The emergence of b-cell maturation antigen (BCMA) targeting immunotherapy in multiple myeloma.

OBJECTIVE: Multiple myeloma, a plasma cell neoplasm is the second most common hematological malignancy in the United States. Despite significant advances in treatment armamentarium over the last decade, multiple myeloma remains an incurable malignancy. B-cell maturation antigen (BCMA) is an antigen expressed on the surface on plasma cells that can be targeted by novel mechanisms of action including antibody-drug conjugates (ADCs), bispecific T-cell engagers, and chimeric antigen receptor (CAR) T-cell therapy. This review summarizes the clinical application and development of approved and investigational immunotherapies targeting BCMA. DATA SOURCES: A search of the PubMed database was conducted using the following search terms: BCMA, CAR T, myeloma, belantamab mafodotin, and bispecific. Ongoing clinical trials, as well as abstracts from ASH and ASCO evaluating the efficacy and safety of novel agents targeting BCMA were evaluated. Prescribing information was also reviewed. DATA SUMMARY: Since the discovery of BCMA as a target for myeloma, researchers have developed antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapies as novel treatment modalities for myeloma patients. Belantamab mafodotin and idecabtagene vicleucel represent currently available therapies and ongoing trials have demonstrated the efficacy and safety of bispecifics and other BCMA targeting therapies. CONCLUSION: BCMA targeting antibody drug conjugates, bispecific T-cell engagers, and CAR T-cell therapies have demonstrated clinical activity in myeloma patients and represent novel therapies in multiple myeloma treatment paradigm.

Newly approved anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Objective: This article summarizes the background, clinical trials, and place in therapy for the first two anti-CD19 monoclonal antibodies that have been recently FDA approved for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Summary: Treatment options are limited for patients that have relapsed after or are ineligible for autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T-cell therapy. Recent novel therapy approvals have started to change management strategies and outcomes for these patients. Two examples of recent FDA approvals are tafasitamab and loncastuximab tesirine, which represent the first anti-CD19 targeting monoclonal antibodies for patients with R/R DLBCL. Tafasitamab was granted accelerated approval in combination with lenalidomide for adult patients with R/R DLBCL after one or more lines of therapy based on the phase 2, L-MIND trial. Loncastuximab tesirine was granted accelerated approval for adult patients with R/R DLBCL after two or more lines of therapy based on the phase 2, LOTIS-2 trial. The place in therapy and sequencing of these agents can present a challenge to prescribers especially in regards to patients being evaluated for CD19 targeting CAR T-cell therapy. Conclusion: Tafasitamab and loncastuximab tesirine are options for use in patients with R/R DLBCL and are welcome additions to the limited therapy options for these patients. Further data is needed to elucidate sequencing and the impact these agents may have on CAR T-cell therapy. Ongoing clinical trials are studying these agents in the upfront setting in combination with other chemoimmunotherapy agents which may further expand treatment options for patients with B-cell lymphomas.

Safety and tolerability of lenalidomide maintenance dosing in patients with multiple myeloma post-autologous stem cell transplant.

BACKGROUND: For transplant-eligible newly diagnosed multiple myeloma patients, autologous hematopoietic stem cell transplant followed by maintenance lenalidomide is a standard of care practice. Maintenance lenalidomide dosing practices vary amongst physicians and current literature lacks comparisons on intermittent versus continuous dosing. In this retrospective study, we compared the safety, tolerability, and efficacy of continuous versus intermittent lenalidomide dosing. METHODS: This single-center, retrospective review included 72 patients with multiple myeloma receiving lenalidomide maintenance between 2018 and 2021. The primary objective was to determine the incidence of dose modification, defined as any dosage reduction, delay in treatment, or discontinuation of therapy. The secondary objectives were to determine the incidence of hematological and non-hematological toxicities between the two groups. RESULTS: A total of 58 patients in the continuous group and 14 patients in the intermittent group were included. Fifty-four percent of patients in the continuous group required dose modification versus 30% in the intermittent group. Patients who received continuous dosing appeared to have a higher incidence of adverse events when compared to intermittent dosing with the most common adverse events being neutropenia, fatigue, and rash. Twenty-four patients in the continuous group switched to an intermittent schedule after an adverse event. Of these patients, only 8% required further dose modification. CONCLUSION: The higher incidence of lenalidomide dose modifications in the continuous arm suggests that a majority of patients are not able to tolerate continuous lenalidomide maintenance. A more tolerable option for maintenance may be an intermittent schedule, as reflected by the favorable safety outcomes in this group.

