Management Of Multiple Myeloma Patients Research Articles

Construction of immune-related gene pairs signature to predict the overall survival of multiple myeloma patients based on whole bone marrow gene expression profiling.

Multiple myeloma (MM) is a plasma cell dyscrasia that is characterized by the uncontrolled proliferation of malignant PCs in the bone marrow. Due to immunotherapy, attention has returned to the immune system in MM, and it appears necessary to identify biomarkers in this area. In this study, we created a prognostic model for MM using immune-related gene pairs (IRGPs), with the advantage that it is not affected by technical bias. After retrieving microarray data of MM patients, bioinformatics analyses like COX regression and least absolute shrinkage and selection operator (LASSO) were used to construct the signature. Then its prognostic value is assessed via time-dependent receiver operating characteristic (ROC) and the Kaplan-Meier (KM) analysis. We also used XCELL to examine the status of immune cell infiltration among MM patients. 6-IRGP signatures were developed and proved to predict MM prognosis with a P-value of 0.001 in the KM analysis. Moreover, the risk score was significantly associated with clinicopathological characteristics and was an independent prognostic factor. Of note, the combination of age and β2-microglobulin with risk score could improve the accuracy of determining patients' prognosis with the values of the area under the curve (AUC) of 0.73 in 5 years ROC curves. Our model was also associated with the distribution of immune cells. This novel signature, either alone or in combination with age and β2-microglobulin, showed a good prognostic predictive value and might be used to guide the management of MM patients in clinical practice.

Clinical utility of 7-probe FISH panel in multiple myeloma in a resource-constrained setting: A retrospective and prospective observational study

ABSTRACT Background: A 7-probe fluorescence in situ hybridization (FISH) panel identifying abnormalities such as immunoglobulin heavy chain (IGH) rearrangement, deletion 17p (TP53 – tumor protein 53), hyperdiploidy, and amplification of 1q, t(11;14), t(14;16), and t(4;14) aids in diagnosis and treatment planning for patients with multiple myeloma, particularly for high-risk patients and short-survival rates. Objectives: The primary objective of the study was to stratify patients with multiple myeloma based on the risk of developing the disease. The secondary objective was to assess the frequency of triple- and double-hit myeloma. Materials and Methods: This retrospective and prospective observational study was conducted in the Department of Cytogenetics, Amrita Institute of Medical Science, Kochi, Kerala, India from January 2020 to September 2022. Bone marrow samples were analyzed using the 7-probe FISH panel and stratification for myeloma and risk-adapted therapy (mSMART) classification for risk stratification. Results: We included 123 samples in the study. Results showed hyperdiploidy as the most common abnormality among newly diagnosed patients (110), with 54.5% (n = 60/110) classified as high-risk and 45.5% (n = 50/110) as standard-risk. Amplification of 1q was the most common abnormality in high-risk, while hyperdiploidy prevailed in standard-risk. Out of the 110 patients, 20.9% (n = 23) patients exhibited double-hit myeloma, and only two out of 110 (1.8%) had triple-hit myeloma. Among relapsed cases (13, 11.8%), all were high-risk, with amplification of 1p1q being the most common abnormality. Out of the 13 relapsed cases, five (38.4%) were double-hit myeloma, and one (7.7%) was triple-hit myeloma. In the remaining 7 (53.8%) cases, either one of the standard risk or high-risk abnormalities or both were observed. Conclusion: The 7-probe FISH panel was found to be a better and more comprehensive tool for risk stratification, molecular classification, and further management of multiple myeloma patients, and it led to improved patient care. Karyotyping, in contrast, did not yield any additional information and thus can be avoided.

