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This study of patients with multiple myeloma found care disparities by race, insurance type, and treatment facility.

•Even though most patients in our study did not meet the eligibility criteria for the MajesTEC-1 trial, teclistamab was safe and effective in this real-world population.•Teclistamab yielded early and deep responses in heavily pretreated patients with relapsed/refractory multiple myeloma, including those with high-risk disease features and prior BCMA-directed therapies.•Extramedullary disease and poor performance status were associated with inferior best overall response rate and progression-free survival.•The incidence of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was low, although the risk of cytopenias and related infections remained an ongoing challenge.

•Frailty, as measured by age, performance status, and organ function, is a better determinant of post-CAR-T outcomes than age alone.•Frail patients treated with CAR-T have inferior efficacy and similar safety outcomes compared to nonfrail patients.

Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for clinicians across practice settings. There is, however, a reason for optimism with the advent of new combination therapy approaches and novel targets offering the promise of improvement in end organ function, survival, and quality of life. This review offers a clinically applicable overview of an approach to diagnosis, risk stratification, and clinical management of AL amyloidosis in an era of rapid therapeutic innovation.

ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen. Key secondary endpoints were response rate and duration of response. Grade ≥3 adverse events were reported in 38 (88.0%) of patients. Cytokine release syndrome was observed in 24 patients (55.8%), with 1 grade ≥3 event (2.3%) and neurotoxicity in 6 patients (14%), with no grade ≥3 events. Infections occurred in 23 patients (53.5%), with 10 (23.3%) of grade ≥3. Overall, 24 patients (55.8%) had a response. Among patients treated with 320 × 106CAR+T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n= 24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3 months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma.

Recently there has been a growing interest in evaluating body composition as a marker for prognosis in cancer patients. The association of body composition parameters and outcomes has not been deeply investigated in patients with autologous hematopoietic stem cell transplantation (HSCT) recipients with non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of 264 NHL patients who received autologous HSCT. PreHSCT abdominal CT scans at the levels of L3 were assessed for body composition measures. We evaluated sarcopenia, myosteatosis, high visceral adipose tissue (VAT) and high visceral adipose tissue density (VATD). Using multivariable Cox proportional regression, we analyzed the association of clinical and transplant-related characteristics with overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM). In a multivariate regression model, patients with higher VATD had worse OS (HR 1.78; 95% confidence intervals CI 1.08–2.95, p= 0.02) and worse NRM (HR 2.31 95% CI 1.08–4.95, p= 0.02) than with lower VATD. Patients with lower levels of VAT also had worse RFS (HR 1.49 95% CI 1.03–2.15, p= 0.03). Sarcopenia and myosteatosis were not associated with outcomes. High pre-transplant VATD was associated with lower OS and higher NRM, and low pre-transplant VAT was associated with worse RFS in patients with NHL undergoing autologous HSCT.

Although venous thromboembolism (VTE) is an important treatment and disease-related complication in myeloma, a validated risk prediction model including disease-specific variables such as cytogenetics or tumor burden is lacking. The aim of this study was to develop a new risk prediction model for VTE in the context of modern antimyeloma therapy. All consecutive patients diagnosed at the Cleveland Clinic between 2008 and 2018 and with available data on baseline candidate risk factors constituted the derivation cohort. The primary outcome was VTE (deep venous thrombosis/pulmonary embolism) within 1 year of treatment initiation. A multivariable model was used, and weights were derived from subdistribution hazard ratios to construct a risk score. The model was validated both by internal bootstrap validation and in an external validation cohort. The derivation cohort consisted of 783 patients. A 5-component risk prediction tool, named the PRISM score, was developed, including the following variables: prior VTE, prior surgery, immunomodulatory drug use, abnormal metaphase cytogenetics, and Black race. The c-statistic of the model was 0.622 (95% confidence interval [CI], 0.567-0.674). The model stratified patients into low, intermediate, and high risk, with 12-month cumulative VTE incidence of 2.7%, 10.8%, and 36.5%, respectively. Risk of VTE increased significantly with increasing score in both the derivation and the external validation data sets, with a subdistribution hazard ratio per 1-point increase of 1.28 (95% CI, 1.19-1.39; P < .001) and 1.23 (95% CI, 1.07-1.41; P = .004) respectively. Although the PRISM score can guide clinicians in identifying patients at a high risk of VTE, additional external validation is necessary for incorporation into routine clinical practice.

•Abnormal metaphase cytogenetics is a predictor of VTE within 12 months in newly diagnosed myeloma.•The PRISM score can identify patients at a high risk of VTE in clinical practice and for designing thromboprophylaxis trials in myeloma.

Despite promising efficacy and safety profiles of BCMA-directed cellular therapies (BDCT) for multiple myeloma (MM), limited access is a challenge. This survey gains insights into the practices and perspectives of oncologists from BDCT-referring and treating centers and identify potential areas of improvement.

Bispecific antibodies (BsAbs) have shown reasonable safety and efficacy for patients (pts) with heavily pre-treated relapsed refractory multiple myeloma (RRMM). However, cytopenias, hypogammaglobulinemia, and infections associated with BsAbs can be prolonged, persistent, and challenging complications of this therapy. This systematic review of clinical trials focuses on cytopenias, hypogammaglobulinemia, and infections associated with BsAbs.

With a median age at diagnosis of 69 years, multiple myeloma (MM) primarily affects elderly patients of which many have been excluded from clinical trials evaluating CAR T-cell therapy. It has been shown that chronologic age alone should not be a barrier towards effective treatments including stem cell transplant and CAR T and that instead of age, frailty scores should be incorporated into CAR T screening assessments. As there is limited literature on safety and efficacy of CAR T-cell therapy in frail patients, we retrospectively evaluated clinical characteristics and outcomes of frail patients with relapsed/refractory MM who received CAR T-cell therapy.

