOH), and the UAE (SSMC and Tawam Hospital) can help save resources and minimize constraints on the healthcare system.

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Aim: Obtain clinical consensus on factors impacting first-line prescribing for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Materials & methods: A double-blinded, modified Delphi panel was employed. USA-based hematologists/oncologists who treat TIE patients with NDMM were selected as expert panelists. Results: Consensus was reached that patient frailty, performance status, comorbidities, treatment efficacy, and adverse event profile affect first-line prescribing. All panelists agreed it is important to use the most efficacious treatment first; 88% of panelists considered daratumumab-containing regimens the most efficacious. Panelists agreed treatment should be continued until progression while benefits outweigh risk. Conclusion: Findings reinforce the importance of using the most efficacious regimen upfront for TIE NDMM, and nearly all panelists considered daratumumab-containing regimens the most efficacious treatment.

The purpose of this study was to determine the latest clinician preferences and opinions on factors affecting initial treatment selection for people recently diagnosed with multiple myeloma and unable to receive a bone marrow transplant, and to understand challenges with current treatments used in clinical practice. A panel of doctors with an average of two decades of experience treating blood disorders and cancers were recruited as expert panelists. Experts discussed treatment options by completing two rounds of surveys on treatment and one round of discussion. All experts agreed that the most effective treatment should be used first. Most experts considered treatment containing the drug daratumumab to be the most effective. Experts agreed that treatment should be continued until the cancer worsens if the treatment offers more benefits than side effects.

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INTRODUCTION: Ciltacabtagene autoleucel (cilta-cel), a BCMA-targeting CAR-T therapy, is approved in the United States and Europe for patients with relapsed/refractory multiple myeloma (RRMM) and ≥1 prior line of therapy (LOT), including a proteasome inhibitor and an immunomodulatory drug, and are lenalidomide refractory. AREAS COVERED: We examine recent long-term data in heavily pretreated RRMM (LEGEND-2, CARTITUDE-1) and earlier LOTs (CARTITUDE-4) compared with standard therapy and discuss the rationale for investigating cilta-cel as frontline therapy for transplant-eligible and transplant-ineligible patients (CARTITUDE-5, CARTITUDE-6). EXPERT OPINION: CAR-T therapies can improve outcomes for patients with MM across different LOTs. CARTITUDE-1 and CARTITUDE-4 have set a new bar for efficacy, with median PFS of 34.9 months in heavily pretreated patients (CARTITUDE-1) and a 74% relative risk reduction for progression/death versus standard care in patients with 1-3 prior LOTs (CARTITUDE-4), with manageable safety. Response rates were consistent between the two studies: 98% in CARTITUDE-1 and approaching 100% for infused patients in CARTITUDE-4. Cilta-cel could be a key treatment choice for patients with RRMM after first LOT. Clinical trials investigating frontline cilta-cel therapy will provide valuable insights into optimizing treatment pathways with the aim to potentially cure MM.