Venous thromboembolism prophylaxis and multiple myeloma patients in real-life: Results of a large survey and clinical guidance recommendations from the IFM group

Venous thromboembolism (VTE) remains a critical issue in the management of patients with multiple myeloma (MM), particularly when immunomodulatory drugs (IMiDs) combined with dexamethasone therapy are being prescribed as first-line and relapse therapy. One possible explanation for the persistent high rates of VTE, is the use of inappropriate thromboprophylaxis strategies for patients starting antimyeloma treatment. To tackle the issue, the Intergroupe francophone du myélome (IFM) offered convenient guidance for VTE thromboprophylaxis in MM patients initiating systemic therapy. This guidance is mainly supported by the results of a large survey on the clinical habits regarding VTE of physicians who are substantially involved in daily care of MM patients. VTE prophylaxis should be considered for all patients treated with IMiDs in combination with dexamethasone, in the absence of significant comorbidities, such as renal failure or bleeding risk. Anticoagulant should be preferred to antiplatelet agents for thromboprophylaxis. Despite the absence of large randomized controlled trials comparing those attitudes/options, available data on direct oral anticoagulants, which are already used in daily management of MM patients, are consistent with their potential usefulness for VTE prophylaxis in such patients. However, in order to implement a personalized continuous improvement strategy, clinicians must to be organized to collect all the data regarding this management. In other situations, thromboprophylaxis should be evaluated by using risk models and after careful evaluation of the risk/benefit ratio.

Using Mass Spectrometry to Assess Disease Status in Treated Multiple Myeloma Patients

Introduction As multiple myeloma (MM) is a bone-marrow based disease, the majority of MRD studies have focused on sensitive bone-marrow based assays. However, to effectively monitor patients this would require sequential invasive procedures at semi-frequent intervals. Sensitive, non-invasive, blood-based assays which can detect the presence of MRD are needed to optimize the management of MM patients. Mass spectrometry (MS) is currently being investigated for its clinical utility at different points in the monoclonal gammopathy pathway, from screening to MRD detection. This study aimed to compare the sensitivity and prognostic utility of MS with other blood-based M-protein detection methods and bone marrow flow cytometry at active disease, best response and MRD timepoints. Methods MS analysis took place at The Binding Site laboratory (The Binding Site, UK) using a pre-commercial quantitative immunoprecipitation (QIP-MS) system. Mass spectra was acquired over an m/z range of 10,000 to 30,000 and analysis was performed by two independent readers. Both transplant eligible and non-transplant chemotherapy only patients were recruited at varying stages of disease and treatments. Median follow up was 18 months. A total of 190 serum samples from 87 individual patients were tested for the presence of M-protein by conventional methods (serum electrophoresis (SPEP), immunofixation (IFE), free light chain (FLC)) and MS. A bone marrow flow cytometry (NGF) assay was performed up to a sensitivity of 10 -6 at pre- and post-transplant for a subset of patients. Disease response was determined according to the IMWG criteria. Results and Discussion When compared to conventional techniques MS showed increased sensitivity over SPEP, IFE and FLC (Table 1). The 1 M-protein detected by SPEP and IFE but not by MS was a post-transplant sample which showed multiple oligoclonal peaks by MS where the original M-protein could not be determined due to not having a diagnostic MS result available. When evaluating the 37 samples from 19 individual patients which were MS positive and IFE negative it was found that 7/19 (37%) patients in this group relapsed during the course of the study. As SPEP, IFE and FLC analyses are often performed together, the utility of using MS alone was compared to an algorithm of SPEP/IFE/FLC tests, where if any of the conventional tests showed abnormality this was considered positive. Using this scenario, MS outperforms the conventional tests in the 190 samples evaluated - with 7 samples being MS positive only and 1 sample (discussed above) being negative by MS but positive by all SPEP/IFE/FLC. As expected, upon analysing the percentage of samples within each IMWG clinical response group which had a positive or negative MS results the percentage of samples with a negative MS result increased with greater depth of response whilst those in partial response or worse had no negative MS samples. However, even in the deepest response group, complete response, 77% of samples were MS positive, showing how MS outperforms the IMWG criteria. Progression free survival (PFS) analysis at the best response time point showed a significant survival advantage of having a MS negative result (p=0.007). When comparing MS against NGF results at bone marrow testing time points agreement at pre-transplant was 88%, with all samples being NGF positive but 22/25 being MS positive and 1 of these 3 discordant patients relapsing during the study. At post-transplant agreement was only 56%. However, evaluating PFS at the post-transplant time point showed that MS status had a significant effect on survival (p=0.02) (Figure 1) where IFE (p=0.44) did not and NGF only approached significance (p=0.051). Conclusion This study aimed to evaluate the viability of using MS to identify M-proteins in treated MM patients. In this study the MS method had a higher number of positive results than any of the conventional methods, and outcompeted the algorithm of SPEP/IFE/FLC in detecting the presence of M-protein. This study has shown a survival benefit of being MS negative at both post-ASCT and best response time points across a range of treatments. There were a high number of patients who were MS positive throughout monitoring and it will be important to determine how such a sensitive method can be used to provide clinically useful information to clinicians to give the best balance between treatment and quality of life for patients.

