Efficacy of Selinexor in Relapsed/Refractory Multiple Myeloma (RRMM) Patients with del17p and Other High-Risk Abnormalities (A Retrospective Single-Center Study).

Selinexor (Seli) is a first-in-class, oral selective inhibitor of the nuclear export protein, exportin-1 (XPO1). Seli exhibits its antitumor effect through the blockage of XPO1, which increases nuclear retention of tumor suppressor proteins (TSPs), including p53, thereby limiting the translation of oncogenes, triggering cell cycle arrest and the death of malignant cells. Multiple Myeloma (MM) patients with del17p are deficient in TP53 and have a particularly poor prognosis. Given its unique mechanism of action, we investigated whether Seli has increased efficacy in RRMM patients with del17p compared to other high-risk cytogenetics (OHRC). This is an IRB-approved observational study of RRMM patients with high-risk cytogenetics (del17p, t (4;14), t (14;16) or gain 1q) or standard-risk cytogenetics treated at the Levine Cancer Institute (LCI) with a Seli-based regimen between January 2019 and December 2022. Time-to-event endpoints (PFS, OS) were evaluated using Kaplan-Meier (KM) methods. Log-rank tests compared time-to-event endpoints between cohorts [del17p vs. OHRC vs. standard risk]. We identified 40 RRMM patients with high-risk cytogenetics, including 16 patients with del17p and 24 patients with OHRC, as well as 20 with standard-risk cytogenetics. The median age was 62.5 vs. 69 vs. 65.5 years (del17p group vs. OHRC vs. standard risk). The median prior line of therapies was five (range: 3-16) with similar rates of prior autologous stem cell transplant in all arms (68.8% vs. 62.5% vs. 70.0%). The most frequently used regimens were Seli-Pomalidomide-dexamethasone(dex) or Seli-Carfilzomib-dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. The median time to start the Seli-based regimen after initial MM diagnosis was 5.6 years for the del17p group, 4.1 years in OHRC, and 4.8 years in the standard-risk group. The median follow-up time after the start of the Seli-based regimen was 10.5 months (mos) in the del17p group, 8.4 mos in OHRC, and 10.3 mos in the standard-risk group. In the del17p group, 50% had an objective response, 41.7% in the OHRC, and 35% in the standard-risk group (p = 0.71). Depth of response was also similar across the arms (12.5% vs. 12.5% vs. 10.0% VGPR p = 0.99). The median OS was 10.9 mos in the del17p group, 10.3 mos in the OHRC, and 10.3 mos in the standard-risk group (p = 0.92). The median OS was 15.5 mos for patients who received Seli as a bridging therapy versus 9 mos for Seli use for other reasons rather than as a bridge. Overall, Seli-based regimens showed promising responses even in this heavily pretreated population. Our analysis suggests that Seli-based regimens lead to similar outcomes among RRMM patients with del17p, OHRC, and standard-risk cytogenetics. This contrasts with previously reported outcomes using combinations of novel therapies in this population, where the del17p patients often have a poorer prognosis. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response.

Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13%) patients with RI, including 11 patients severe RI (dialysis, N=1). Patients with RI were older, more likely to be female and had higher likelihood of having Revised International Staging System stage 3 disease. Rates and severity of cytokine release syndrome (89% vs. 84%, grade ≥3: 7% vs. 2%) and immune effector cell-associated neurotoxicity syndrome (23% vs. 20%) were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term grade ≥3 cytopenias, although cytopenias were similar by 3 months following CAR T-cell therapy. Renal function did not worsen after CAR T-cell therapy in patients with RI. Response rates (93% vs. 82%) and survival outcomes (median progression-free survival: 9 vs. 8 months; P=0.26) were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.

Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy.

ABSTRACT: Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

Efficacy and Safety of Daratumumab, Pomalidomide, and Dexamethasone (DPd) Compared to Daratumumab, Bortezomib, and Dexamethasone (DVd) in Daratumumab-Naïve Relapsed Multiple Myeloma.

