Bone Marrow Plasma Cell Percentage Research Articles

The quantitative parameters based on marrow metabolism derived from synthetic MRI: A pilot study of prognostic value in participants with newly diagnosed multiple myeloma.

The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (<VGPR) groups after four treatment cycles. Univariate, multivariate analyses and ROC were used to identify prognostic significance. Mann-Whitney U-tests were used to compare the SyMRI parameters between genders. The value of optimizing the risk stratification was analyzed by Fisher's exact tests at each R-ISS stage. Fifty-nine participants (good response, n = 33; poor response, n = 26) were evaluated. The bone marrow plasma cell percentage, β2-microglobulin, T1 and T2 value were difference between two groups (all p < 0.05). The T1 (odds ratio 1.003, p = 0.005) and T2 values (odds ratio 0.910, p = 0.002) were independent predictors and the AUC and cut-off values were 0.787, 967.2 ms and 0.784, 75.9 ms, respectively. There were no significant differences in SyMRI parameters between genders. Participants with both T1 value ≥967.2 ms and T2 value ≤75.9 ms in the R-ISS II stage were potentially to get poor response. Synthetic MRI is a promising tool for predicting early treatment response to MM and promoting R-ISS II stage risk stratification.

Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in Patients with Relapsed-Refractory Multiple Myeloma (RRMM) Not Meeting the Karmma Trial Eligibility Criteria: A Real-World Multicenter Study

Background: Ide-cel is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CART) therapy approved for RRMM after ≥4 prior lines of therapy (LOT), based on the results of the pivotal KarMMa trial. While response rates and survival outcomes have been very promising, patients (pts) with significant comorbidities, poor performance status (PS), aggressive disease characteristics, and prior BCMA-directed therapy (BDT) exposure were excluded from the KarMMa trial. There is an unmet need, therefore, to characterize outcomes in this real-world population. In this multicenter study, we evaluated real-world outcomes of pts not meeting the KarMMa trial eligibility criteria, treated with standard of care (SOC) ide-cel. Methods: Three US academic centers, part of the US Myeloma Innovations Research Collaborative, contributed data to this retrospective analysis, which included pts who had undergone apheresis up until 5/15/2023 and who were infused with SOC ide-cel. We compared our cohort (SOC cohort) with the KarMMa cohort for safety outcomes, including cytokine-release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematologic toxicities, as well as efficacy outcomes, including overall response rate (ORR), complete response or better (≥CR), progression-free (PFS) and overall survival (OS). Binomial exact test and Kaplan Meier method were used for statistical analysis. Results: 120 pts were leukapheresed, 77 (64%) did not meet the KarMMa eligibility criteria, and 69 (58%) of them proceeded with ide-cel infusion and had at least 30-day follow-up available for safety and efficacy assessments. Among the 69/120 SOC ide-cel recipients included in the analysis, median age was 64 (range 41-79) years and 49% were male. The main reasons for not meeting KarMMa inclusion criteria were: baseline 3-4 cytopenia (39%), prior BDT (26%), renal impairment (CrCl &amp;lt;45 ml/min) (19%), ECOG PS ≥2 (14%) and history of other malignancy (13%); the rest are summarized in Table 1.Pts were heavily pretreated with a median of 6 (4-18) prior LOT and 36% had high-risk cytogenetics (del-17p, t[4;14], t[14;16], t[14;20]) prior to ide-cel infusion. The SOC cohort had more extramedullary disease (52% vs 39%, p=0.02), whereas the KarMMa cohort had higher median bone marrow plasma cell percentage (51% vs 29%, p=0.0002); other baseline characteristics including age, gender, prior LOT, high-risk cytogenetics, and prior refractoriness were similar among the two cohorts. CRS occurred in 81% (grade ≥3, 4%) of SOC pts vs 84% (grade ≥3, 5%) of KarMMa pts (p=0.51). ICANS occurred in 28% (grade ≥3, 3%) of SOC pts vs 18% (grade ≥3, 3%) of KarMMa pts (p=0.04). Infection rate &amp;lt; 8 weeks post-infusion for SOC vs KarMMa cohorts was 38% vs 49% (p=0.39) (bacterial 22% vs 13%, viral 13% vs 12%, fungal 0% vs 5%). Grade 3-4 cytopenias post-infusion for SOC vs KarMMa cohorts were as follows: anemia 48% vs 60% (p=0.10), neutropenia 87% vs 89% (p=0.43), and thrombocytopenia 65% vs 52% (p=0.02). With a median follow-up of 10 and 13.3 months (mo) for SOC and KarMMa cohorts, respectively, ORR was paradoxically higher for the SOC cohort (93% vs 73%, p=0.0008); likewise, ≥CR rate was also higher for the SOC cohort (48% vs 33%, p=0.04). The median PFS of SOC pts (7.6 mo, 95% CI, 6.2-10.9) (Figure 1) was comparable to KarMMa pts (8.8 mo, 95% CI, 5.6-11.6) (c-index 0.96). Likewise, median PFS of SOC pts who achieved ≥CR (10.9 mo, 95% CI, 9-18.3) was comparable to KarMMa pts (20.2 mo, 95% CI, 12.3-NR) (c-index 0.75). The median OS of SOC vs KarMMa cohorts were similar 19.4 mo (95% CI, 12.5-NR) vs 19.4 mo (95% CI, 18.2-NR) (c-index 0.7). Conclusion: Most safety aspects including CRS, infections and hematological toxicities (except thrombocytopenia) were similar between our real-world cohort and the pts who received ide-cel in the KarMMa study. ICANS was higher in the SOC cohort, however, rate remained low, and most events were grade 1-2. The survival outcomes were comparable between the two cohorts, with responses being, interestingly, higher in the SOC cohort. Our results demonstrate that ide-cel has comparable efficacy and safety in the real-world population, including those with prior BCMA therapy exposure, grade 3-4 cytopenias, ECOG ≥2 and significant comorbidities. These findings support broadening the inclusion criteria of future trials evaluating ide-cel in an effort to improve accessibility across RRMM pts.

Outcomes of BCMA-Directed Chimeric Antigen Receptor T-Cell (CART) Therapy in Patients with Relapse-Refractory Multiple Myeloma with Extramedullary Disease

Background: Presence of extramedullary disease (EMD) is associated with poor outcomes for patients with relapsed-refractory multiple myeloma (RRMM) and has been identified as a major risk factor for early progression (≤ 3 months) after CAR T-cell therapy. Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are B-cell maturation antigen (BCMA) targeting CAR T-cell therapies approved for patients with RRMM who have received ≥4 prior lines of therapy (LOT). This is a multicenter retrospective study on the real-world safety and efficacy of commercially available ide-cel and cilta-cel in heavily pretreated RRMM patients with EMD. Methods: Three U.S. academic centers, part of the U.S. Myeloma Innovations Research Collaborative (USMIRC), contributed data to this analysis, which included patients with RRMM who had received an ide-cel or cilta-cel infusion ≥30 days prior to data-cut off (7/1/2023). Baseline patient characteristics were outlined by descriptive analyses. Responses including overall response (ORR), and complete response or better (≥CR) rates were evaluated using the International Myeloma Working Group (IMWG) criteria. Statistical analysis was done with the Fisher's exact test and Kaplan Meier method for progression free (PFS) and overall survival (OS) calculations. Results: A total of 132 patients who received commercial (standard of care) BCMA-directed CAR T-cell therapy between 5/1/2021 and 5/30/2023 were included in this study. Out of these, 64 (48%) patients had a previous history or existing EMD prior to CART infusion. Table 1 summarizes the main patient characteristics and outcomes stratified as EMD and non-EMD groups. Both groups had comparable baseline patient and disease characteristics including median age, ECOG performance status, median bone marrow plasma cell percentage, high-risk cytogenetics, number of prior LOT, refractoriness status prior to CART and type of CAR T-cell product received. CART-related toxicities were comparable between the EMD and the non EMD groups. Cytokine release syndrome (CRS) was seen in 73% (≥ grade 3: 5%) of EMD patients vs 79% (≥ grade 3: 4%) of non-EMD patients (p=0.79). Likewise, immune effector cell-associated neurotoxicity syndrome (ICANS) was noted in 28% (≥ grade 3: 5%) of EMD patients vs 32% (≥ grade 3: 9%) of non-EMD patients (p=0.72). Infections were seen in 39% of the EMD group vs 28% of the non-EMD group (p=0.38). Response rates were also similar between the EMD vs non EMD cohorts: ORR 78% vs 96% (p=0.44); and ≥CR rate 42% vs 51% (p=0.54), respectively. With a median follow up of 7.2 (range 0.5-22.8) months for the entire patient cohort, the estimated median PFS was inferior for the EMD group (6.5 months [95% CI, 5.1-9.6]) compared to the non-EMD group (9.8 months [95% CI, 8.2-16.4]) (p=0.017) (Figure 1). At the time of data cut-off, 43 patients had died, 77% from disease progression, 11.5% from CART-related complications and 11.5% from unrelated causes. The estimated median OS was significantly worse for the EMD group (12.9 months [95% CI, 9.5-NA]) compared to the non-EMD group (19.4 months [95% CI, 1.2-NA]) (p=0.031). Conclusions: This is the largest multicenter retrospective study delineating the real-world outcomes of ide-cel and cilta-cel CAR T-cell therapies in RRMM patients with the high-risk disease feature of EMD. Based on our results, patients with prior history or presence of existing EMD at the time of CART infusion did not have any excessive treatment-related toxicities. However, these patients did experience shorter PFS and OS compared to patients without EMD highlighting the presence of EMD as a risk factor for poor outcomes after CART. Therefore, this group of patients should be considered for pre- and post-CART risk mitigation strategies aiming to prevent disease progression and improve survival outcomes.

Clinician preferences on treatment of smoldering myeloma: a cross-sectional survey

Smoldering myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM) with a variable risk of progression. The management of high-risk SMM (HR-SMM) remains controversial, particularly with changes in diagnostic criteria that led to reclassifying of some patients with SMM to MM. This study aimed to assess clinician preferences for whether to treat patients with HR-SMM and/or patients with MM diagnosed solely by SLiM criteria (free light chain ratio >100, bone marrow plasma cell percentage >60, greater than two focal marrow lesions on MRI) through an electronic survey. This was a cross-sectional survey of clinicians, conducted via an anonymous online REDCap survey from May 16th to July 5th, 2023. The survey included questions on demographics, SMM surveillance practices, and management preferences for two clinical scenarios (HR-SMM and MM based solely on the free light chain ratio >100 criterion). Data was analysed descriptively via Microsoft Excel. A total of 146 clinicians completed the full survey, with 92% recommending against routine treatment for a patient with HR-SMM based on a single time point assessment, instead preferring active surveillance. For patients with MM diagnosed solely on the basis of a free light chain ratio >100, 61% recommended active treatment, while 37% recommended active surveillance. The most common reasons recommending against treatment of HR-SMM were toxicity, lack of demonstrated overall survival benefit, and low MM-defining event rates in clinical trials. The survey indicates that most clinicians recommend against routine treatment for HR-SMM. Active surveillance is the prevailing standard of care and it is therefore an appropriate control arm in future SMM trials. More randomised trials are needed to determine if early treatment of modern-era SMM offers a net benefit to patients. None.

Comprehensive analysis and establishment of a prognostic model based on non-genetic predictors in multiple myeloma.

Multiple myeloma (MM) is a systemic hematological malignancy usually incurable. The value of some important prognostic factors may gradually decrease. We aimed to explore the non-genetic indexes, prognostic models, and significance of clinical staging systems of MM. A retrospective analysis was conducted on clinical data from 110 patients with MM who first visit the First Affiliated Hospital of Guangzhou Medical University between September 2005 to December 2018. Bone marrow plasma cell percentage (BMPC%), cystatin C (CysC), and β2 microglobulin (β2-MG) were positively correlated with Durie-Salmon (D-S) and international staging system (ISS) stages, while red blood cell count (RBC) and hemoglobin volume (HGB) were negatively correlated (P< 0.05). Univariate analysis showed that ISS stage, treatment protocol, immunofixation electrophoresis (IFE), ratio of red cell distribution width to platelet count (RPR), monocyte count (MONO), lactate dehydrogenase, and immunoglobulin G were significantly associated with the three-year overall survival (OS). IFE, treatment protocol, and β2-MG significantly affected progression-free survival (P< 0.05). Multivariate analysis showed that the treatment protocol, ISS stage, RPR, MONO, and IFE were independent prognostic factors for three-year OS (P< 0.05). BMPC%, CysC, and β2-MG were positively correlated with both clinical staging systems and RBC and HGB were negatively correlated. RPR and MONO affect MM prognosis and the established prognostic model can guide patient prognosis.