The US Food and Drug Administration implemented a Risk Evaluation and Mitigation Strategy/REMS program for all currently approved BCMA and CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies to mitigate the risks of CRS and ICANS by requiring patients (pts) to stay in proximity of the authorized treating center (ATC) for a period of 4 weeks. Relocation and long monitoring period may present a potential financial challenge and increase disparities in access. Defining the optimal duration of monitoring after treatment, has not been described previously. We therefore evaluated real-world safety outcomes of BCMA and CD-19 CAR-T recipients for multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

Ide-cel is a BCMA-directed CART therapy approved for RRMM based on the KarMMa-1 (KM1) trial. However, patients (pts) with significant comorbidities, poor performance status (PS), aggressive disease, and prior BCMA-directed therapy (BDT) were excluded from KM1. There is an unmet need, therefore, to characterize outcomes in this real-world population. Here, we evaluated outcomes of pts not meeting the KM1 eligibility criteria treated with standard of care (SOC) ide-cel.

Extramedullary disease (EMD) is an aggressive presentation of multiple myeloma (MM) and considered as a risk factor for poor response to therapy. In recent years, novel BCMA-directed therapies (BDT), including CAR T-cell therapies and the bispecific antibody, teclistamab (Tec), have shown impressive efficacy in heavily pre-treated relapse/refractory MM (RRMM). However, there is limited real-world data available on efficacy and safety of BDT in treating EMD.

Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS).

Management of rare hematological disorders pose unique diagnostic and therapeutic challenges due to unusual occurrence and limited treatment options. We retrospectively identified 45 patients receiving matched related donor transplant for rare hematological disorders from 2006 to 2019. Patients were divided into two groups (1) malignant and (2) non malignant. The malignant disorder group included four patients while the nonmalignant group included 41 patients divided into immune dysregulation (n= 23), bone marrow failure (n= 10), metabolic (n= 5), and bleeding diathesis (n= 3). Twenty-six (57.8%) patients received myeloablative conditioning (MAC) and 16 (35.6%) received reduced intensity conditioning (RIC), while 3 (6.6%) patients with severe combined immunodeficiency received stem cell infusion alone without conditioning. The cumulative incidence (CI) of grade II–IV acute GVHD (aGVHD) was 39.1% (n= 18) and chronic GVHD (cGVHD) 15.2% (n= 7). There was no primary graft failure while CI of secondary graft failure was 9%. Overall survival (OS) and disease-free survival (DFS) was 82.2% and 77.8% respectively. Group wise OS was 75% in the malignant group, 82.6% in the immune dysregulation group, 80% in patients with metabolic disorders and bone marrow failure, while 100% in patients with bleeding diathesis. This retrospective analysis shows that hematopoietic stem cell transplant can be a feasible treatment option for rare hematological disorders.

Our study aimed to identify the impact of neighborhood disadvantage level on survival outcomes of recipients of CAR T-cell therapy as this has not yet been described.

Teclistamab is a BCMA-directed bispecific antibody approved for relapsed-refractory multiple myeloma (RRMM) on the basis of the MajesTEC-1 trial. The goal of our study was to report clinical outcomes with teclistamab in a real-world RRMM population.

•Barriers perceived by treating/referring oncologists TO/RO for CART and TCE differ.•Financial burden was the top barrier to access identified by RO for both CART and TCE.•Limited slot availability was the top barrier to CART access identified by TO.•Hospitalization requirements were the top barrier to TCE access identified by TO.•Opportunities needed to raise RO awareness about financial support for CART/ TCE.

•We explored the impact of ALC on the survival outcomes of myeloma patients treated with commercial idecabtagene vicleucel.•We created a new ALC profile and included 3 groups: Normal pre-lymphodepletion (LD) ALC, low pre-LD ALC + percent reduction (%R) from pre-apheresis to pre-LD of <37.5 and low pre-LD ALC + %R ≥37.5.•Low pre-LD ALC with high %R from pre-apheresis to pre-LD was associated with inferior survival outcomes.

•New-onset CRS/ICANS are rare after two weeks from ide-cel and cilta-cel infusion.•Early NRM (<30 days) is driven by IEC-HS and infection.•Late NRM (30-90 days) is driven by infection.•A flexible REMS monitoring period partnering with local oncologists may be safe.

The overall incidence of Clostridium diffi cileinfection (CDI) at the authors’ institution was 9.4%. Longer length of stay and use of greater than four lines of antibiotics were identifi ed as risk factors. Only two of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after hematopoietic stem cell transplantation. No patient suffered from toxic megacolon or ileus or underwent colectomy, and there was no mortality associated with CDI.

Introduction:Multiple myeloma (MM) is a disease of the elderly with a median age of 69 years at diagnosis. In addition to advanced age, many of these patients are frail with pre-existing comorbidities and have been historically excluded from clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory (RR) MM. It has been shown that chronologic age alone should not be a barrier towards effective treatment modalities including stem cell transplant and CAR T and that instead of age, frailty scores should be incorporated into CAR T screening and eligibility assessments. As there is limited literature on safety and efficacy of CAR T-cell therapy in frail patients, we conducted a multi-center retrospective study to evaluate clinical characteristics and outcomes of frail patients with RRMM who received standard of care CAR T-cell therapy in real-world practice.

Introduction

Background:Studies reporting disparities inmultiple myeloma (MM) care patterns are mostly limited to Medicare Parts A & B beneficiaries. Moreover, little is known about access to triplet regimens and expensive prescription oral medications such as lenalidomide.

Introduction

Introduction: