Search

Background and ObjectivesThe relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABAA receptor (GABAAR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABAAR encephalitis in patients with a history of prior aHSCT for MM.MethodsA case series of 3 patients. Anti-GABAAR antibody was tested at the University of Pennsylvania Laboratory.ResultsThe patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABAAR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABAAR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABAAR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement.DiscussionWe highlight the importance of considering anti-GABAAR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.

T cells expressing chimeric antigen receptors have shown remarkable therapeutic activity against different types of cancer. However, their wider use has been hampered by the potential for life-threatening toxicities due to the unintended targeting of healthy cells expressing low levels of the targeted antigen. We have now developed an affinity-tuning approach for the generation of minimally modified, low-affinity antibody variants derived from existing high-affinity antibodies. Using this approach, we engineered low affinity variants of the fully human CD229-specific antibody 2D3. Parental 2D3 originally efficiently targeted multiple myeloma cells but also healthy T cells expressing low levels of CD229. We demonstrate that CAR T cells based on a low affinity variant of 2D3, engineered to also express CJUN to increase CAR T cell expansion, maintain the parental antibody’s anti-tumor activity but lack its targeting of healthy T cells in vitro and in vivo. In addition, we found that low affinity CD229 CAR T cells show reduced trogocytosis potentially augmenting CAR T cell persistence. The fast off-rate CAR produced using our affinity tuning approach eliminates a key liability of CD229 CAR T cells and paves the way for the effective and safe treatment of patients with multiple myeloma and other lymphoid malignancies.One sentence summaryRational T cell engineering yields low affinity CD229 CAR T cells overexpressing CJUN, which maintain the parental cells’ anti-tumor activity but eliminate killing of healthy T cells, increasing CAR T cell expansion, and decreasing trogocytosis.

Key Points A severely immunocompromised patient with MM and COVID19 who received a convalescent plasma product showed SARS-CoV-2 clearance. The convalescent plasma showed humoral immunity against all structural SARS-CoV-2 proteins, which was successfully transferred to the patient.

Background Treatment at academic cancer centers (ACs) has been associated with improved outcomes across hematologic malignancies, including acute myeloid leukemia and non-Hodgkin lymphoma. ACs offer the benefit of high treatment volume in addition to enrollment in clinical trials, involvement in post-graduate education, and expanded access to diagnostic and treatment related services. Though studies on multiple myeloma (MM) have demonstrated a survival benefit with treatment at both high-volume centers and at NCCN designated cancer centers, this is the largest study to date examining the benefit of academic centers. Methods The National Cancer Database was utilized to obtain data on patients diagnosed with MM between 2004-2017 for which data on treatment facility type was available. Using the Commission on Cancer facility categories, patients treated at ACs were compared to those treated at non-academic centers (NACs), including small and large volume community cancer centers. Demographic and treatment characteristics were compared between centers, with median overall survival (OS) assessed by Kaplan Meier. Cox regression analysis was used to asses the HR for OS by facility type, and adjusted on multivariate analysis for age, sex, race, insurance, time to treatment, and use of autologous transplant. Results Of the 179,769 MM patients available, 42.4% were treated at ACs (p 75 years of age were more often treated at NACs (35.6% vs. 20.3%, p The time from diagnosis to treatment was longer at ACs, at 32.4 vs. 26.5 days (p Median OS at ACs was significantly longer than at NACs, with median OS of 67.8 months (95% CI 66.89-68.79 months) compared to 38.6 months (95% CI 38.15-39.13 months) at NACs, p Conclusion Patients with MM had significantly improved survival when treated at academic centers compared to all other facility types. The improvement in OS remained when controlled for available treatment and demographic features. Multiple factors, including specialized care, trial enrollment, and early access to autologous stem cell transplant may contribute to these improvements. Further investigations into the factors contributing to such disparities are required to standardize care and improve overall outcomes. Figure 1 Figure 1. Disclosures Tantravahi: CTI BioPharma: Research Funding; Novartis: Research Funding; BMS: Research Funding; Abbvie Inc.: Research Funding; Karyopharm Therapeutics Inc.: Consultancy, Honoraria, Research Funding. Sborov: SkylineDx: Consultancy; GlaxoSmithKline: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy.

