Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk.

In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]).

Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial.

Background: For patients with newly diagnosed multiple myeloma, reaching minimal residual disease (MRD) negativity after treatment is associated with improved outcomes; however, the use of MRD to modulate therapy remains elusive. We present the final analysis of the MASTER trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) therapy in patients with newly diagnosed multiple myeloma, in which MRD status is used to modulate treatment duration and cessation.

Methods: MASTER was a multicentre, single-arm, phase 2 trial conducted in five academic medical centres in the USA.

Humoral immune reconstitution following therapy with daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd), autologous hematopoietic cell transplantation, and measurable residual disease-response-adapted treatment cessation.

Quadruplet induction, autologous hematopoietic cell transplant (AHCT), and measurable residual disease (MRD) response-adapted consolidation yield an unprecedented depth of response in newly diagnosed multiple myeloma. Patients treated on MASTER (NCT03224507) ceased therapy and entered active surveillance (MRD-SURE) after achieving MRD negativity. This study characterizes quantitative changes in the immunoglobulin (Ig) gene repertoire by next-generation sequencing and serum gamma globulin levels.

High or low? Assessing disease risk in multiple myeloma.

Based upon the development of highly effective therapies such as immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies that target plasma cell biology, a dramatic improvement in overall survival has been observed for most patients with multiple myeloma (MM) over the past 2 decades. Although it is now commonplace for many patients with myeloma to live in excess of 10 years after diagnosis, unfortunately a large subset of patients continues to experience an aggressive disease course marked by substantial morbidity and early mortality. Many clinical biomarkers and staging systems in use today can help with prognostication, but accurate risk assessment can be difficult due to the presence of many different biomarkers with variable prognostic value.

Clinical implications of measurable residual disease assessment in multiple myeloma in the era of quadruplet therapy.

Multiple myeloma is a complex hematological malignancy with substantial heterogeneity in its clinical manifestations, biological processes, and patient outcomes. Although many biomarkers with have been identified to assist with disease monitoring and prognostication, predictive markers that inform treatment decisions remain elusive. As treatments become more effective, assays for measurable residual disease (MRD) below the level of detection of traditional assays have emerged as an essential component of disease assessment with powerful prognostic value for dynamic risk assessment.

Impact of autologous hematopoietic cell transplantation on disease burden quantified by next-generation sequencing in multiple myeloma treated with quadruplet therapy.

The incremental impact of autologous hematopoietic cell transplantation (AHCT) on disease burden with quadruplet induction in newly diagnosed multiple myeloma (NDDM) can be reappraised with the serial assessment of minimal residual disease (MRD). We describe the impact of AHCT on MM burden assessed by next-generation sequencing (NGS) for patients enrolled in a clinical trial utilizing quadruplet induction, AHCT, followed by MRD-adapted consolidation. We describe quantitative changes in MRD burden with AHCT and explore patient and disease features influencing the magnitude of MRD reduction with AHCT.

Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma.

Purpose: The MASTER trial combined daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) in newly diagnosed multiple myeloma (NDMM), using minimal residual disease (MRD) by next-generation sequencing (NGS) to inform the use and duration of Dara-KRd post-autologous hematopoietic cell transplantation (AHCT) and treatment cessation in patients with two consecutive MRD-negative assessments.

Methods: This multicenter, single-arm, phase II trial enrolled patients with NDMM with planed enrichment for high-risk cytogenetic abnormalities (HRCAs). Patients received Dara-KRd induction, AHCT, and Dara-KRd consolidation, according to MRD status.

Progress in the Management of Smoldering Multiple Myeloma.

Purpose Of Review: Smoldering multiple myeloma (SMM) is defined as an asymptomatic clonal proliferation of pre-malignant plasma cells and an increased risk of progression to multiple myeloma (MM) relative to monoclonal gammopathy of undetermined significance. Whether patients with SMM should be treated prior to development of symptomatic disease is fiercely debated and is a highly active area of research.

Recent Findings: The ECOG E3A06 study demonstrated that early treatment with lenalidomide significantly reduced the risk of progression to MM compared to observation in patients with high risk SMM.

Chromosome 1q21 abnormalities in multiple myeloma.

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease.

Gain of Chromosome 1q is associated with early progression in multiple myeloma patients treated with lenalidomide, bortezomib, and dexamethasone.

Gain of chromosome 1q (+1q) is commonly identified in multiple myeloma and has been associated with inferior outcomes. However, the prognostic implication of +1q has not been evaluated in the setting of standard triplet regimens. We retrospectively analyzed 201 consecutive patients with newly diagnosed myeloma who received induction with lenalidomide, bortezomib, and dexamethasone (RVD) and were tested for +1q at diagnosis by fluorescent in-situ hybridization.

Efficacy and Safety of Sorafenib in a Racially Diverse Patient Population with Advanced Hepatocellular Carcinoma.

Background: There are few efficacy and toxicity data on sorafenib for patients treated for hepatocellular carcinoma (HCC) who are not Caucasian or Asian.

Materials And Methods: A retrospective analysis was carried out on 67 patients treated with sorafenib for advanced HCC at an urban referral center. Patients were categorized by race, age, sex, status, stage, and dose.