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Introduction Multiple myeloma (MM) is a hematological disorder characterized by aberrant multiplication of malignant plasma cells in the bone marrow. The current mainstay of treatment for patients with newly diagnosed MM (NDMM) is a triplet regimen with a proteasome inhibitor, immunomodulatory imide, and dexamethasone. The two most common of these triplet regimens are VLD (bortezomib/lenalidomide/dexamethasone) and VCD (bortezomib/cyclophosphamide/dexamethasone). This study aims to compare the outcomes between these two therapies in transplant-ineligible patients with NDMM. Methods We conducted a retrospective study at the Aga Khan University Hospital in Karachi, Pakistan. All NDMM transplant-ineligible patients either receiving VLD or VCD therapy between January 2015 and December 2022 were included in our study. Hematological parameters before and after treatment were obtained from hospital records. Response to treatment was classified according to the International Myeloma Working Group (IMWG) response criteria as either complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), or progressive disease (PD). The response to treatment as well as overall survival (OS) and progression-free survival (PFS) was compared between VCD and VLD therapy. A p-value of 0.05 or less was taken to be statistically significant. Results Twenty (23.8%) patients in the VCD group and 20 (23.0%) in the VLD group underwent complete remission. Seven (8.3%) patients experienced disease progression in the VCD group, while the figure stood at three (3.4%) in the VLD group. There was no statistically significant difference in the overall response rate between the VCD (58; 69.0%) and VLD (70; 80.5%) groups (p=0.086), a difference that was not statistically significant on the Chi-square test. OS was comparable between VCD (69.1 months, 95%CI: 61.3-77.0) and VLD (76.9 months, 95%CI: 69.0-85.0) therapies. Conclusions The study did not identify any statistically significant distinction in the treatment outcomes between the VCD and VLD regimens among NDMM patients ineligible for transplantation. Nevertheless, the study highlights the positive outcomes observed with both treatments in this specific patient cohort. This implies that either regimen could be deemed suitable as a treatment option for patients in low- and middle-income countries. Since both regimens demonstrate comparable effectiveness, assessing the cost-effectiveness of these regimens is crucial. Future research should also explore the economic aspects of the two treatment options.

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Chimeric antigen receptor (CAR) T cell therapy has revolutionized the management of relapsed and refractory myeloma, with excellent outcomes and a tolerable safety profile. High dose chemotherapy with autologous hematopoietic stem cell transplantation (AHCT) is established as a mainstream of newly diagnosed multiple myeloma (NDMM) management in patients who are young and fit enough to tolerate such intensity. This standard was developed based on randomized trials comparing AHCT to chemotherapy in the era prior to novel agents. More recently, larger studies have primarily shown a progression free survival (PFS) benefit of upfront AHCT, rather than overall survival (OS) benefit. There is debate about the significance of this lack of OS, acknowledging the potential confounders of the chronic nature of the disease, study design and competing harms and benefits of exposure to AHCT. Indeed upfront AHCT may not be as uniquely beneficial as we once thought, and is not without risk. New quadruple-agent regimens are highly active and effective in achieving a deep response as quantified by measurable residual disease (MRD). The high dose chemotherapy administered with AHCT imposes a burden of short and long-term adverse effects, which may alter the disease course and patient's ability to tolerate future therapies. Some high-risk subgroups may have a more valuable benefit from AHCT, though still ultimately suffer poor outcomes. When compared to the outcomes of CAR T cell therapy, the question of whether AHCT can or indeed should be deferred has become an important topic in the field. Deferring AHCT may be a personalized decision in patients who achieve MRD negativity, which is now well established as a key prognostic factor for PFS and OS. Reserving or re-administering AHCT at relapse is feasible in many cases and holds the promise of resetting the T cell compartment and opening up options for immune reengagement. It is likely that personalized MRD-guided decision making will shape how we sequence in the future, though more studies are required to delineate when this is safe and appropriate.

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The introduction of daratumumab has improved treatment outcomes for multiple myeloma (MM). However, infectious complications are a concern in patients receiving daratumumab. Although some reports have explored the association between daratumumab and cytomegalovirus (CMV) infection, most of these have focused on relapsed or refractory cases, and few describe patients with newly diagnosed MM (NDMM). In this study, we retrospectively analyzed CMV infections in 53 patients with NDMM who received daratumumab as induction therapy. CMV infection was defined as CMV antigenemia positivity. The median age at treatment initiation was 71 years (range, 50-82 years), and 50.9% of the patients were female. The median duration of daratumumab administration was 10.0 months (range, 0.3-63.8 months). Nine patients developed CMV infection, and the cumulative incidence rate at six months was 18.1% (95% confidence interval: 8.9-30.1%). One patient experienced CMV retinitis and required antiviral therapy, while the remaining eight patients did not require treatment and could be managed through observation. Few cases of CMV infection during daratumumab treatment for NDMM required treatment. However, the incidence of CMV infection was not negligible, suggesting that regular monitoring for CMV is worth considering to ensure more appropriate management during daratumumab treatment.