Background The Huntsman Cancer Institute Multiple Myeloma (MM) Program is the primary referral center for the Intermountain West. Over the past 5 years, our Program has experienced a 40% increase in patient volumes, an increase to 4 MM physician providers, and significant expansion of the clinical trial portfolio and clinical/trial support staff. Our previous care model was inefficient and did not optimize the independence of our advanced practice clinicians (APC). Previously, we relied on a traditional “resident model” in which APCs staffed every patient with the attending physician. Our provider group hypothesized that utilizing a more contemporary clinical model would improve clinical efficiency and Relative Value Unit (RVU) generation and enhance job satisfaction for all members of our clinical team while maintaining high patient satisfaction scores. This model, called Project to Improve Volume of Treatment and Satisfaction or PIVOTS, is focused on 4 fundamental pillars including: 1) Modifying physician and APC clinic templates to optimize daily clinic volumes; 2) Establish specific “divisions of labor” for patient follow-up; 3) Standardization of post-autologous transplantation follow-up and disease reassessment; and 4) Standardization of new and return patient clinic notes. The main objective of this project is to fundamentally change our care model to better support our patients and optimize the productivity and moral of our team. Design and implementation Physician templates includes seeing all new patients, follow-up visits with disease reassessments and treatment modification, and per patient request. APC templates shifted to the RCO Model (Revlimid maintenance, Cruising patient, and Outpatient transplant) and acute issue and day 1 treatment visits. Clinic note templates for new, return, and acute patient visits were constructed as a team over the 6 months prior to starting the project Metrics A 12-month period from May 2021 – April 2022 has been specified and the following metrics have been defined pre- and post-PIVOTS implementation. RVU generation will be collected for all providers over this 12-month timeframe and descriptively compared to per provider metrics from the prior 2 years. University Qualtrics and Patient Experience has developed and implemented all job satisfaction surveys that will be completed by all staff (MA, RN, APC, physician) at 3, 6, 9, and 12 months. Patient satisfaction scores and comments are collected per institutional standards. Research productivity for all members of the MM Program will be collected pre- and post-PIVOTS implementation and will include abstract submissions, grant funding, and manuscript production. Results The PIVOTS project will be instrumental in defining a new standard for structuring a dedicated myeloma clinic to improve clinical and academic productivity and job satisfaction without compromising a high-quality patient experience.

Objective To review the current evidence on strategies for selecting the optimal treatment for newly diagnosed patients with multiple myeloma (MM). Data Sources Journal articles, research reports, state of the science papers, and clinical practice guidelines. Conclusion Despite the plethora of drugs to effectively treat MM, the optimal induction regimen for patients with newly diagnosed MM is unknown. Rapid control of the disease, appropriate treatment selection and effective supportive care strategies remain integral to prevention and management of the disease. Strategies for selecting the optimal treatment include considering inherent patient characteristics, frailty, and existing clinical practice guidelines. Implications for Nursing Practice Nurses should provide patients with disease- and treatment-related education to enhance patient and caregiver understanding of the disease and treatment options, taking into consideration clinical data and overarching goals of treatment.

Neurologic manifestations are common in blood diseases, and they can be caused by the hematologic disorder or its treatment. This article discusses hematologic diseases in adult patients, and categorizes them into benign and malignant conditions. The more common benign hematologic diseases associated with neurologic manifestations include anemias, particularly caused by B12 deficiency and sickle cell disease, and a variety of disorders of hemostasis causing bleeding or thrombosis, including thrombotic microangiopathy. Malignant conditions like multiple myeloma, leukemias, and lymphomas can have neurologic complications resulting from direct involvement, or caused by the different therapies to treat these cancers.