Daratumumab-based combinations with pomalidomide/dexamethasone (DPd), or bortezomib/dexamethasone (DVd), have shown activity in relapsed/refractory multiple myeloma (RRMM) patients. However, no direct comparisons of safety or efficacy of the two regimens have been published to date. We conducted a retrospective study to compare the safety and efficacy of DPd and DVd in daratumumab-naïve RRMM patients. We included 140 daratumumab-naïve patients who had received DPd or DVd for RRMM. Overall, the DPd group had a greater number of patients who had high-risk disease characteristics. Although response was deeper in the DPd group, the median progression-free survival (PFS) and overall survival (OS) were similar between the two groups. The DPd group exhibited a higher incidence of hematologic toxicities, whereas the DVd group had a higher incidence of peripheral neuropathy. The study results showed that while DPd may provide a deeper response, there was no significant difference in PFS or OS compared to DVd. For the high proportion of difficult-to-treat patients, duration of treatment may have contributed to these results, indicating that patient and disease characteristics should be considered when selecting salvage treatments.

Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: U.S. Myeloma Immunotherapy Consortium real world experience.

While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted CAR T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤ 3 months after CAR T infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤ 3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤ 3 months of infusion (p < 0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (p < 0.001; median PFS for ≥ 3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T who may benefit from specific interventions pre and post CAR T to improve outcomes.

Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy.

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.

Outcomes of Penta-Refractory Multiple Myeloma Patients Treated with or without BCMA-Directed Therapy.

Despite advances in treatment, outcomes remain poor for patients with penta-relapsed refractory multiple myeloma (RRMM). In this retrospective analysis, we evaluated the survival outcomes of penta-RRMM patients treated with (BCMA)- directed therapy (BDT). We identified 78 patients with penta-RRMM. Median age was 65 years, 29 (37%) had R-ISS stage III disease, 63 (81%) had high-risk cytogenetics, and 45 (58%) had extra-medullary disease. Median LOT prior to penta-refractory state was 5 (3-12). Amongst penta-RRMM, 43 (55%) were treated with BDT, 35 (45%) were not treated with BDT. Type of BDT received included belantamab mafadotin 15 (35%), Chimeric Antigen Receptor T-cell therapy 9 (21%), BCMA monoclonal antibody 6 (14%), and Bispecific T-cell engager 2 (5%). Eleven (25%) patients received more than one BDT. No significant differences were identified between baseline characteristics for the two groups. Patients treated with a BDT had better median overall survival, 17 vs. 6 months, HR 0.3 p-value < 0.001. Poor performance status, white race, and high-risk cytogenetics were associated with worse outcomes, whereas using a BDT was associated with better outcomes. Patients with penta-refractory MM have poor outcomes. Our retrospective analysis showed a significant survival benefit using BDT when compared to non-BDT for patients with penta-RRMM.

Bone marrow Ki-67 index is of prognostic value in newly diagnosed multiple myeloma.

BACKGROUND: Ki-67 is an index of proliferative activity and is an established predictive and prognostic marker in multiple malignancies. However, its prognostic relevance in multiple myeloma (MM) is unclear. We investigated the relationship between Ki-67 expression and survival outcomes in MM in the era of novel therapies. METHODS: We interrogated our database to identify patients with MM, newly diagnosed between July 1, 2013 and December 31, 2020, with Ki-67 expression assessed by immunohistochemistry (IHC) on bone marrow biopsies. Using an established threshold of 5% we defined Ki-67low (≤5%) and Ki-67high (>5%) subgroups for association with progression-free survival (PFS) and overall survival (OS). RESULTS: Of 167 patients included: 53 (31.7%) had Ki-67high and 114 had Ki-67low. More patients with R-ISS 3 had Ki-67high (22.2% vs. 9.7%). The gain of 1q21 was overrepresented in the Ki-67high group (28% vs. 8%). Median PFS in the Ki-67low group was 3.1 years, and in the Ki-67high group 1.6 years (log-rank p < .001, HR: 1.9). Median OS was not reached in the Ki-67low vs. 4.8 years in the Ki-67high cohort (HR: 1.9; log-rank test: p = .018). In the multivariable modeling, after adjusting for other risk factors, HR for Ki-67high versus Ki-67low was 2.4 (p < .001) for PFS and 2.1 (p = .026) for OS. CONCLUSIONS: Our results demonstrate that a high Ki-67 index (>5%) is an independent prognostic marker associated with worse OS and PFS in newly diagnosed MM. IHC staining for Ki-67 on bone marrow biopsies could be easily adopted as a prognostic biomarker for MM in economically constrained healthcare settings.

A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse.

