Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple myeloma.

Various drug classes target B-cell maturation antigen (BCMA) including chimeric antigen receptor T-cell (CAR-T) therapies, bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs). Outcomes with CAR-T and bsAb therapies in multiple myeloma (MM) have been affected by T-cell exhaustion, and abrogated expression/mutation of the BCMA target has been observed with anti-BCMA therapies. Optimal anti-BCMA sequencing strategies are needed to improve long-term clinical outcomes.

Modification of Belantamab Mafodotin Dosing to Balance Efficacy and Tolerability in the DREAMM-7 and DREAMM-8 Trials.

Belantamab mafodotin (belamaf) combined with standard therapies demonstrated significant progression-free survival (PFS) and overall survival benefits in DREAMM-7 and PFS benefit in DREAMM-8 in relapsed/refractory multiple myeloma. Belamaf dose modifications managed adverse events, including belamaf-related ocular events. Ocular events included ocular adverse reactions (eg, dry eyes, photophobia, eye irritation) and protocol-mandated ophthalmic examination findings.

Practical Guidance on Clinical Management of Belantamab Mafodotin-Associated Ocular Events.

Importance: Belantamab mafodotin (belamaf)-containing regimens are effective treatment options for patients with relapsed and/or refractory multiple myeloma. Ocular events are a common adverse effect of belamaf treatment, which can be managed by physicians, following appropriate training, to minimize their impact on the patient.

Objective: To develop clinical recommendations for the identification, monitoring, and management of ocular events associated with belamaf therapy, and guidance for any required dose modification.

A Single-Center Study on Frontline Treatment for Multiple Myeloma Patients With 1q Abnormalities.

Introduction: Chromosome 1q copy gains (with-1q-gain) is a frequently observed genetic abnormality in multiple myeloma (MM) patients. Recent research has demonstrated that 1q gain is a prognostic factor, linked to poorer clinical outcomes.

Methods: This study was conducted at the Princess Margaret Cancer Centre to examine the clinical outcomes of newly diagnosed MM patients' with-1q-gain or without-1q-gain abnormality.

Minimal Residual Disease Testing Infrastructure in Multiple Myeloma: Guidance for Clinical Trial and Routine Practice Use in Canada.

Measurable/minimal residual disease (MRD) is 1 of the most powerful prognostic factors for progression-free survival and overall survival in multiple myeloma (MM) and may guide therapeutic approaches. Here, we provide an overview of the current state of MRD testing in MM in Canada, highlighting its current use, approaches, and barriers. Furthermore, we discuss the available MRD assays and address questions on their appropriateness for routine practice and clinical trials.

The clinical journey of belantamab mafodotin in relapsed or refractory multiple myeloma: lessons in drug development.

Patients with relapsed/refractory multiple myeloma (RRMM) have a poor prognosis and a need remains for novel effective therapies. Belantamab mafodotin, an anti-B-cell maturation antigen antibody-drug conjugate, was granted accelerated/conditional approval for patients with RRMM who have received at least 4 prior lines of therapy, based on response rates observed in DREAMM-1/DREAMM-2. Despite the 41% response rate and durable responses observed with belantamab mafodotin in the Phase III confirmatory DREAMM-3 trial, the marketing license for belantamab mafodotin was later withdrawn from US and European markets when the trial did not meet its primary endpoint of superiority for progression-free survival compared with pomalidomide and dexamethasone.

Belantamab mafodotin, pomalidomide, and dexamethasone for triple class exposed/refractory relapsed multiple myeloma: a subgroup analysis of the ALGONQUIN trial.

Given the early use of triplet and quadruplet regimens, most patients with multiple myeloma (MM) will be exposed and/or refractory to PIs, IMiDs, and anti-CD38 mAbs after first- or second-line treatment. Effective treatment for this group of triple class exposed/refractory (TCE/R) patients is crucial. Here we present a post-hoc subgroup analysis of TCE/R patients treated on the ALGONQUIN study of belantamab mafodotin plus pomalidomide-dexamethasone (belamaf-Pd) for relapsed MM.

Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma.

Background: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse.

Methods: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy.

Safety and efficacy of belantamab mafodotin with pembrolizumab in patients with relapsed or refractory multiple myeloma.