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INTRODUCTION: Daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd) are commonly used treatment combinations for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). D-Rd and VRd demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naïve comparisons of efficacy across the two trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas SWOG S0777 enrolled both TIE patients and transplant-eligible patients who chose to defer/refuse frontline stem cell transplantation (median age 63 years). The present study compared progression-free survival (PFS) in TIE patients with NDMM treated with D-Rd versus VRd based on an adjusted indirect treatment comparison (ITC) that leveraged individual patient-level data from MAIA and SWOG S0777. METHODS: Harmonized inclusion/exclusion criteria (including age ≥ 65 years as a proxy for transplant ineligibility) and propensity-score weighting were used to balance the trial populations on measured baseline characteristics. After differences in trial populations were adjusted for, an anchored ITC was performed wherein within-trial PFS hazard ratios (HRs) for D-Rd versus Rd and VRd versus Rd were estimated and used to make indirect inference about PFS for D-Rd versus VRd. RESULTS: PFS HRs were 0.52 (95% confidence interval [CI] 0.41-0.67) for D-Rd versus Rd based on MAIA data, 0.88 (95% CI 0.63-1.23) for VRd versus Rd based on SWOG S0777 data, and 0.59 (95% CI 0.39-0.90) for the Rd-anchored ITC of D-Rd versus VRd. Sensitivity and subgroup analyses produced results consistent with the primary results. CONCLUSION: This anchored ITC demonstrated a greater PFS benefit for D-Rd versus VRd in TIE patients with NDMM. In the absence of head-to-head trials comparing D-Rd and VRd, the present trial may help inform treatment selection in this patient population.

Multiple drug combinations can be used to treat patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for a stem cell transplant. Two of these combinations­daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd)­have each been studied in clinical trials (MAIA and SWOG S0777) against the combination of lenalidomide plus dexamethasone (Rd), but D-Rd and VRd have not been compared directly in a head-to-head clinical trial. Our study used data from the MAIA and SWOG S0777 trials to indirectly compare outcomes observed with D-Rd and VRd. For this indirect comparison between D-Rd and VRd, we first made adjustments to the patient populations of each trial to make them more similar to each other; this helped to make sure any differences we saw in treatment outcomes between D-Rd and VRd would not be because of differences in the characteristics of the patients who participated in the trials. After we made these adjustments to the patient populations of each trial, both D-Rd and VRd lowered the risk of disease progression or death compared with Rd alone. However, when indirectly compared in our study, D-Rd lowered the risk of disease progression or death by 41% compared with VRd. As data directly comparing treatment outcomes for D-Rd and VRd are not available, this indirect comparison can contribute to the information used to make treatment decisions for patients with NDMM who are not eligible for a stem cell transplant.

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BACKGROUND: Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified. PATIENTS: We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022. RESULTS: The overall response rate was 82% for patients with 1q21+and 78% for patients without 1q21+. Median progression-free survival (PFS) and median overall survival (OS) were not reached in either group. Neither 1q21 copy number nor co-existence of other high-risk cytogenetic abnormalities significantly affected PFS or OS. CONCLUSION: Our preliminary data suggests that outcomes of daratumumab treatment in NDMM 1q21+patients might be non-inferior to those in non-1q21+patients.