Anti-Angiogenic Activity of Drugs in Multiple Myeloma

Angiogenesis represents a pivotal hallmark of multiple myeloma (MM) that correlates to patients' prognosis, overall survival, and drug resistance. Hence, several anti-angiogenic drugs that directly target angiogenic cytokines (i.e., monoclonal antibodies, recombinant molecules) or their cognate receptors (i.e., tyrosine kinase inhibitors) have been developed. Additionally, many standard antimyeloma drugs currently used in clinical practice (i.e., immunomodulatory drugs, bisphosphonates, proteasome inhibitors, alkylating agents, glucocorticoids) show anti-angiogenic effects further supporting the importance of inhibiting angiogenesis from potentiating the antimyeloma activity. Here, we review the most important anti-angiogenic therapies used for the management of MM patients with a particular focus on their pharmacological profile and on their anti-angiogenic effect in vitro and in vivo. Despite the promising perspective, the direct targeting of angiogenic cytokines/receptors did not show a great efficacy in MM patients, suggesting the need to a deeper knowledge of the BM angiogenic niche for the design of novel multi-targeting anti-angiogenic therapies.

The evolving diagnosis and treatment paradigms of multiple myeloma in China: 15 years' experience of 1256 patients in a national medical center.

Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first-line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. Of the 1256 individuals, median age was 64 (range 31-89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light-chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high-risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short- and long-term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7months. Advanced ISS stage, HRCA, light-chain amyloidosis and EMD independently predicted an inferior PFS. First-line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light-chain amyloidosis, and receiving PI/IMiD-based regimen versus PI+IMiD-based regimen independently indicated a poorer OS. In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

Outcome in Multiple Myeloma Patients Treated in the Era of Modern Therapies Who Were Admitted to Intensive Care: A Retrospective Analysis from a Teaching Hospital between 2014 and 2019

There are major progress in the upfront and relapsed treatments of multiple myeloma (MM) patients with the immunomodulatory agents, proteasome inhibitors, anti-CD38 monoclonal antibody therapy. In this context of availability of multiple therapeutical options, admission policies and the management of MM patients with life-threatening events who require intensive care need to be reconsidered. In fact, there are few studies that evaluate these questions for MM patients treated with modern therapies. The objective of this retrospective study is to determine prognostic factors of MM patients admitted in intensive care unit (ICU) and evaluate their outcomes. Between June 2014 and December 2019, 72 MM patients were admitted in ICU of teaching hospital of Lyon, France ; on 620 patients with MM (12%). Medical history with clinical, biological and treatment data concerning MM were abstracted from medical records. We also collected medical variables related to intensive cares especially the causes of ICU admission, Sequential Organe Failure Assessment (SOFA) and Simplified Acute Physiology Score 2 (SAPS 2) and the management and events in ICU. Prognostic factors associated with 90-day mortality were investigated in univariate and multivariate analyses using Cox model. The median age of MM patients at the ICU admission was 67 years (62-74). The majority of patients were previously exposed to immunomodulatory agents (n=52, 72%), proteasome inhibitors (n=54, 75%), 19 (26%) received anti-CD38 monoclonal antibody and 27 (38%) received autologous stem cell transplantation (ASCT). The median of prior lines was 2 (1-3). At ICU admission, 29 (40%) patients were responders to therapy (complete remission/very good partial response/partial response) and 43 (60%) had progressive disease including patients at diagnosis (n=10, 14%). The median of days of ICU admission since the first day of hospitalization in conventional unit was 1 (0-2). The cause of ICU admission were as follows: shock (n=18, 25%), acute respiratory failure (n=18, 25%), disease progression (n=13, 18%), neurologic injury (n=6, 8%), cardiac injury (n=5, 7%), kidney injury (n=4, 6%), post surgery (n=4, 6%), hemorrage (n=3, 4%), public road accident (n=1 ; 1%). Twenty-three patients (32%) benefited from multiple ICU admission : 16 two stays, 4 three stays, 3 more than four stays. Mechanical ventilation was required for 24 patients (33%), with a median duration of 7 days (2-11), 4 patients (6%) had non-invasive ventilation, 4 (6%) had high-flow nasal oxygene and25 (35%) had nasal oxygene. Vasoactive drugs was required for 12 patients during a median of 3 days (2-6) and renal remplacement therapy was used in 9 patients. The median lengh of ICU stays was 5 days (2-8). In total, 15 patients (21%) died during ICU stays of differents causes : 8 (54%) of infection, 5 (33%) of disease progression, 2 (13%) of other cause. Fifty-two (72%) patients were put on anti-infectious therapies. The main clinical infections was pulmonary (50%). Documented infections was found in 29 patients (56%). The most common germs were Gram-negative bacteria (48%) and then virus (21%). Fifty-two (72%) patients were able to have subsequent MM therapies after ICU admission, with a median number of lines of 1 (0-2). The 90-days and one year OS rates since ICU admission (first stay) were 69% and 58%, respectively. In univariate analysis integrating variables at day 1 and before ICU admission, number of previous lines for MM treatment, time between MM diagnostic and ICU admission and lactate concentration were associated with 90-day mortality. In multivariate analysis, only lactate concentration (HR=1.13; 95%CI, 1.02-1.25; p=0.02) was associated with 90-day mortality (Table 1 and Figure 1). In a second multivariate analysis integrating also variables related to ICU management, only mechanical ventilation is associated with 90-day mortality (HR=3.68; 95%CI, 0.98-13.8; p=0.05). This retrospective study showed that the rate of mortality in ICU for MM patients treated with modern therapy is closed to general population (20%) in favor of a broad ICU admission policies for these patients. Lactate concentration was the unique independant variable of 90-day mortality which is in aggrement with findings observe in ICU general population. These data are in favour of a closed collaboration between hematologists and intensivists for an optimal management of MM patients with a life threatening events. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial.

Simple SummaryMultiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis.Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients.

Prognostic value of B-cell maturation antigen, CD56 expression and neutrophil lymphocyte ratio in patients with multiple myeloma

Introduction: B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and differentiation into plasma cells. CD56 is involved in the adhesion of myeloma cells to the bone marrow matrix. Thus, lack of CD56 expression is associated with a higher incidence of extramedullary disease. An elevated neutrophil-lymphocyte ratio (NLR) has been recognized as a poor prognostic factor in various hematological malignancies. The aim of this study was to evaluate the role of BCMA, CD56 and NLR as novel prognostic markers in multiple myeloma (MM). Material and methods: The study included 80 subjects, 40 MM patients, and 40 normal healthy age- and sex-matched controls. BCMA was analyzed by enzyme-linked immune sorbent assay. Flow cytometry was used for the determination of CD56 expression. NLR was calculated from the complete blood count differential count. All patients received six cycles of bortezomib, cyclophosphamide and dexamethasone (VCD). Treatment outcome was assessed and progression-free survival (PFS) was estimated using Kaplan-Meier survival analysis. Results: Patients who achieved complete remission showed lower BCMA levels, positive CD56 expression, and lower NLR. Moreover, higher BCMA levels and CD56 negative expression were significantly associated with shorter PFS. Conclusions: Our study emphasizes the importance of BCMA, CD56 and NLR to predict the clinical outcome in MM patients. This could help in better risk stratification and tailored clinical management of MM patients.