Recently, the monoclonal antibody daratumumab was approved as a single agent for the treatment of patients with relapsed/refractory Multiple Myeloma (MM). Daratumumab is an antibody targeting surface molecule CD38 on myeloma cells and the agent is already widely being used based on its good tolerability and proven efficacy. We believe, however, that the efficacy of this drug and other anti-CD38 monoclonal antibodies can be further improved by combining it with other types of immunotherapies. Furthermore, surface molecule CD38 can be used as a target for immunotherapies other than just naked monoclonal antibodies. In this report, we review the expression pattern of CD38 among normal tissues and in different types of plasma cell dyscrasias including their progenitor cells, minimal residual disease, and circulating tumor cells. We summarize the physiological role of CD38 as well as its role in the pathophysiology of MM and we present the most recent clinical trials using CD38 as a target. In addition, we highlight possible combination immunotherapies incorporating anti-CD38 monoclonal antibodies and we demonstrate alternative immunotherapeutic approaches targeting the same antigen such as CD38-specific chimeric antigen receptor (CAR) T cells.

Multiple Myeloma (MM) is a plasma cell (PC) malignancy, which despite significant therapeutic advances, is still considered incurable. This is due to the persistence of chemotherapy-resistant minimal residual disease in the patients' bone marrow (BM) after an effective induction therapy. Immunotherapies targeting surface molecules expressed on the bulk of tumor cells and the chemotherapy-resistant, myeloma-propagating cells could play a central role in this clinical setting. We recently described surface molecule CD229 as a potential therapeutic target for MM. In our current study we assessed the expression of CD229 on different PC subtypes and on cells with a myeloma-propagating phenotype in a total of 77 patients with PC dyscrasias independently at 2 different cancer centers. We found that CD229 was strongly and homogeneously overexpressed on the PC of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, MM, and PC leukemia. CD229 was particularly overexpressed on those PC showing an abnormal phenotype such as expression of CD56. Most importantly, CD229 was also highly expressed on those cells in the patients' BM displaying the phenotype of chemotherapy-resistant and myeloma-propagating cells. In conclusion, our combined findings suggest that immunotherapies targeting CD229 will not only be effective for the bulk of tumor cells but will also help to eradicate chemotherapy-resistant cells remaining in the patients' BM after induction treatment. Hopefully, the design of CD229-specific monoclonal antibodies or chimeric antigen receptor-transduced T cells will help to achieve prolonged remissions or even cures in MM patients.

Over the past decade there have been many advances in the treatment of multiple myeloma (MM). In the first-line setting, induction treatment followed by high-dose chemotherapy plus autologous stem cell transplant (ASCT) is still considered the standard of care for eligible patients. Maintenance therapy has become a mainstay in MM treatment for both transplant-eligible and eineligible patients and, accordingly, a recent study showed that in both groups maintenance treatment with the immunomodulatory drug (IMiD) lenalidomide led to an improved progression-free survival (1). The vast majority of MM patients will eventually suffer a relapse or progression of their disease. Novel therapies such as pomalidomide(POM), a next-generation IMiD approved for patients with relapsed / refractory myeloma (RRM), and carfilzomib have expanded treatment options and increased progression-free survival. Despite the role of new therapies, salvage ASCT remains an effective and useful tool for many patients. Reinduction therapy followed by salvage ASCT should be considered in patients who have responded well to their initial transplant and have had a progression-free interval of at least 12-18 months (2). It is an open question, however, whether patients will derive a similar benefit from consolidation/maintenance (CM) treatment after salvage ASCT as they do in the first-line setting. In this report, we describe the clinical course of 4 consecutive patients who received CM treatment with POM after salvage therapy with high-dose melphalan (HDM) followed by ASCT. Since POM has received FDA-approval for the treatment of patients with RRM, we have placed 4 patients on CM treatment with POM following

Multiple myeloma (MM) is the second most common hematological malignancy and develops from a malignant plasma cell (PC) clone within the human bone marrow (BM). The proliferation and expansion of the malignant PC producing a monoclonal immunoglobulin eventually results in BM failure with anemia, skeletal involvement with osteolytic lesions and hypercalcemia, and renal failure due to the excessive production of paraprotein.1