INTRODUCTION: Treatment of patients with multiple myeloma (MM) in first relapse remains a challenge. This phase II study combined elotuzumab (Elo) with carfilzomib, lenalidomide, and dexamethasone (KRd) for treatment of MM in first relapse with the aim of improving efficacy. METHODS: Enrolled patients received Elo-KRd induction for 4 cycles, and Elo-lenalidomide maintenance until progression. The primary endpoint was VGPR or better (≥VGPR) postinduction. Secondary endpoints were MRD by flow cytometry, OS, PFS, and safety. Correlatives included characterization of the impact of Elo-KRd on NK and T cell subsets via flow cytometry. Target accrual of 40 patients was not met due to COVID-19 pandemic. RESULTS: Of 15 patients enrolled, 10 (67%) had high-risk features (del17p, t[4;14], t[14;16], 1q gain/amplification, plasma cell leukemia, extramedullary MM, or functional high risk), 12 (80%) were lenalidomide-refractory, and 5 (33.3%) bortezomib-refractory. Postinduction ≥VGPR was 7/15 (46.7%) and MRD-negative (10-5) rate 20%. Overall response during study was 80%, including ≥VGPR as best response of 53.3%. At median follow-up of 28.2 (range, 3.8 to 44.2) months, the median PFS was 11.5 months (95% CI 1.9, 18), and median OS not reached (95% CI 10.1, NA). No new safety concerns were reported. Elo-KRd treatment did not augment NK cell distribution or activity in blood or bone marrow. Effector CD4+ and CD8+ T cells significantly decreased postinduction, with concomitant acquisition of T central memory phenotype, particularly at a high rate in ≥VGPR group. CONCLUSION: A short course of Elo-KRd induction followed by Elo-lenalidomide maintenance demonstrated activity in predominantly lenalidomide-refractory and / or high-risk MM. The results with this well-tolerated combination are comparable to other contemporary approved triplet combinations.

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone.

Background: Daratumumab, pomalidomide, and dexamethasone (DPd) is an effective option for treatment of patients with relapsed/refractory multiple myeloma (RRMM). In this study, we sought to analyze the risk of hematological and non-hematological toxicities in patients who responded to DPd treatment. Methods: We analyzed 97 patients with RRMM who were treated with DPd between January 2015 and June 2022. The patients and disease characteristics, as well as safety and efficacy outcomes were summarized as descriptive analysis. Results: The overall response rate for the entire group was 74% (n = 72). The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common grade III/IV non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%). The incidence of dose reduction/interruption was 76% (55/72), which was due to hematological toxicity in 73% of the cases. The most common reason for discontinuing treatment was disease progression in 61% (44 out of 72 patients). Conclusions: Our study revealed that patients who respond to DPd are at high risk of dose reduction or treatment interruption because of hematological toxicity, typically due to neutropenia and leukopenia leading to increased risk of hospitalization and pneumonia.

Retrospective Review of Outcomes of Multiple Myeloma (MM) Patients With COVID-19 Infection (Two-Center Study).

INTRODUCTION: COVID-19 has profound effects on patients with multiple myeloma (MM) mainly due to underlying immune dysfunction and associated therapies leading to increased susceptibility to infections. The overall risk of morbidity and mortality (M&M) in MM patients due to COVID-19 infection is unclear with various studies suggesting case fatality rate of 22% to 29%. Additionally, most of these studies did not stratify patients by their molecular risk profile. METHODS: Here, we aim to investigate the effects of COVID-19 infection with associated risk factors in MM patients and the effectiveness of newly implemented screening and treatment protocols on outcomes. After obtaining institutional review board approvals from each participating institution, we collected data from MM patients diagnosed with SARS-CoV-2 infection from March 1, 2020, to October 30, 2020, at 2 myeloma centers (Levine Cancer Institute & University of Kansas medical center). RESULTS: We identified a total of 162 MM patients who had COVID-19 infection. The majority of patients were males (57%) with a median age of 64 years. Most patients had an associated comorbid condition. Their myeloma disease status and prior autologous stem cell transplant at the time of infection had no impact on hospitalization or mortality. In univariate analysis, chronic kidney disease, hepatic dysfunction, diabetes, and hypertension were associated with an increased risk of hospitalization. In multivariate analysis regarding survival, increased age and lymphopenia were associated with increased COVID-19-related mortality. CONCLUSION: Our study supports the use of infection mitigation measures in all MM patients, and adjustment of treatment pathways in MM patients diagnosed with COVID-19.

Clinical efficacy of retreatment of daratumumab-based therapy (D2) in daratumumab-refractory multiple myeloma.