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Isatuximab-based combinations are among the accepted standard-of-care regimens for early-line treatment of patients with relapsed/refractory multiple myeloma (RRMM), based on the results of the Phase 3 ICARIA-MM and IKEMA trials. Further study findings have shown benefit with Isa-based combinations in patients with newly diagnosed MM, as reported from the randomized GMMG-HD7 and CONCEPT trials. Isa is currently approved in various countries for intravenous (IV) administration in patients with RRMM. A more convenient route of administration, such as subcutaneous (SC) injection, and faster IV infusion may substantially increase convenience of treatment. In this review, we outline evidence emerging from clinical trials that shows increasing clinical applicability of Isa across the MM therapeutic spectrum. We then review recent study results demonstrating that new treatment modalities, either SC Isa administration via an on-body delivery system (OBDS) or fast, 30-minute, fixed-volume IV infusion, are safe and effective, and enhance convenience of treatment with Isa for MM patients and healthcare providers. In the recently reported Phase 1b study, the safety profile and efficacy of Isa administered SC plus pomalidomide-dexamethasone were comparable to those observed with Isa administered IV plus pomalidomide-dexamethasone in the control arm and in the ICARIA-MM trial. Analysis of patient-reported outcomes indicated patient confidence in SC Isa administration and satisfaction with treatment delivery by OBDS. These findings point to SC administration as the preferred route for future treatment with Isa-based combinations, as well as to the use of fast, 30-minute IV infusions in settings where SC administration of Isa might not be available.

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BACKGROUND: Multiple myeloma is the third most common hematologic malignancy in Malaysia. The introduction of novel agents over the past decades has improved patient outcome and survival substantially. However, these agents incur significant economic burden, thus leading to limited use in less developed countries. This study aims to report on the real-world treatment pattern and outcome of newly diagnosed multiple myeloma (NDMM) patients from a resource-constraint setting. METHODS: This is a retrospective study on NDMM patients diagnosed between 1 January 2008 and 31 December 2022 in a single academic center. Patients' demographic and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS). RESULTS: One hundred and thirty-six NDMM patients with a median age of 64.0 years (ranged from 38 to 87 years old) were included. Bortezomib-containing regimens were the most commonly used induction agent, followed by thalidomide. Almost half of the patients (47.1%) achieved very good partial response (VGPR) or complete remission (CR), while 31.6% achieved partial response (PR). Bortezomib containing regimen was associated with significantly deeper and more rapid response, (p=0.001 and p=0.017, respectively) when compared to other agents. Only 22.8% of these patients proceeded to upfront autologous haematopoietic stem cell transplantation.  The median OS and PFS were 60.0 months and 25.0 months, respectively. Best initial response and upfront autologous stem cell transplantation (ASCT) were significantly associated with better PFS. CONCLUSION: Achieving at least a VGPR significantly associated with better outcome in NDMM patients. In a resource constrain country, we recommend incorporating bortezomib in the induction therapy followed with an upfront ASCT.

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Biochemical evolution of serum IgG-Kappa monoclonal component during the first line with VRD (x1), DARA-VRD (x4), and the second line with ISA-KD (x4).

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BACKGROUND: Infection, a significant cause of death in multiple myeloma (MM) patients, is a common complication and is closely associated with immunoparesis. There exists no clear definition of early infection, so early infection is defined in this paper as the occurrence within 3 months after diagnosis, considering the high incidence of infections within 3 months after diagnosis. This study established a new nomogram model based on immunoparesis to identify MM patients with high-risk early infection. METHODS: A retrospective collection of 430 NDMM patients from June 2013 to June 2022 was conducted, and the patients were further divided into a training cohort and a validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) was used to select the best variables that can be used to establish a new nomogram prediction model. Validation was performed in the validation and entire cohorts. RESULTS: After diagnosis, 67.7 % of the patients suffered from severe infection within 1 year, and 59.5 % experienced the first severe infection within 3 months. Variables associated with an increased risk of severe infection in the first 3 months included: BMPC, D-dimer, serum ß2 microglobulin, immunoparesis, albumin, and eGFR. The nomogram based on the above six factors achieved a good C-index of 0.754, 0.73, and 0.731 in predicting early infection in the training cohort, validation cohort, and entire cohort, respectively. Finally, the time-dependent receiver operating characteristic (ROC) curve and decision curve analysis (DCA) of the nomogram showed that the model provided superior diagnostic capacity and clinical net benefit. CONCLUSION: In this study, we established a nomogram model to predict early grade ≥ 3 infection in NDMM patients. This model can assist clinicians in identifying NDMM patients with high-risk infections and improve their prognosis through early intervention.