LINKER-MM1 study: Linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

8006 Background: Linvoseltamab is a BCMA×CD3 bispecific antibody with encouraging efficacy and a manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (RRMM) (Bumma et al. ASH 2022). Two Phase (Ph) 2 full dose cohorts (50 mg and 200 mg) in the LINKER-MM1 (NCT03761108) trial were studied to optimize dose selection. Methods: Ph 2 enrolled adults with MM who progressed on/after ≥3 lines of therapy (LoT) including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody (Ab), or were at least triple class (IMiD/PI/anti-CD38 Ab) refractory. A protocol amendment permitted pts who progressed during 4–12 wks on 50 mg to dose escalate to 200 mg. Primary endpoint was objective response rate (ORR). Key secondary endpoints included duration of response (DoR) and minimal residual disease status. Results: As of 1 Sept 2022, 252 pts have enrolled (Ph 1: 73; Ph 2: 179 [200 mg: 75; 50 mg: 104]). Median age was 66 yrs (range 37–90), 12% had extramedullary plasmacytomas, 12% high-risk cytogenetics, 37% bone marrow plasma cell percentage (BMPC) ≥50%. Median soluble BCMA concentration (sBCMA) was 0.43 mg/L (range 0–10.2), median prior LoT: 5 (range 1–16), and 81% were ≥triple class refractory. Numerically higher efficacy was observed with 200mg, including in high disease burden subgroups; ORR was 64% (200 mg cohort; n = 58, includes 12 Ph 1 pts) and 50% (50 mg cohort; n = 104). Subgroup analyses showed higher ORR in the 200 mg cohort versus 50 mg for sBCMA ≥0.4 mg/L (52% vs 37%), BMPC &gt; 67% (64% vs 35%) and revised ISS stage III (71% vs 27%). Median DoR was not reached for both cohorts (median follow-up: 2.3 months [200 mg], 4.7 months [50 mg]). Probability of maintaining response at 6 months was 89% (200 mg) and 85% (50 mg). Eight pts dose escalated from 50 to 200 mg; 6 (75%) achieved a response. Treatment-emergent adverse events (TEAEs) occurred in 95% (Grade [Gr] ≥3: 66%) of pts in the 200 mg cohort (n = 87, includes 12 Ph 1 pts) and 100% (Gr ≥3: 80%) in the 50 mg cohort. The most common TEAEs were cytokine release syndrome (200 mg: 37% [Gr 3: 1%]; 50 mg: 53% [Gr 3: 2%]), fatigue (200 mg: 32% [Gr ≥3: 0]; 50 mg: 33% [Gr ≥3: 0]) and anemia (200 mg: 28% [Gr ≥3: 24%]; 50 mg: 40% [Gr ≥3: 36%]). Grade ≥3 ICANS occurred in 2 pts (2%) in the 200 mg cohort and 1 pt (1%) in the 50 mg cohort. TEAEs leading to treatment discontinuation occurred in 7% (200 mg cohort) and 8% (50 mg cohort) of pts. Infections occurred in 43% (Gr ≥3: 26%) in the 200 mg cohort and 59% (Gr ≥3: 31%) in the 50 mg cohort. Conclusions: Linvoseltamab 200 mg showed better efficacy compared with 50 mg, including in pts with high disease burden. The 200 mg dose had consistent efficacy across high-risk subgroups and induced responses in pts who progressed on 50 mg. Safety was consistent across Ph 2 doses. The recommended linvoseltamab dose for further development is 200 mg. Updated data with longer follow-up and complete enrollment of the 200 mg cohort will be presented at the meeting. Clinical trial information: NCT03761108 .

Associations between M-protein and bone marrow fibrosis in newly diagnosed multiple myeloma

Objectives: Myelofibrosis may occur as a primary condition or secondary to several malignant or non-malignant conditions. Multiple myeloma (MM) is a malignant condition in which collagen fibrosis and reticulin fibrosis may coexist. This study aimed to investigate the prevalence of bone marrow fibrosis in newly diagnosed MM and potential associations between serum M-protein concentrations and bone marrow fibrosis. Material and Methods: Ninety patients with newly diagnosed MM were retrospectively assessed in this study. Demographic characteristics, blood counts, blood biochemistry, bone marrow plasma cell percentage, and bone marrow fibrosis grades were recorded. Results: The bone marrow plasma cell percentage was ≥50% in 34.4% of patients and &lt;50% in 65.6% of patients. The bone marrow plasma cell percentage was found to be 55% in the high fibrosis group and 42% in the low fibrosis group (P = 0.04). Bone marrow fibrosis was detected at a high level in 23.3% of the patients. No statically significant differences were found between the high fibrosis group and the low fibrosis group in the parameters, including age, sex, the type of myeloma, hemoglobin concentrations and platelet counts at diagnosis, β2 microglobulin, lactate dehydrogenase, disease stage, and erythrocyte sedimentation rate that were assessed in the study (P &gt; 0.05). A statically significant association was found between lower fibrosis levels and higher Ig M and serum kappa levels and serum kappa/lambda ratio (P = 0.02, P = 0.03, and P = 0.03, respectively). Conclusion: In this study, significant correlations were found between low-grade bone marrow fibrosis to high IgM and the kappa/lambda ratio. In conclusion, in this study, it was shown that bone marrow fibrosis in MM differs according to subtypes.

Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study

Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma. In this retrospective, multicohort study, we included patients who were 18 years or older with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma. We evaluated several modelling approaches for predicting disease progression to multiple myeloma using a training cohort (with patients at Dana-Farber Cancer Institute, Boston, MA, USA; annotated from Nov, 13, 2019, to April, 13, 2022). We created the PANGEA models, which used data on biomarkers (monoclonal protein concentration, free light chain ratio, age, creatinine concentration, and bone marrow plasma cell percentage) and haemoglobin trajectories from medical records to predict progression from precursor disease to multiple myeloma. The models were validated in two independent validation cohorts from National and Kapodistrian University of Athens (Athens, Greece; from Jan 26, 2020, to Feb 7, 2022; validation cohort 1), University College London (London, UK; from June 9, 2020, to April 10, 2022; validation cohort 1), and Registry of Monoclonal Gammopathies (Czech Republic, Czech Republic; Jan 5, 2004, to March 10, 2022; validation cohort 2). We compared the PANGEA models (with bone marrow [BM] data and without bone marrow [no BM] data) to current criteria (International Myeloma Working Group [IMWG] monoclonal gammopathy of undetermined significance and 20/2/20 smouldering multiple myeloma risk criteria). We included 6441 patients, 4931 (77%) with monoclonal gammopathy of undetermined significance and 1510 (23%) with smouldering multiple myeloma. 3430 (53%) of 6441 participants were female. The PANGEA model (BM) improved prediction of progression from smouldering multiple myeloma to multiple myeloma compared with the 20/2/20 model, with a C-statistic increase from 0·533 (0·480-0·709) to 0·756 (0·629-0·785) at patient visit 1 to the clinic, 0·613 (0·504-0·704) to 0·720 (0·592-0·775) at visit 2, and 0·637 (0·386-0·841) to 0·756 (0·547-0·830) at visit three in validation cohort 1. The PANGEA model (no BM) improved prediction of smouldering multiple myeloma progression to multiple myeloma compared with the 20/2/20 model with a C-statistic increase from 0·534 (0·501-0·672) to 0·692 (0·614-0·736) at visit 1, 0·573 (0·518-0·647) to 0·693 (0·605-0·734) at visit 2, and 0·560 (0·497-0·645) to 0·692 (0·570-0·708) at visit 3 in validation cohort 1. The PANGEA models improved prediction of monoclonal gammopathy of undetermined significance progression to multiple myeloma compared with the IMWG rolling model at visit 1 in validation cohort 2, with C-statistics increases from 0·640 (0·518-0·718) to 0·729 (0·643-0·941) for the PANGEA model (BM) and 0·670 (0·523-0·729) to 0·879 (0·586-0·938) for the PANGEA model (no BM). Use of the PANGEA models in clinical practice will allow patients with precursor disease to receive more accurate measures of their risk of progression to multiple myeloma, thus prompting for more appropriate treatment strategies. SU2C Dream Team and Cancer Research UK.

Effects of teclistamab and talquetamab on soluble BCMA levels inpatients with relapsed/refractory multiple myeloma.