Daratumumab demonstrates activity as a single agent and in combination with either immunomodulatory agents (IMiDs) or proteasome inhibitors (PIs) in relapsed refractory multiple myeloma (RRMM). However, little is known about the benefit of daratumumab retreatment in daratumumab-refractory MM. This study aimed to analyze the clinical efficacy of daratumumab-based retreatment (D2) in patients who are daratumumab refractory MM. Retrospectively, we identified 43 RRMM patients from a single-center database review. The median age was 65 years, 42% patients had high-risk cytogenetics, and 23% had an extramedullary disease, while the median time between D2 and prior daratumumab was 1 (0.25-39) month. All D2 patients received combination therapy with either pomalidomide, carfilzomib, bortezomib, or lenalidomide. The response rate, median progression-free, and overall survival were 49%, 7.97 and 32.6 months, respectively. Our study raises the possibility of re-utilizing daratumumab in combination with different classes of anti-myeloma drugs to generate responses in RRMM patients who are daratumumab-refractory.

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium.

PURPOSE: Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label. METHODS: Data were retrospectively collected from patients with RRMM who underwent leukapheresis as of February 28, 2022, at 11 US institutions with intent to receive SOC ide-cel. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines and managed according to each institution's policies. Responses were graded on the basis of the International Myeloma Working Group response criteria. RESULTS: One hundred fifty-nine of 196 leukapheresed patients received ide-cel by data cutoff. One hundred twenty (75%) infused patients would have been ineligible for participation in the KarMMa clinical trial because of comorbidities at the time of leukapheresis. Any grade and grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 82/3% and 18/6%, respectively. Best overall and ≥ complete response rates were 84% and 42%, respectively. At a median follow-up of 6.1 months from chimeric antigen receptor T infusion, the median progression-free survival was 8.5 months (95% CI, 6.5 to not reached) and the median overall survival was 12.5 months (95% CI, 11.3 to not reached). Patients with previous exposure to B-cell maturation antigen-targeted therapy, high-risk cytogenetics, Eastern Cooperative Oncology Group performance status ≥ 2 at lymphodepletion, and younger age had inferior progression-free survival on multivariable analysis. CONCLUSION: The safety and efficacy of ide-cel in patients with RRMM in the SOC setting were comparable with those in the phase II pivotal KarMMa trial despite most patients (75%) not meeting trial eligibility criteria.

Daratumumab, pomalidomide, and dexamethasone (DPd) followed by high dose chemotherapy-Autologous Stem Cell Transplantation leads to superior outcomes when compared to DPd-alone for patients with Relapsed Refractory Multiple Myeloma.

BACKGROUND AND OBJECTIVES: While the role of autologous stem cell transplant (ASCT) in the first line therapy for newly diagnosed multiple myeloma is well established, efficacy of ASCT for patients with relapsed refractory multiple myeloma (RRMM) in the era of novel therapeutic agents remains unknown. In this single center retrospective analysis, we evaluated and compared the efficacy and safety outcomes of patients with RRMM treated with daratumumab pomalidomide dexamethasone (DPd) alone versus (vs) DPd followed by ASCT. METHODS: A total of 83 patients with RRMM who were treated with and achieved at least partial response (PR) with DPd were evaluated by electronic medical records. All patients who responded to DPd and were deemed eligible for ASCT proceeded with high dose melphalan followed by autologous stem cell infusion (DPd + ASCT group). Remaining patients continued DPd until disease progression or intolerable toxicities (DPd-alone group). Responses were evaluated using the International Myeloma Working Group response criteria and toxicities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events. Patient and disease characteristics, as well as efficacy and safety outcomes were summarized using descriptive statistics. Kaplan-Meier analyses were used to estimate progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 21/83 (25%) patients with RRMM who achieved at least PR to DPd underwent ASCT (DPd + ASCT group) while the remaining 62/83 (75%) continued DPd without ASCT (DPd-alone group). For the entire patient population, median age was 66 years (42-81), 49 (59%) patients were male, 54 (65%) patients had IgG isotype, 21 (25%) patients had R-ISS stage III disease, 51 (61%) patients had high-risk cytogenetics, and 17 (20%) patients had extramedullary disease. Patient age, disease stage, cytogenetic risk profile were well balanced between two groups. A stringent complete response was seen in 10 (16%) and 12 (57%) patients in the DPd-alone and DPd + AST groups, respectively. Median PFS was 17.5 months in the DPd-alone vs 42.2 months (p=0.006) in the DPd + ASCT group. Median OS was 38.1 months in the DPd-alone group vs not reached in the DPD + ASCT group (p=0.009). The most common grade 3 or 4 treatment-related adverse events (TRAE) were myelosuppression and gastrointestinal toxicities, more commonly seen in the DPd + ASCT group. No treatment-related mortalities were observed in either group. CONCLUSION: Patients with RRMM who responded to DPd and underwent HDT-ASCT demonstrated superior depth and duration of remission compared to those who received DPd-alone. Although DPd followed by ASCT is associated with more cytopenias and gastrointestinal toxicities, this treatment appears to be overall safe for patients with RRMM.