Background: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM.

Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial.

Due to evolving treatment standards for newly diagnosed multiple myeloma, many patients will be triple-class exposed after initial relapses and have poor survival. Novel therapies and combinations are therefore required to improve outcomes. B cell maturation antigen (BCMA)-targeted biologics have emerged as an important new area of therapeutics for relapsed multiple myeloma.

Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial.

Multiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy.

The Impact of CD34 Cell Collection Yields for Autologous Transplant on Survival Outcomes in Multiple Myeloma.

Introduction: According to previous data, higher yields of stem-cells collected to support autologous transplantation may predict for improved outcomes. We aimed to assess the association between high stem-cells collection and survival outcomes in multiple myeloma (MM) MATERIALS AND METHODS: We reviewed all patients who underwent autologous transplantation for MM at our center over a 10-year period, and initially used a predefined threshold of 8 × 10/kg used in previous studies.

Results: Six hundred twenty-one patients were analyzed.

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma.

Background: Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.

Methods: In this phase 1-2 study, we administered oral mezigdomide in combination with dexamethasone to patients with relapsed and refractory myeloma.

Single-cell profiling of multiple myeloma reveals molecular response to FGFR3 inhibitor despite clinical progression.

Genomic characterization of cancer has enabled identification of numerous molecular targets, which has led to significant advances in personalized medicine. However, with few exceptions, precision medicine approaches in the plasma cell malignancy multiple myeloma (MM) have had limited success, likely owing to the subclonal nature of molecular targets in this disease. Targeted therapies against FGFR3 have been under development for the past decade in the hopes of targeting aberrant FGFR3 activity in MM.

Post Salvage Therapy Autologous Transplant for Relapsed Myeloma, Ongoing Relevance within Modern Treatment Paradigms?

Background: Salvage transplant has been historically considered effective therapy for myeloma patients relapsing after first transplant, if they achieved adequate remission duration. However, the efficacy of novel agent combinations has called this paradigm into question.

Materials And Methods: We performed a retrospective analysis in a homogeneously treated cohort of 106 patients undergoing ASCT2 at our institution, all of whom received novel agent-based chemotherapy (immunomodulatory agent [IMiD] and/or proteasome inhibitor [PI]) for both induction and relapse.

Antibodies and bispecifics for multiple myeloma: effective effector therapy.

The therapeutic landscape in multiple myeloma (MM) has changed dramatically over the last 2 decades. With the introduction of novel immunotherapies, patients with MM can expect deeper responses, longer remissions, and improved overall survival. Since its approval by the US Food and Drug Administration in 2015, the monoclonal antibody specific for CD38, daratumumab, has been incorporated into both frontline and relapsed treatment regimens.

Kinetics of response to first- and second-line therapies in multiple myeloma: Assessment by both M-spikes and light chains.

Objectives: The prognostic value of kinetics of response to multiple myeloma (MM) therapy is controversial. We aimed to expand the knowledge on this topic by reviewing the kinetics of response to both first- and second-line MM therapy, utilizing a homogeneously treated cohort and analyzing separately both M-spike and light chain (LC) responses for each patient.

Methods: We reviewed all patients who received first-line cyclophosphamide, bortezomib and dexamethasone induction followed by autologous transplant with melphalan and lenalidomide maintenance in our center between 2007 and 2019.

Longitudinal single-cell analysis of a myeloma mouse model identifies subclonal molecular programs associated with progression.

Molecular programs that underlie precursor progression in multiple myeloma are incompletely understood. Here, we report a disease spectrum-spanning, single-cell analysis of the Vκ*MYC myeloma mouse model. Using samples obtained from mice with serologically undetectable disease, we identify malignant cells as early as 30 weeks of age and show that these tumours contain subclonal copy number variations that persist throughout progression.

Fixed duration prolonged duration treatment after first line therapy in patients with systemic light chain amyloidosis.

Background: The main objective of treatment in systemic light chain amyloidosis (AL amyloidosis) is to achieve the best hematological response. Deeper responses are associated with better organ responses and survival. In this study, we analysed the efficacy of prolonged duration treatment after first line in patients with AL amyloidosis.

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study.

Background: On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.