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OBJECTIVE: To investigate the correlation of peripheral blood platelet/lymphocyte ratio (PLR) with Treg and Th17 and its influence on prognosis in newly diagnosed multiple myeloma (MM). METHODS: One hundred thirty-five newly diagnosed multiple myeloma patients admitted to the Department of Hematology of Zhengzhou People's Hospital from June 2015 to October 2022 were selected as MM group. Clinical data included sex, age, immune typing, ISS stage, blood calcium (Ca), albumin (ALB), hemoglobin (Hb), PLR, LDH, ß2 microglobulin (ß2-MG), Treg and Th17 levels. Sixty healthy volunteers who underwent physical examination in our hospital during the same period were selected as the control group. PLR, Treg and Th17 levels in MM group and control group were compared. Pearson was used to analyze the correlation between PLR and Treg, Th17. The relationship between MM patients with different PLR and clinical features and prognosis was analyzed. RESULTS: The PLR and Th17 of MM patients were significantly higher than that of control group, and Treg was significantly lower than that of control group (P<0.05). In MM patients, PLR was negatively correlated with Treg (r=-0.616), and PLR was positively correlated with Th17 (r=0.555). Using mean PLR=132.72 as the boundary, 135 MM patients were divided into high PLR group (n=54) and low PLR group (n=81). In MM patients with high PLR, ISS stage, ALB and Treg were significantly higher than those in low PLR group, while Th17 was significantly lower than those in low PLR group (P<0.05). By univariate and COX regression analysis, PLR was an independent prognostic risk factor for newly diagnosed MM patients (P<0.05). MM patients with high PLR had better PFS and OS, and the difference was statistically significant compared with MM patients with low PLR (P<0.05). 65 patients admitted from June 2015 to December 2018 were used as the training set, and 70 patients admitted from January 2019 to October 2022 were used as the validation set. The OS of MM patients with different PLR were compared respectively. The results showed that the conclusions of the training set and the validation set were consistent. PLR with high expression had higher OS (P<0.01). CONCLUSION: PLR is correlated with Treg and Th17 in newly diagnosed MM patients, and high PLR has better prognosis. PLR can be used to evaluate the prognosis of MM patients.

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Concurrent polycythemia vera with newly diagnosed multiple myeloma is extremely rare. We described a 70-year-old woman with concurrent polycythemia vera and newly diagnosed multiple myeloma. Genetic testing confirmed the JAK2 V617F mutation for the first time, while determination of serum erythropoietin decreased. A retrospective review of our patient's case was conducted thereafter, and related literature was systemically reviewed. We totally identified eight cases with concurrent polycythemia vera with newly diagnosed multiple myeloma, which were further analyzed and compared. The present case is the first patient of newly diagnosed multiple myeloma with diagnosis of polycythemia vera confirmed by positive JAK2 V617F mutation. Abnormal erythremia, hepatosplenomegaly and thrombosis history suggested comorbidity of polycythemia vera with newly diagnosed multiple myeloma. The bortezomib-based chemotherapy regimen seemed to be effective on controlling the proliferation of erythrocyte. Whereas the pathogenesis of these two entities remains to be further investigated.

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INTRODUCTION: The prevalence of multiple myeloma (MM) has gradually increased over the last few decades in India due to growing population, better disease awareness, and improved diagnostic procedures. Despite such advances, MM remains an incurable and relapsing disease due to its heterogeneity and genomic instability. With the inclusion of monoclonal antibodies, especially daratumumab in the frontline regimen, the management landscape of MM has improved significantly resulting in better disease control and patient outcomes. AREAS COVERED: This review aims to provide an in-depth summary of efficacy and safety of frontline daratumumab therapy in treatment of MM including patients with high-risk cytogenetic profile. EXPERT OPINION: Based on the review of literature, daratumumab in frontline therapy has demonstrated improved efficacy in terms of reduction in disease progression or death, and superior minimal residual disease (MRD)-negativity rates with an acceptable safety profile in patients with newly diagnosed MM (NDMM) including patients with high-risk cytogenetic profile. Daratumumab alone or in combination with other drugs has shown similar clinical outcomes in patients with relapsed/refractory MM. Hence, daratumumab can be used upfront in patients with MM.