B-cell maturation antigen (BCMA) is selectively expressed as a surface protein on plasma cells and is a validated target for multiple myeloma (MM). A soluble form of BCMA (sBCMA) is elevated in the sera of patients with MM. The bispecific antibodies teclistamab (BCMA×CD3) and talquetamab (G protein-coupled receptor family C group 5 member D [GPRC5D]×CD3) are in clinical development as therapies for MM. Using data from patients with relapsed/refractory MM (N=300) who participated in phase 1 studies of teclistamab (NCT03145181) or talquetamab (NCT03399799), baseline serum sBCMA levels were quantitatively analyzed relative to response to treatment, percentage of bone marrow plasma cells (BMPCs), and cytogenetic risk. By cycle 3 day 1 of treatment, sBCMA levels declined from baseline in 50 (88%) of 57 responders and 49 (98%) of 50 responders to teclistamab and talquetamab, respectively. Depth of response correlated with the magnitude of sBCMA reduction. In contrast, sBCMA increased in 33 (80%) of 41 patients and 24 (49%) of 49 patients who did not respond to teclistamab or talquetamab, respectively. Baseline sBCMA levels correlated with the percentage of BMPC; patients with extramedullary plasmacytomas who had low levels of BMPC (≤10%) tended to have high baseline sBCMA levels (≥400 ng/mL), based on limited data. Baseline sBCMA levels and changes in sBCMA levels at cycle 3 day 1 were similar in patients with high- and standard-risk cytogenetics treated with teclistamab or talquetamab. These results support the use of sBCMA as a potential surrogate marker of tumor burden and treatment response in MM.

A Retrospective Study of Antibody Titers in Patients with Plasma Cell Disorders

Background: Recent studies have estimated that infections occur with increased risk in patients with plasma cell disorders as compared to the general population. Our group has previously shown that patients who show response to vaccination following autologous hematopoietic stem cell transplantation (AHCT) have better overall survival and progression free survival than those who do not. In clinical practice, antibody titers against pathogens that are targeted by vaccines are measured infrequently in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM) at the time of diagnosis. Moreover, studies have previously shown that AHCT and maintenance therapy can cause seroconversion of titers in MM patients but the effect of induction chemotherapy on seroconversion of antibody titers is unknown. Methods: The study population comprised of controls and patients with plasma cell disorders who were seen at Roswell Park Comprehensive Cancer Center from 2018-2022. Controls were defined as patients consulted to our service to rule out gammopathies but found to be negative on initial testing. Immunoparesis was defined as deficiency of uninvolved immunoglobulins. All individuals had antibody titers tested at the time of first diagnosis. Patients with MM who underwent induction chemotherapy followed by AHCT had antibody titers tested prior to AHCT. Serological titers were measured according to Roswell Park Central Clinical Laboratory standards. Interpretation of individual titer results was in accordance with the manufacturers’ recommendations and published literature. Differences of the titers were compared by non-parametric Kruskal-Wallis Test /General Linear Regression Model (for continuous variables) and Fisher's Exact Test. SAS version 9.4 (SAS Institute, Cary, NC) was used for statistical analyses. All tests were two-sided and performed at a nominal significance level of 0.05. Results: A total of 101 patients including 24 (23.8%) controls, 21 (20.8%) MGUS patients, 16 (15.8%) SMM and 40 (39.6%) MM patients were included in the study. At the time of first diagnosis, controls had the greatest number of positive titers (mean 14.21, SD 3.48) followed by patients with MGUS (mean 13.86, SD 3.18), SMM (mean 11.06, SD 3.89) and MM (mean 9.33, SD 4) (p<0.0001), respectively (Figure 1). A total of 66 (65%) patients had a bone marrow biopsy performed at the time of diagnosis, including 12 (11.9%) patients with MGUS, 16 (15.8%) patients with SMM and 38 (37.6%) patients with MM. On linear regression analysis, there was a negative correlation between the number of positive titers and bone marrow plasma cell percentage (p=0.0009). Next we stratified patients with plasma cell disorders into those with immunoparesis (n=54) and those without immunoparesis (n=23) at the time of measurement of antibody titers. The number of positive titers were significantly higher in patients without (Mean 13.57, SD 3.53) than those with immunoparesis (Mean 9.80, SD 3.97) (p=0.0002). In total 48 patients including 12 (11.9%) MGUS patients, 10 (9.9%) SMM patients and 26 (25.7%) MM patients had peripheral blood flow cytometry for CD19+ B cell percentage at the time of measurement of antibody titers. On linear regression analysis, there was a positive correlation between the number of positive titers and the CD19+ B cell percentage (p=0.018). We further studied the seroconversion of antibody titers with induction chemotherapy and 22 out of 40 patients had both pre-and post induction treatment titers. Among them, 8 (36.4%) had seroconversion of titers from negative to positive for at least 3 pathogens without revaccination. Conclusion: Antibody titers for vaccine preventable diseases are lower in patients with MGUS, SMM and MM as compared to controls at the time of diagnosis. Current guidelines for revaccination are not extended to patients with MGUS and SMM and have to be investigated in prospective clinical trials before they can be generally recommended. Factors such as bone marrow plasma cell percentage, immunoparesis and CD19+ B cell percentage correlate with the number of positive titers. In MM patients undergoing AHCT, more than a third showed seroconversion of antibody titers from negative to positive prior to AHCT without revaccination, suggesting a role of induction chemotherapy in augmenting the immune response by reducing tumor burden. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High Metabolic Tumor Volume Is Associated with Higher Toxicity and Decreased Efficacy of BCMA CAR-T Cell Therapy in Multiple Myeloma