Measurable Residual Disease Assessment in Multiple Myeloma: How Deep Is Enough?

The introduction of new and more effective therapeutic options for Multiple Myeloma (MM) has significantly deepened and prolonged patients’ remission. As currently used treatment protocols induce high rates of complete responses, Measurable Residual Disease (MRD) assessment has become essential to enhance the evaluation of treatment efficacy. Detection of MRD has improved with the development of highly sensitive and standardized techniques such as Next Generation Flow or Next Generation Sequencing, complemented by functional imaging techniques. These advances offer a valuable opportunity to further optimize criteria of response to treatment. Currently, extensive data demonstrate that MRD status is a valuable prognostic factor of survival. Since MRD represents a real measurement of disease burden, its incorporation in clinical trials to guide treatment decisions will certainly translate into clinical benefits. Sustained MRD negativity can be used to consider optimal candidates for treatment discontinuation, whereas MRD positive high-risk patients may have access to novel immunotherapeutic strategies such as bispecific drugs or CAR T cell therapy. In this review, we describe the available techniques to detect MRD, address the current data regarding MRD as a surrogate endpoint within clinical trials, examine how MRD can be introduced into the clinical management of MM patients, and discuss the future of MRD monitoring.

Impact of COVID-19 on the Diagnosis and Management of Multiple Myeloma: Experience from a Canadian Center.

The impact of coronavirus disease-19 on the management of multiple myeloma (MM) has been recognized. However, the real effect on clinical outcomes remains poorly understood. We describe a local experience of the management of MM patients and report their outcomes during the current pandemic. All consecutive symptomatic MM patients seen at our center since 03/20 were evaluated. A cohort of 156 patients diagnosed from 01/19 to 12/20 was analyzed to interrogate differences in presentation patterns. A total of 553 MM patients were seen and/or treated at Tom Baker Cancer Center in the year of 2020. From those, 47.1% (n = 261) were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Sixteen patients tested positive and data are presented. In addition, a decrease of 21.7% in the rate of new smoldering MM/MM diagnosis was observed in 2020 as compared to 2019. Further, an increase in deaths was also observed in 2020. Our study confirms an increase lethality for MM patients infected with SARS-CoV-2. A balance between safety and need for cancer control should be emphasized.

Management of multiple myeloma patients with renal disease

Multiple myeloma (MM) is a plasma cell dyscrasia, accounting for 10% of all hematological malignancies, which translates into a global age-standardized incidence and mortality rate of 2:1 per 100.000 and 1.39 per 100.000 respectively (1). Kidney disease is a very common complication of MM, increasing the mortality and being a poor prognostic factor. Renal impairment is often the first reason for patient admission, leading to the plasma cell dyscrasia as being the cause. 40% of patients with cast nephropathy had previously undiagnosed myeloma (2).The aim of this paper is to show that Prompt diagnosis and initiation of therapy warrants better patient survival and delays, or even prevents organ damage in multiple myeloma.

Sustained Residual Disease Negativity Assessed By Diffusion-Weighted Whole-Body MRI (DW-MRI) Has Strong Predictive Relevance for Survival in Newly Diagnosed Multiple Myeloma Patients on Maintenance Therapy after Autologous Stem Cell Transplantation (ASCT)

Sustained Residual Disease Negativity Assessed By Diffusion-Weighted Whole-Body MRI (DW-MRI) Has Strong Predictive Relevance for Survival in Newly Diagnosed Multiple Myeloma Patients on Maintenance Therapy after Autologous Stem Cell Transplantation (ASCT)

NS-64: Lessons learned: patient management and outcomes of Multiple Myeloma patients during the COVID-19 pandemic in New York City