Standardizing Clinical Workflow for Assessing Minimal Residual Disease by Flow Cytometry in Multiple Myeloma.

INTRODUCTION: Minimal residual disease (MRD) status is an established prognostic biomarker for patients with multiple myeloma. Commonly used MRD testing techniques such as next generation sequencing or next generation flow cytometry can detect as little as one or two multiple myeloma plasma cells in 106 normal bone marrow cells. Early pull of bone marrow aspirates (BMA), necessary to achieve such level of sensitivity, can be difficult to secure in routine clinical practice due to the competing need for early pull samples for clinical response assessment, therefore introducing the risk of analytical interference during MRD testing. METHODS: To overcome this challenge, we standardized our workflow for collecting specimens by using a technical first pull after needle repositioning for MRD testing. To capture a comprehensive picture of MRD assay performance and specimen adequacy, we tested for MRD on 556 technical first pull bone marrow aspirates by next generation flow cytometry. Among the specimens, several key multiple myeloma treatment milestones were represented: end of induction therapy, two to three months post-autologous stem cell transplant, early and late stages of maintenance therapy. RESULTS: By using the technical first pull bone marrow aspirate, we achieved an analytical assay input of 10 million nucleated cells for 97.5% of specimens. Our analytical sensitivity reached 10-6; (i.e., 10 multiple myeloma plasma cells in 10 × 106 bone marrow cells). Twenty-four percent of specimens were significantly hemodiluted. Low assay input or hemodilution quantifiably lowered the assay sensitivity. CONCLUSION: Specimen adequacy is, therefore, an important metric to incorporate into MRD status reporting.

Belantamab in Combination with Dexamethasone in Patients with Triple-class Relapsed/Refractory Multiple Myeloma.

BACKGROUND: Triple-class relapsed/refractory multiple myeloma (RRMM) has a poor prognosis. This study analyzed the clinical outcomes of Belantamab mafadotin in combination with dexamethasone (Bd) in triple-class RRMM. METHODS: We identified 35 patients with triple-class RRMM who received Bd at the University of Kansas from October 2019 to November 2021. RESULTS: The median age was 66 years (42-85) and the median prior lines of therapy was 5 (3-15). Nineteen (54%) patients had R-ISS stage III disease, 15 (43%) patients had high-risk cytogenetics, and 15 patients (43%) had extramedullary disease (EMD). Eight patients received prior BCMA-targeted therapy. Overall response rate (ORR) was 43%, with 23% achieving very good partial response and better. At a median follow up of 10.7 months, the median progression-free survival and survival were 4.9 and 10.7 months, respectively. The most common adverse event was keratopathy, which occurred in 30 (86%) patients. Twenty-four patients required dose reduction or delay due to keratopathy. Other common toxicities included anemia (83%), thrombocytopenia (80%), neutropenia (34%), and elevated liver function tests (51%). CONCLUSION: Our analysis shows Bd has good activity in triple-class RRMM. Keratopathy remains a challenging AE and the leading cause of dose reduction, delay and treatment cessation.

Neutralizing antibody responses against SARS-CoV-2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination.

Many patients with plasma cell disorder (PCD) on active treatment with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require hospitalization, with an increased mortality rate over healthy adults. The FDA approved two mRNA vaccines against SARS-CoV-2: BNT162b2 and mRNA-1273. To assess the efficacy of vaccination in patients with PCD, retrospectively, we identified all patients on active treatment. A total of 149 patients were included. Neutralizing antibodies (NAbs) levels against SARS-CoV-2 adequate, intermediate, and no response were observed in 42%, 32%, and 26%, respectively. Low NAbs were seen in patients on daratumumab combinations or anti-BCMA therapy, low lymphocytes, and low IgG levels. Twenty-three (15%) patients have SARS CoV-2, while 8% required hospitalization, majority of these patients had intermediate or no response based on NAbs levels. Therefore, checking NAbs may be clinically helpful in identifying patients' responses. Further prospective studies should ascertain the value of a third vaccine dose in this population.