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Background: Limited data are available on the concordance between multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for minimal residual disease (MRD) detection in a large trial for multiple myeloma (MM) patients. Methods: MRD was explored in the FORTE trial for transplant-eligible MM patients randomised to three carfilzomib-based induction-intensification-consolidation treatments and carfilzomib-lenalidomide (KR) vs R maintenance. MRD was assessed by 8-colour 2nd-generation flow cytometry in patients with ≥very good partial response before maintenance. NGS was performed in case of suspected complete response (CR) in a correlative subanalysis. Biological/prognostic concordance between MFC and NGS, conversion to MRD negativity during maintenance, and 1-year/2-year sustained MRD negativity were explored. Findings: Between September 28, 2015 and December 22, 2021, 2020 samples were available for MFC and 728 for the simultaneous MFC/NGS correlation in the "suspected CR population". Median follow-up was 62 months. Biological agreement was 87% at the 10-5 and 83% at the 10-6 cut-offs. A remarkable prognostic concordance was observed: hazard ratios in MFC-MRD and NGS-MRD-negative vs -positive patients were 0.29 and 0.27 for progression-free survival (PFS) and 0.35 and 0.31 for overall survival, respectively (p < 0.05). During maintenance, 4-year PFS was 91% and 97% in 1-year sustained MFC-MRD-negative and NGS-MRD-negative patients (10-5), respectively, and 99% and 97% in 2-year sustained MFC-MRD-negative and NGS-MRD-negative patients, regardless of treatment received. The conversion rate from pre-maintenance MRD positivity to negativity during maintenance was significantly higher with KR vs R both by MFC (46% vs 30%, p = 0.046) and NGS (56% vs 30%, p = 0.046). Interpretation: The significant biological/clinical concordance between MFC and NGS at the same sensitivity suggests their possible use in the evaluation of one of the currently strongest predictors of outcome. Funding: Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.

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Background: 18F-FDG-PET/CT is the current standard technique to define minimal residual disease (MRD) outside the bone marrow (BM) in multiple myeloma (MM), recently standardised applying the Deauville scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) and defining the complete metabolic response (CMR) as uptake below the liver background (DS <4). Methods: In this analysis, we aimed at confirming the role of CMR, and complementarity with BM multiparameter flow cytometry (MFC) at 10-5, in an independent cohort of newly diagnosed transplant-eligible MM patients previously enrolled in the phase II randomised FORTE trial. 109 of the 474 global patients enrolled in the trial between February 23, 2015, and April 5, 2017, who had paired PET/CT (performed at baseline [B] and preceding maintenance therapy [PM]) and MFC evaluation, were included in this analysis. Findings: At B, 93% of patients had focal lesions within the bones (FS ≥4 in 89%) and 99% increased BM uptake (BMS ≥4 in 61%). At PM, CMR was achieved in 63% of patients, which was a strong predictor for prolonged PFS in univariate analysis at landmark time PM (HR 0.40, P = 0.0065) and in Cox multivariate analysis (HR 0.31, P = 0.0023). Regarding OS, a trend in favour of CMR was present in univariate (HR 0.44, P = 0.094), and Cox multivariate model (HR 0.17, P = 0.0037). Patients achieving both PET/CT CMR and MFC negativity at PM showed significantly extended PFS in univariate (HR 0.45, P = 0.020) and multivariate analysis (HR 0.41, P = 0.015). Interpretation: We herein confirm the applicability and validity of DS criteria to define CMR and its prognostic relevance and complementarity with MFC at the BM level. Funding: Amgen, Celgene/Bristol Myers Squibb, Italian Ministry of Health (RC-2022-2773423).