Long range order and two-fluid behavior in heavy electron materials.

The heavy electron Kondo liquid is an emergent state of condensed matter that displays universal behavior independent of material details. Properties of the heavy electron liquid are best probed by NMR Knight shift measurements, which provide a direct measure of the behavior of the heavy electron liquid that emerges below the Kondo lattice coherence temperature as the lattice of local moments hybridizes with the background conduction electrons. Because the transfer of spectral weight between the localized and itinerant electronic degrees of freedom is gradual, the Kondo liquid typically coexists with the local moment component until the material orders at low temperatures. The two-fluid formula captures this behavior in a broad range of materials in the paramagnetic state. In order to investigate two-fluid behavior and the onset and physical origin of different long range ordered ground states in heavy electron materials, we have extended Knight shift measurements to URu(2)Si(2), CeIrIn(5), and CeRhIn(5). In CeRhIn(5) we find that the antiferromagnetic order is preceded by a relocalization of the Kondo liquid, providing independent evidence for a local moment origin of antiferromagnetism. In URu(2)Si(2) the hidden order is shown to emerge directly from the Kondo liquid and so is not associated with local moment physics. Our results imply that the nature of the ground state is strongly coupled with the hybridization in the Kondo lattice in agreement with phase diagram proposed by Yang and Pines.

Polatuzumab Vedotin for the Front-Line Treatment of Diffuse Large B-Cell Lymphoma: A New Standard of Care?

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma in the US. For nearly 2 decades, standard front-line treatment has consisted of chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Numerous trials have unsuccessfully attempted to achieve better outcomes in these patients. Recently, the results of the phase III POLARIX trial were published. This study randomized newly diagnosed DLBCL patients to receive polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) or standard-of-care R-CHOP. The POLARIX trial demonstrated 2-year progression-free survival of 76.7% for pola-R-CHP compared with 70.2% for R-CHOP with comparable safety profiles between the two arms. Based on these results, a new standard of care may be emerging in patients with DLBCL. This article provides a practical approach to managing a newly diagnosed patient with DLBCL.

Risk of Inappropriately Timed Live Vaccination After Pediatric Cardiovascular Surgery.

OBJECTIVE: The American Academy of Pediatrics (AAP), Advisory Committee on Immunization Practices (ACIP), and Centers for Disease Control and Prevention (CDC) recommend delaying live vaccinations up to 11 months after transfusions of certain blood products due to the risk of immunoglobulins decreasing immunization efficacy. Because vaccination schedules recommend live immunizations at 12 months, infants aged 5 to 12 months who undergo cardiac surgery requiring blood products are potentially at risk for improper vaccination. The objective of this study was to identify the risk of inappropriately timed live vaccination in pediatric patients after cardiovascular surgery. METHODS: This single-center, retrospective chart review included 345 patients 5 to 12 months of age who underwent cardiovascular surgery between January 1, 2010, and December 31, 2016. Included patients received packed red blood cells (PRBCs) and/or platelets during the surgical admission and a live vaccine within the first 18 months of life. The primary endpoint was the incidence of live vaccine administration within 7 months of receiving PRBCs and/or platelets. RESULTS: Of the 345 included patients, 67% (n = 230) were inappropriately vaccinated after receiving platelets and/or PRBCs during cardiac surgery. CONCLUSIONS: Infants who undergo cardiac surgery between the ages of 5 and 12 months are at risk for inappropriate live vaccination timing. A clinically significant percentage of pediatric patients who received blood products during a cardiac surgical admission later received live vaccines at times that were inconsistent with AAP, ACIP, and CDC recommendations. Future interventions aimed at educating providers and patients may be warranted.