Background Recently, two chimeric antigen receptor T-cell (CAR-T) constructs have been FDA approved for relapsed/refractory multiple myeloma (RRMM) after exposure to at least 4 prior lines of therapy. High tumor burden has been associated with inferior outcomes, reduced CAR-T expansion and higher rates of toxicity. Patients relapsing after multiple lines of therapy more frequently have oligosecretory and extra-medullary disease that may not be well captured by serum-based markers of disease or bone marrow infiltration, respectively. Functional imaging with FDG-PET is well established as a useful tool in patients with myeloma but its prognostic impact in highly refractory patients or those proceeding with CAR-T has not been described. Metabolic tumor volume (MTV) capturing all metabolically active disease can be useful as a more global assessment of disease burden. We sought to evaluate tumor burden as measured by MTV in a cohort of patients presenting for anti-BCMA CAR-T with RRMM. Methods We identified all patients presenting to our center treated with anti-BCMA CAR-T with available restaging imaging performed within 60 days prior to lymphodepleting chemotherapy (LD-chemo). Baseline skull to midthigh with or without leg/whole-body 18F-FDG PET/CT scans were evaluated for MTV using a custom tool implemented on MIM PACS version 7.1 (MIM Software, Cleveland, OH) as previously reported (Dean et al, Blood Adv 2020). Briefly, images were semi-automatically analyzed to identify abnormal regions with reference to average metabolic activity of normal liver defined by PET SUV. Metabolically active volume at the lesion level were converged based on PERCIST criteria (41% of SUVmax). Summation of the metabolically active volumes across the human body is reported as the Metabolically Tumor Volume (MTV), measured in ml. Patient image scans were reviewed centrally by a radiologist blinded to outcomes, who removed any false positive uptake unrelated to metabolically active disease. Patients with the following FISH cytogenetics were considered high risk (HR): t(4;14), t(14;16) and deletion 17p/monosomy 17 whereas the remainder were standard risk (SR). The high and low tumor volume groups were selected based on the median MTV value in cohort. Baseline laboratory tests (e.g. beta2 microglobulin (b2M), C-reactive protein (CRP)) and repeat bone marrow biopsy were obtained prior to LD-chemo. Soluble BCMA (sBCMA) was measured by ELISA on patients with available serum samples (R&D Systems, MN, USA #DY193). All analyses were conducted in Stata (16.1, StataCorp LLC, College Station, TX). Results The study cohort consisted of 66 patients. Median age was 65 years (range 36 - 81), 55% were male, 55% had ECOG 0-1 prior to LD-chemo and 65% received bridging therapy. 25 (38%) were categorized as HR based on FISH cytogenetics. Patients had received a median of 6 prior lines of therapy and median interval between PET and date of CART infusion was 14.5 days (range 2-54). Median MTV was 26.3ml (0.26-1073.87ml) and only 3/66 (5%) had no measurable PET-avid lesions captured by this algorithm. Patients with high MTV (>26) were more likely to have elevated baseline CRP >0.5mg/dL (p=0.007) and receive bridging therapy (60% vs 40%, p=0.02). MTV correlated with sBCMA levels on day -6 (r=0.82, p=0.003), and with baseline b2M (r=0.47, p=0.005), but MTV did not correlate well with percentage plasma cells in pre-CAR-T bone marrow biopsy (r=0.12, p=0.3). The risk of ³G2 CRS was significantly higher (44% vs 12%, p=0.02) and any grade ICANS was numerically higher (27% vs 12%, p=0.1) in those with high vs low MTV, respectively. Finally, fewer patients with high MTV achieved CR by D30 (19% vs 31%, p=0.2) and with limited follow up 12/14 (86%) of deaths had occurred in patients with high baseline MTV (p=0.003). Conclusion These preliminary data confirm the added value of MTV calculated from baseline imaging as part of standard of care in patients with heavily pre-treated relapsed myeloma presenting for anti-BCMA CAR-T therapy. MTV correlated highly with sBCMA measured at day-6 and may be more representative for risk assessment than basing burden on bone marrow plasma cell percentage, which has not demonstrated a consistent relationship in predicting adverse events to date. High MTV appears to be associated with an increased risk of CAR-T specific adverse events and inferior outcomes and warrants further investigation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes in Patients with Renal Monoclonal Immunoglobulin Deposition Disease

BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the production of abnormal monoclonal immunoglobulins that deposit in the kidney and other organs. MIDD causes proteinuria, renal damage and eventually renal failure. Currently, there are few studies on the outcomes of patients (pts) with renal MIDD (R-MIDD). METHODS: We performed a single-center retrospective analysis on patients that were seen at the University of California San Francisco Hematology clinic for MIDD from 2010 to 2020. All pts must have had biopsy-proven R-MIDD. Demographic and disease-related characteristics at diagnosis were collected as well therapies administered. Diagnosis of multiple myeloma was per IMWG criteria (Rajkumar et al. Lancet Oncology 2014). Hematologic response and renal response were assessed per previously published criteria (Palladini et al. J Clin Oncol 2012; Palladini et al. Blood 2014). Overall survival (OS), time-to-next treatment (TTNT), time-to-renal progression (TTRP), time-to-dialysis (TTD) were estimated using the Kaplan-Meier method. TTRP was defined as time from the start of treatment to renal progression censored by last follow-up or date of renal transplant. TTD was defined as time from start of treatment to dialysis or last follow-up. Pts already on dialysis at diagnosis were excluded from TTRP and TTD. RESULTS: Thirty-four pts with R-MIDD were identified, 31 light chain deposition disease, 2 heavy chain deposition disease and 1 light and heavy chain deposition disease. Median age at diagnosis was 63 (IQR 58-70) with 13 (38.2%) females. Median creatinine and estimated GFR at diagnosis were 2.80 mg/dL (IQR 3.17-5.57) and 25 ml/min/1.73m2 (IQR 13-40) respectively. Median involved free light chain (FLC) was 819 mg/L (IQR 130-2870), and difference in FLC 433 mg/L (IQR 85-1022). All pts had abnormal serum free light chains and 25 (73.5%) pts had kappa R-MIDD. Median bone marrow plasma cells percentage was 19% (IQR 10-38%). The most common cytogenetic abnormality was del 13 in 6/25 pts (24.0%). A concurrent diagnosis of myeloma was presented in 10 (32.3%) pts. Pts underwent a median of 2 lines of treatment (IQR 1-2). Median follow-up was 5.95 years (range 0.27 - 22.3 years). Pts were treated at induction with the following therapies: Group 1) immunomodulatory drug (IMiD) +/- bortezomib (Bor) (8/34, 23.5%); Group 2) Bor without IMiD (24/34, 70.6%) or Group 3) other (2/34, 5.9%). Autologous stem cell transplant (ASCT) was performed in 82.4% of pts. The 3- and 6-month hematologic response of ≥VGPR was 30.4% (7/23) and 55.6% (15/27) respectively. At the 6-month, Group 1, 2 and 3 had a ≥VGPR of 14.3%, 26.3% and 100% respectively though Group 3 only had 2 pts. Of the 29 pts assessed for best renal response, 9 pts (31.0%) had a renal response. Best renal response for group 1, 2, and 3 occurred in 0%, 38.1% and 100% of pts, respectively. Median TTNT was 2.9 years. Of 34 pts, only 5 died and median overall survival was not reached (Fig.1A). Improved median OS was associated with diagnosis after 2010 v ≤2010 (p=0.1) (Fig. 1B), >60 years old at diagnosis v ≤60 (p=0.1) (Fig. 1C) and treatment with ASCT (p=0.058) (Fig. 1D), though none met statistical significance. Renal progression occurred in 63.3% pts with median TTRP of 1.8 years. Dialysis dependence occurred in 33.3% pts with median TTD not reached (Fig. 2A). TTD did not differ significantly for pts diagnosed >2010 v ≤2010 (p=0.9) (Fig. 2B), ASCT (p=0.7) (Fig. 2D) though was better for pts who were diagnosed >age 60 vs ≤60 (p=0.027) (Fig. 2C). Five pts had a renal allograft, 3 of whom received the allograft after chemotherapy initiation, with 1 graft failure. In a landmark analysis at 6 months, OS and TTRP was better in pts with ≥VGPR compared to <VGPR, though both did not meet statistical significance (p=0.3 and p=0.2, respectively) (data not shown). No significant difference between ≥VGPR compared <VGPR was observed in TTD (p=0.5) (data not shown). CONCLUSION: In this limited retrospective study, we showed that R-MIDD pts were diagnosed late in the disease when pts already developed severe CKD. R-MIDD pts frequently had a concomitant diagnosis of multiple myeloma. Despite treatment with novel agents and ASCT, only a third of pts had a renal response and a third of pts required eventual dialysis. This study highlights the need for early diagnosis of R-MIDD and better treatments for this disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of HIV Infection on Clinical Characteristics and Treatment Outcomes in African-American Patients with Multiple Myeloma: - a Retrospective Case-Control Study