New York City (NYC) was an epicenter of COVID-19 pandemic in the United States during spring 2020. During March–May 2020, approximately 203,000 confirmed COVID-19 cases were reported among NYC residents including 54,211 (26.6%) known to have been hospitalized and 18,679 (9.2%) who died. NYC had a higher confirmed coronavirus case volume than any country in the world, besides the United States. Here, we discuss how advanced practitioners Providers (APPs) and Health Care Support Staff in the Multiple Myeloma (MM) program at Mount Sinai Hospital in NYC modified patient care guidelines during the COVID-19 pandemic in an effort to balance the need for social distancing and optimizing patient care. Cognizant of these key factors during the pandemic, oncology APPs, nurses, physicians, and staff at Mount Sinai convened to determine how patients should be best managed. Important considerations in addition to remission status and type of therapy (IV/SC or oral) included the patient’s performance status and chemotherapy oral adherence. Based on these, the group determined: (1) Newly diagnosed patients or relapsed patients with significant cytopenias who need parenteral therapy should continue with the current therapy, but the number of visits should be decreased to limit exposure to other HCPs. If the patient has had a good response to treatment, consider changing to an oral regimen. (2) Patients in remission (complete remission, very good partial remission) should consider switching therapy to an oral regimen (immunomodulatory agents, proteasome inhibitors, dexamethasone, and/or Histone deacetylase inhibitors). (3) Stem cell harvest and stem cell transplant should be delayed if the patient continues to respond to the current therapyOutcomesDuring this time we had 58 MM patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (>70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p<0.05) associated with hospitalization. Although several demographic factors and comorbidities increased the risk of hospitalization and mortality, myeloma therapy did not influence outcomes. In fact, survival was comparable to the overall population of New York during the pandemic. Our data supports the need to maintain proactive management of MM patients by balancing their need for therapy with the increased risk of hospitalization and death in a subset of MM patients with COVID-19.

P-221: Evolution of Dara-based regimen use along treatment lines from 2016 to 2019: a real-life study based on the French national claim database

P-221: Evolution of Dara-based regimen use along treatment lines from 2016 to 2019: a real-life study based on the French national claim database

Abstract 408: Quantification of cell surface HLA-A2 and intracellular Survivin protein levels for tumor blasts and non-blast immune cells in multiple myeloma bone marrow aspirates using a rapid sample preservation methodology followed by 10-color FACS assay

Abstract Introduction: Multiple myeloma (MM) is a plasma cell disorder characterized by clonal expansion and accumulation of immature undifferentiated neoplastic cells in the bone marrow (BM). Recent advances in fluorochrome chemistries, flow cytometry (FACS) instrumentation and rapid tissue preservation methodologies have created opportunities for broader adoption of FACS in the clinical management of multiple myeloma patients. Methods: We have developed a 10 color, 2 tube FACS assay based on recommendations made by the European Myeloma Network for phenotyping plasma cell gammopathies to identify abnormal blasts in multiple myeloma patient bone marrow aspirates. The assay includes essential plasma cell markers CD138, CD38, CD56 and CD19 to differentiate abnormal blasts from reactive plasma cells. Use of a multi epitope fluorochrome conjugated anti-CD38 antibody enables CD38 detection in patients on anti-CD38 therapy. Results: Quantification of cell surface HLA-A2 and intracellular survivin protein was made possible using fluorochrome conjugated antibodies in combination with bead standards. The SmartTube™ proteomic stabilizer system for rapid preservation was used to freeze BM aspirate specimens for later analysis at locations with appropriate FACS equipment and trained staff. Consistent with previously published literature, patient survivin levels were elevated on abnormal MM blasts in comparison to survivin levels on non-blast immune cells. Conclusion: We have developed a robust FACS methodology that would be easy to implement in the clinical trial and development setting with minimal training. The assay can consistently identify abnormal blasts in BM samples of multiple myeloma patients and quantify intracellular and cell surface biomarkers related to MM disease or disease treatment responses. Citation Format: Tejaswini Hardas, Hyun-Jeong Ra, James Sheridan, Maria Kovalenko, Catherine Tribouley. Quantification of cell surface HLA-A2 and intracellular Survivin protein levels for tumor blasts and non-blast immune cells in multiple myeloma bone marrow aspirates using a rapid sample preservation methodology followed by 10-color FACS assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 408.

Collaborative Physician-Pharmacist Multiple Myeloma Clinic Improves Guideline Adherence and Prevents Treatment Delays

Although survival of patients with multiple myeloma (MM) has improved in the last decade, achieving optimal outcomes requires timely delivery of anti-myeloma therapy as well as adherence to supportive care guidelines and patient education. We hypothesized that a multidisciplinary approach of a collaborative physician-pharmacist MM clinic would have a positive impact on clinical measures such as guideline adherence as well as improve the workflow process and prevent treatment delays.From March 2014 to February 2015, we initiated a collaborative MM clinic at our institution, whereby in addition to normal physician care, a dedicated board-certified oncology pharmacist provided consultation on all new and continuing patients. The pharmacist provided education and medication lists, completed medication reconciliation, monitored for adherence and side effects, recommended management of toxicity and supportive care, and navigated issues involving enrollment and access to oral specialty medications. All consultations were documented in the patient's medical chart using a template addressing these key components. Outcomes were compared to those of patients being treated by the same physician during the previous year, when ad-hoc pharmacist consultation was available (traditional model). We compared clinical measures related to guideline adherence and analyzed delays in obtaining immunomodulator drugs (IMiDs) using available dispensing records.Patient characteristics were similar between the collaborative and traditional models including age, sex, race, ISS stage, protein subtype, treatment type, and prior number of therapies. During the 12-month study period when a collaborative model was implemented, 399 pharmacist consultations occurred during 551 physician visits (n=57 patients). During the prior year when a traditional model existed, there were 26 pharmacist consultations on 355 physician encounters (n=44 patients) (7.3% versus 72.4%, p<0.0001).We observed improved adherence to bisphosphonates (BP) in the collaborative clinic (55 (96%) versus 30 (68%) patients, p=0.0002). Among patients receiving BP, the time to initiation from diagnosis and re-initiation after autologous stem cell transplant (ASCT) was 5.5 versus 97.5 days (p<0.001) and 12.5 versus 135 days (p<0.001) among the collaborative and traditional clinic, respectively. One hundred percent of patients in the collaborative clinic versus 41% of patients in the traditional clinic received concomitant calcium and vitamin D (p<0.001). In patients receiving IMID-based regimens, appropriate VTE prophylaxis was prescribed in 52 (100%) versus 29 (76%) patients in the collaborative and traditional clinic, respectively (p<0.0002). Appropriate use of acyclovir prophylaxis in patients receiving proteasome inhibitor-based treatment was observed more frequently in the collaborative clinic (98% versus 56%, p=0.004). Although the number of patients receiving Pneumocystis Jirovecii pneumonia prophylaxis post-ASCT was similar (93 versus 100 percent, p=0.4), the time to initiation of prophylaxis was shorter in the collaborative clinic (11 versus 40.5 days, p<0.0001). Finally, influenza vaccination administration was higher in the collaborative clinic (76 versus 24 percent, p<0.001). When analyzing delays in obtaining IMiD therapy, we found that the median time from when the treatment plan was noted in the medical chart to when the IMiD was first filled was 7 (range: 0-32) vs. 15 (range: 3-62) days in the collaborative and traditional clinic, respectively (p=0.002). Finally, there was a significant reduction in treatment delays observed in the collaborative compared to the traditional clinic (21% vs. 85% of patients undergoing a delay, p<0.0001).Here we pilot a multidisciplinary approach that leads to increased guideline adherence and prevents delay in anti-myeloma treatment. The collaborative clinic model could be applied to several different practice sites in order to establish an improved and more systematic approach in the management of MM patients. Prospective studies analyzing clinical outcomes, patient satisfaction and cost effectiveness of this approach are warranted. DisclosuresWirth:Celgene: Consultancy, Honoraria. Patel:Celgene: Consultancy, Honoraria.

Retrospective study to assess the impact of hepatitis C virus infection on the prognosis and management of multiple myeloma.

e20001 Background: Multiple Myeloma (MM) is a neoplasm of the post-germinal center, terminally differentiated B-cells. MM accounts for 1% of all types of cancer and 10% for all hematologic malignancies. Chronic hepatitis C virus (HCV) is an infection that affects over 71 million patients worldwide. Cytotoxic agents and immunosuppressive therapy as steroids are the main line of therapy in lymphoid malignancies, but these drugs may exacerbate chronic viral hepatitis and cause uncontrolled replication of hepatitis viruses. The impact of HCV infection on MM patients remains unclear. Objective: To assess the impact of HCV infection on the prognosis and management of MM patients. Methods: A 10-year retrospective study of MM patients was conducted at Cairo University Clinical Oncology Department from January 2009 to April 2019. Results: During this time, 150 patients were diagnosed with MM, 109 (72.7%) were HCV negative, 24 (16%) were HCV positive, and 17 (11.3%) with unknown HCV status. The median age was 51 and 54 years for HCV negative and positive groups respectively, with a statistically insignificant difference (p-value &gt; 0.2). In the multivariate analysis, HCV infection was not an independent factor related to overall survival (OS), however age, creatinine and hemoglobin levels correlated significantly with OS (p &lt; 0.009, 0.008, 0.031 respectively). The median OS for the HCV negative group was 31.11 months (95% CI: 22.62 - 39.61) compared to 37.66 months (95% CI: 7.19 - 68.13) for the HCV positive group. The median progression-free survival (PFS) for all patients was 18.9 months, for HCV positive patients was 15.36 months (95% CI: 13.18 – 17.54), and for HCV negative patients was 20.49 months (95% CI: 14.13 – 26.85). Age below 60 years and creatinine level less than 2 mg/dL were statistically significant for favorable disease-free survival (DFS) (p &lt; 0.030, 0.034 respectively). Conclusions: Age, creatinine and hemoglobin levels are significant prognostic factors in MM but HCV status doesn’t affect the overall survival or progression-free survival. HCV infection should not contraindicate MM therapy.

Optimizing transfusion management of multiple myeloma patients receiving daratumumab-based regimens.

Daratumumab, a human anti-CD38 monoclonal antibody used to treat multiple myeloma, interferes with pretransfusion testing and can mask alloantibodies. Incidence of alloimmunization in patients on daratumumab has not been well characterized, and optimal transfusion guidelines regarding prophylactic antigen matching, accounting for both patient safety and efficiency, have not been well established for these patients. Records of patients who received daratumumab between January 1, 2014 and July 2, 2019 were reviewed. Daratumumab interference with pretransfusion testing was managed by testing with reagent red blood cells (RBCs) treated with 0.2M dithiothreitol. When daratumumab was present during antibody testing, patients were transfused with RBC units prophylactically matched for D, C, c, E, e, and K antigens per hospital policy. Out of 90 patients identified, 52 received a total of 638 RBC transfusions (average of 12.3units per patient, SD 17.2, range 1-105, median 5 among those transfused). Alloantibodies existing before daratumumab initiation were identified in seven patients. No new alloantibodies were detected in any patients after starting daratumumab treatment. The incidence of alloimmunization in patients receiving daratumumab is low. Whether this is due to the effect of daratumumab, underlying pathophysiology, or other factors, is unknown. Because these patients require a large number of RBC transfusions overall and have little observed alloimmunization, phenotype matching (beyond RhD) may be unnecessary. Since the use of dithiothreitol cannot rule out the presence of anti-K, we recommend transfusion of ABO-compatible units, prophylactically matched for the D and K antigens only.

Minimal Residual Disease in Multiple Myeloma: Ready for Prime Time?

Minimal residual disease (MRD) techniques are essential to identify the small clonal fraction within and outside the bone marrow. In the last years, evidence regarding their prognostic role for the evaluation of the depth of response of current treatment strategies has grown rapidly. Consequently, MRD was incorporated in an increasing number of clinical trials for multiple myeloma patients, also as primary endpoint, and even to guide therapeutic choices. A robust correlation between MRD negativity and survival was established. Yet, several issues regarding MRD evaluation remain to be addressed: from the optimal and more cost-effective techniques for its assessment and its harmonization worldwide to its use in clinical practice to its impact on treatment modulation. This review focuses on the available evidence supporting the use of MRD status for the management of multiple myeloma patients and on open issues that still need an answer.