Introduction: Although multiple myeloma (MM) is not considered an AIDS-defining malignancy such as certain types of non-Hodgkin lymphoma and Kaposi sarcoma, HIV infection can increase the risk of developing MM at a younger age. However, no robust data demonstrates that HIV infection could affect MM outcomes. Case reports or case series suggest that HIV positive MM has more aggressive biological features, clinical course, and shorter overall survival (Faure I et al, AIDS, 1999; Patra SK et al, J Clin Diagn Res, 2015). Other observational studies also reveal that HIV positive MM involves a younger population and has more extramedullary disease however survival data is yet to be explored (De Groot JJB et al, S Afr Med J, 2017; Giri S et al, Blood, 2018). NYC has only 3% of the US population but has reported nearly 16% of all AIDS cases and the Bronx carries the highest HIV infection rate among all the boroughs (NYC Department of Health and Mental Hygiene, 2021). Based on that, we initiated a retrospective study in a tertiary medical facility in the Bronx to investigate the relationship between HIV infection status and the outcome of MM. Methods: Using the electronic medical record data extraction software, we identified patients older than 18 diagnosed with HIV and MM between April 2009 and April 2022. HIV negative MM patients matched for age and ethnicity were included as control group. We conducted a retrospective chart review collecting demographic, laboratory and clinical characteristics and compared them between HIV positive and negative groups. Outcome data included response to initial therapy, presence of extramedullary disease, need for hospitalization during therapy, infectious complications, progression-free survival (PFS) and overall survival (OS). Statistical analysis was performed using chi-square testing for categorical variables and Mann-Whitney for continuous variables given the size of our sample. Results: A total of 14 patients were identified as HIV positive MM. 12 patients were on antiretroviral therapy, 2 patients were considered "long term non-progressor" who did not require treatment. In HIV positive group, mean CD4 count was 554 (71)cells/µl and mean viral load was 2477 (1634)copies/ml. The mean age on diagnosis was 61.5 years old (range 56-72), 57.1% patients were male (8/14), 100% of patients were African American. 9 had IgG subtype, 2 had IgA subtype, 2 had light chain subtype. International Staging System (ISS) stage 1, 2 and 3 were seen in 14.3% (2/14), 35.7% (5/14), 42.9% (6/14) patients, respectively. In one patient stage was unknown. Adverse risk cytogenetics were seen in 2 out of 13 patients at diagnosis (both were gain 1q). Cytogenetic information was not available in one patient. Mean number of lines of therapy was 2.1 and 8 out of 14 underwent autologous stem cell transplantation. Subsequently, 14 HIV positive patients were compared with 14 age/ethnicity-matched HIV negative patients with multiple myeloma. Median duration of follow up was 24 months (range 3-156) in HIV positive patients and 35 months (range 2-168) in HIV negative patients. No statistically significant differences were seen between the two groups in hemoglobin level, creatinine, calcium, lines of therapy, bone marrow plasma cell percentage, presence of bone lesions, number of lines of therapy, number of patients receiving autologous transplant, infectious complications, and OS (Table 1). HIV positive patients had significantly more extramedullary disease (71.4% vs. 21.7%, p=0.008), were hospitalized more often (78.6% vs 28.6%, p=0.008), had inferior response to induction therapy (21.4% vs 100%, p=0.001) (Table 1) and a shorter PFS (median 62.0 (95% CI, 22.8 to 101.9) months vs median 20.0 (95% CI, 0.0 to 42.3) months, p=0.038) (Figure 1). Conclusion: Our study is the first single-center retrospective study evaluating the outcomes and prognosis of MM in minority patients with HIV infection. Despite well-controlled HIV infection with preserved CD4 counts, suppressed viral load and low risk disease in most HIV positive patients, they had more aggressive clinical course with more extramedullary disease, higher hospitalization rate, inadequate response to induction therapy and a shorter PFS compared with age and ethnicity matched HIV negative controls with multiple myeloma. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retrospective Analysis of Prognostic Factors and Survival in Multiple Myeloma Patients Aged 65 Years or Older at Diagnosis in a Real-Life Setting and a Proposed New Staging System

Introduction: The incidence of multiple myeloma (MM) increases with age. Novel agents provide better treatment results. However, adults >65 years of age are often underrepresented in clinical trials making it difficult to assess treatment outcomes in older patients. Appropriate strategies are necessary and treatment must be individualized in this heterogeneous population. Methods: We retrospectively reviewed the charts of 534 patients diagnosed with MM between January 2010 and January 2020 who presented to our department. One hundred twenty-three of them were aged 65 years or older at diagnosis and were included in the study. Clinical and laboratory data were collected and potential prognostic factors of overall survival (OS) were evaluated by univariate and multivariate analyses. Results: Of 123 patients analyzed 54.5% (67) were male and 45.5% (56) were female. The median age was 71 years and 32.5% of patients were equal or older than 75 years. Median follow-up time was 28 months (1-117). Median OS and progression free survival (PFS) were 46 and 17 months, respectively. Of the patients 63.4% (78) died during the study period. The patients were divided into 3 groups according to age: 65-69 (47 patients, median OS 68 months), 70-74 (36 patients, median OS 45 months) and ≥75 (40 patients, median OS 36 months) years old (p: 0.022). International Staging System (ISS) stage could be defined in 117 patients (19 had ISS I, 40 ISS II and 58 had ISS III disease). Revised ISS (R-ISS) could also be defined in 117 patients (17 R-ISS I, 82 R-ISS II and 18 R-ISS III). Both ISS and R-ISS could not identify statistically significant differences regarding OS and PFS. Chromosomal abnormalities were detected by fluorescence in situ hybridization (FISH) and conventional cytogenetics in 56 and 39 patients respectively. Eleven of 56 patients and 4 of 39 patients had unfavorable genetic features and due to the small number these patients are not included in the survival analyses. Bortezomib based doublet and triplet induction regimens were given in 86% of patients. Univariate analysis revealed that age, hemoglobin, creatinine, calcium, albumin, extramedullary disease and bone marrow plasma cell (BMPC) percentage were strongly associated with OS. Receiver operating curve (ROC) analysis determined the optimal cut-off value of BMPC 26.5%. On multivariate analysis albumin, extramedullary disease and BMPC ratio retained prognostic value. Presence of none, one, two or all three of these factors could identify 4 patient subgroups showing median OS rates of 108, 55, 25 and 12 months, respectively (p: <0.001) (Figure). Conclusions: MM primarily affects older adults. Hence, there is a need for simple and reliable staging systems for elderly MM patients. We propose a prognostic scoring method for outcome incorporating easy to use variables such as albumin, extramedullary disease and BMPC ratio. Hypoalbuminemia (≤ 3.5 g/dl), presence of extramedullary disease and BMPC ratio ≥ 26.5% predicted different OS ratios in the study population. A validation of the score in an independent series of patients is planned. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Validation of the CIBMTR Scoring System in Predicting Early Relapse of Multiple Myeloma Post Autologous Hematopoietic Cell Transplant

Introduction: Despite good initial responses, many multiple myeloma (MM) patients eventually relapse post autologous hematopoietic cell transplant (AHCT). Risk stratification to Identify patients that are at an increased risk of early relapse may influence post-AHCT monitoring and selection of maintenance therapy. Recently, the Center for International Blood and Marrow Transplant Research (CIBMTR) scoring system was introduced as a tool to identify patients at risk of early relapse post-AHCT. The scoring system relies on each patient's albumin level at time of MM diagnosis, bone marrow plasma cell (BMPC) percentage at time of AHCT, and cytogenetic risk profile to classify them into three risk categories. Here, we aimed to test the validity of the CIBMTR scoring system by applying it to our cohort. Methods: We reviewed all patients who underwent AHCT for MM at Cleveland Clinic between 2011-2021, and then identified the patients with available data to be incorporated into the CIBMTR system. As per the scoring system's requirements, points were assigned for the following patient characteristics: 4 points for high risk (HR) cytogenetics, 4 points for BMPC ≥10% at AHCT, 2 points for albumin <3.5 g/dL at diagnosis, 1 point for standard risk (SR) cytogenetics, 0 points for normal cytogenetics, BMPC <10% at AHCT, and albumin ≥3.5 g/dL at diagnosis. Baseline demographic, clinical, and cytogenetic data of the included patients were retrospectively collected by reviewing electronic medical records to compare the three risk groups. Analysis was conducted through multivariate analysis using the Statistical Package for Social Sciences (SPSS), while median overall survival (mOS) and median progression free survival (mPFS) of the three groups were analyzed using GraphPad Prism. Results: A total of 313 patients met inclusion criteria and were included in our study. Our cohort had a median age of 61.7 years at AHCT, a 57.2% male preponderance and a median follow up of 31.9 months. With regards to the CIBMTR scoring system constituents, 106 (33.9%) had HR cytogenetics as compared to 146 (46.6%) with SR and 61 (19.5%) with normal cytogenetics. Albumin ≥3.5 g/dL occurred in 85 (27.2%) while BMPC ≥10% were present in 31 (9.9%). CIMBTR risk score application yielded 191 (61%) patients classified as low risk (score 0-3), 110 (35.2%) patients as intermediate risk (score 4-8), and 12 (3.8%) patients as high risk (score 9-10) of early relapse after AHCT. There were no significant differences between the low-, intermediate and high-risk groups with respect to median age at transplant (61 vs 63.1 vs 62.3%, P=0.1), Gender representation (Males 56.5 vs 60 vs 50%, P=0.7), Ethnicity (White 82.2 vs 86.4 vs 91.7%, P=0.5), median lines of therapy pre-AHCT (P=0.3), or remission status (partial/very good partial/complete) pre-AHCT (P=0.17). Compared to low- and intermediate-risk patients, respectively, patients belonging to the high-risk group had higher 1-year relapse (41.7 vs 10.5 vs 18.2%, P=0.0043), 2-year relapse (58.3 vs 17.8 vs 38.2%, P=0.0001) and 3-year relapse (66.7 vs 25.7 vs 50.9%, P<0.0001) rates. Kaplan-Meier based survival analysis confirmed a lower mPFS in the high-risk group compared to the low- and intermediate-risk groups, respectively (14.7 vs 67.7 vs 29 months, P<0.0001) (Fig 1A). Interestingly, the CIBMTR score also distinguished the three risk groups with respect to overall survival. High-risk patients had higher mortality at the 5-year (50 vs 15.7 vs 22.7%, P=0.0082) and 7-year (58.3 vs 17.3 vs 29%, P=0.0008) follow up intervals as compared to low- and intermediate-risk patients, respectively. Kaplan-Meier analysis further corroborated the mortality rates since high-risk patients had lower mOS relative to intermediate- and low-risk patients, respectively (56.6 vs 68 vs unreached, P=0.0046) (Fig 1B). Conclusion: We validated the CIBTMR scoring system criteria within an internal cohort, demonstrating that this system is a reliable tool for identification of patients with a higher risk of early relapse post-AHCT. We further identified differences between risk groups in mortality at 5- and 7-years following AHCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Imaging CXCR4 receptors expression for staging multiple myeloma by using 68Ga-Pentixafor PET/CT: comparison with 18F-FDG PET/CT.

68Ga-Pentixafor positron emission tomography (PET) imaging targets CXCR4 expression which is overexpressed in multiple myeloma (MM). In this study, we evaluated the diagnostic utility of 68Ga-Pentixafor PET/CT for imaging CXCR4 expression in MM and compared results with 18F-fluorodeoxyglucose (18F-FDG) PET/CT. 34 (21M; 13F; median age = 57.5 years) treatment naive multiple myeloma patients were recruited. All the patients underwent 18F-FDG PET/CT and 68Ga-Pentixafor PET/CT imaging. Freshly prepared 68Ga-Pentixafor (148-185 MBq) was injected intravenously and whole-body PET/CT (low-dose CT) was acquired at 1 h post-injection. The pattern of uptake (diffuse, focal or mixed) and the mean SUVmax value of all the lesions (when lesions were ≤5) or of the five most tracer avid lesions (when lesions was >5) were evaluated. Tumor to background ratio (TBRmax) was calculated for both the tracers. Durie Salmon plus staging (DSPS) was used for disease staging on PET and the results were compared with International staging system (ISS). 68Ga-Pentixafor PET/CT showed higher disease extent than seen on 18F-FDG PET/CT in 23/34 patients (68.0%), lesser disease extent in 2/34 (6%) and similar disease extent in 9/34 (26%) patients. Significantly (p < 0.001) higher TBRmax values (5.7; IQR 8.8) were observed on 68Ga-Pentixafor PET/CT as compared to 18F-FDG PET/CT values (2.9; IQR = 4.0). Both the techniques detected extramedullary lesions in six patients. On the other hand, 68Ga-Pentixafor detected medullary lesions in five, whereas, 18F-FDG PET in three patients. Further, only 68Ga-Pentixafor TBRmax correlated significantly (ρ = 0.421; 0.013) with bone marrow plasma cell percentage. 68Ga-Pentixafor PET upstaged more number (9/29) of patients as compared to (4/29) 18F-FDG PET imaging. On the other hand, 18F-FDG PET down-staged 9/29, whereas 68Ga-Pentixafor PET downstaged only 3/29 patients. 68Ga-Pentixafor PET/CT evaluated the whole-body disease burden of CXCR4 receptors non-invasively which is not possible by tissue sampling methods. This novel PET tracer has also implication for disease staging. Dual 68Ga-Pentixafor/18F-FDG PET/CT imaging may help in determining the tumor heterogeneity in MM. This CXCR4 targeting PET tracer has a promising role in the development of CXCR4 targeting theranostics and also for response assessment to these therapies including the conventional treatment.

P886: AFRICAN AMERICAN PATIENTS WITH SMOLDERING MULTIPLE MYELOMA MAY HAVE A LOWER RISK OF PROGRESSION COMPARED TO WHITE PATIENTS

Background: The incidence of multiple myeloma (MM) and its precursor stages is two to threefold higher in African Americans (AAs) compared to whites when adjusted for socioeconomic status, age, and sex. However, there is limited information on whether racial background affects the risk of progression from smoldering MM (SMM) to MM. Aims: To assess the effect of race on the progression from SMM to MM. Methods: Patients with SMM presenting to Memorial Sloan Kettering Cancer Center between the years 2000 and 2019 and who identified as either AA or white were included in this retrospective study. Baseline patient and disease characteristics were collected at the time of diagnosis including laboratory, imaging, and pathology reports. Differences in distributions of continuous and discrete characteristics were assessed by Kruskal-Wallis and chi-square tests. Time to progression (TTP) was assessed using the Kaplan-Meier method with log-rank test for comparisons. Univariate and multivariate Cox proportional hazard models were used to estimate effects of risk factors on TTP with hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 576 patients were included (70 were AA, 12%). Median follow-up time was 3 years in AAs and 4 years in whites. Differences in baseline characteristics between AAs and whites included median age (60 years in AAs [IQR 51-67] vs 64 years in whites [IQR 56-72], p = 0.01), median hemoglobin level (12.3g/dL in AA [IQR 11.8-13] vs 12.8g/dL in whites [IQR 11.8-13.9], p = 0.02), and immunoparesis including 1 or 2 uninvolved immunoglobulins (31% and 10% in AAs vs 56% and 27% in whites, p = 0.002). There was no difference in bone marrow plasma cell percentage (BMPC), M-spike, free light chain ratio, or Mayo-2018 SMM risk score. AA race was associated with a significantly decreased risk of progression in the univariate model (HR 0.57, CI 0.34-0.94). In the multivariate model adjusting for age, sex, and variables associated with an increased risk of progression in the univariate model (BMPC, M-spike, free light chain ratio, immunoparesis and low albumin), AA race remained associated with a decreased risk of progression (HR 0.39, CI 0.16-0.95). Overall, AA patients with SMM had a significantly (p = 0.027) longer median TTP (9.7 vs 6.2 years), and a lower 2-year (12.6% vs 20.1%) and 5-year (34% vs 44.6%) progression rate than whites. Because AA patients were younger at diagnosis, we stratified patients by age group, < 65 vs ≥65 years. In patients < 65 years, there was no difference in progression rate. In patients aged ≥65 years, AA patients continued to have a longer TTP than whites (9.8 vs 5.2 years, p = 0.02). Image:Summary/Conclusion: In our retrospective single institution experience, AA patients with SMM had a lower risk of progression to MM compared to whites. Both groups had similar Mayo-2018 risk scores, however, AA patients had a lower degree of immunoparesis at baseline. Future studies are needed to better understand if these differences are explained by differences in disease biology including genomic mechanisms, immune microenvironment, and systemic immune response.

Generalised autonomic failure as a prognostic factor in systemic light-chain (AL) amyloidosis

Background In the present study, it was investigated whether autonomic dysfunction could predict prognosis in light-chain (AL) amyloidosis patients. Patients and methods Seventy-two patients with biopsy-proven AL amyloidosis were included and underwent an autonomic function test (AFT) between January 2016 and June 2019. Autonomic failure was evaluated using the Composite Autonomic Severity Score (CASS). Survival curves and the three-year overall survival (OS) rate were estimated using the Kaplan–Meier curve, and the Cox proportional hazards regression method was used to evaluate the variables that influenced survival. Results Autonomic dysfunction was observed in 69 (96%) patients with AL amyloidosis, and the three-year OS rate was 67%. Generalised autonomic failure (GAF) was observed in 31 (43%) patients. In the Kaplan–Meier curve, the three-year OS rates in patients with sudomotor dysfunction or GAF were lower than that in control patients (35 vs. 84%, and 33 vs. 81%, respectively). In Cox proportional hazards regression model, female, bone marrow plasma cell percentage, left ventricular systolic dysfunction, and GAF were significant independent variables associated with survival. Conclusion The results of this study indicate that GAF on the AFT is an independent adverse prognostic factor for survival in AL amyloidosis patients.

PVR (CD155) Expression as a Potential Prognostic Marker in Multiple Myeloma.

Poliovirus receptor (PVR, CD155) is upregulated during tumor progression, and PVR expression is associated with poor prognosis in cancer patients; however, prognostic implications for PVR in multiple myeloma (MM) have not been investigated. PVR plays an immunomodulatory role by interacting with CD226, CD96, and TIGIT. TIGIT is a checkpoint inhibitory receptor that can limit adaptive and innate immunity, and it binds to PVR with the highest affinity. We used immunohistochemistry, ELISA, qPCR, and flow cytometry to investigate the role of PVR in MM. PVR was highly expressed in patients with MM, and membrane PVR expression showed a significant correlation with soluble PVR levels. PVR expression was significantly associated with the Revised-International Staging System stage, presence of extramedullary plasmacytoma and bone lesion, percentage of bone marrow plasma cells (BMPCs), and β2-microglobulin levels, suggesting a possible role in advanced stages and metastasis. Furthermore, TIGIT expression was significantly correlated with the percentage of BMPCs. Patients with high PVR expression had significantly shorter overall and progression-free survival, and PVR expression was identified as an independent prognostic factor for poor MM survival. These findings indicate that PVR expression is associated with MM stage and poor prognosis, and is a potential prognostic marker for MM.

Comparison of [18F]fluciclovine and [18F]FDG PET/CT in Newly Diagnosed Multiple Myeloma Patients

Purpose[18F]FDG PET/CT in multiple myeloma (MM) is currently the best technology to demonstrate patchy and extramedullary disease. However, [18F]FDG PET has some limitations, and imaging with alternative tracers should be explored. In this study, we aimed to evaluate the performance of [18F]fluciclovine PET compared to [18F]FDG PET in newly diagnosed MM patients.ProceduresThirteen newly diagnosed transplant eligible MM patients were imaged both with [18F]FDG PET/CT and [18F]fluciclovine PET/CT within 1 week in a prospective study. The subjects were visually assessed positive or negative for disease. The number of lesions and the SUVmax of selected lesions were measured for both tracers. Furthermore, tracer uptake ratios were obtained by dividing lesion SUVmax by blood or bone marrow SUVmax. Between-group differences and correlations were assessed with paired t-tests and Pearson tests. Bone marrow SUVs were compared to bone marrow plasma cell percentage in biopsy samples.ResultsNine subjects were assessed positively by [18F]FDG PET (69%) and 12 positives by [18F]fluciclovine PET (92%). All positive subjects had [18F]fluciclovine scans that were qualitatively scored as easier to interpret visually than the [18F]FDG scans. The number of lesions was also higher; seven of nine subjects with distinct hot spots on [18F]fluciclovine PET had fewer or no visible lesions on [18F]FDG PET. The mean lesion SUVmax values were 8.2 and 3.8 for [18F]fluciclovine and [18F]FDG, respectively. The mean tumour to blood values were 6.4 and 2.0 for [18F]fluciclovine and [18F]FDG, and the mean ratios between tumour and bone marrow were 2.1 and 1.5 for [18F]fluciclovine and [18F]FDG. The lesion SUVmax and ratios were significantly higher for [18F]fluciclovine (all p < 0.01).Local [18F]fluciclovine SUVmax or SUVmean values in os ilium and the percentage of plasma cells in bone marrow biopsies were linearly correlated (p = 0.048). There were no significant correlations between [18F]FDG SUVs and plasma cells (p = 0.82).ConclusionsBased on this pilot study, [18F]fluciclovine is a promising tracer for MM. The visual and semi-quantitative evaluations indicate that [18F]fluciclovine PET/CT can out-perform [18F]FDG PET/CT at diagnosis.