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The article focuses on a study on immunophenotypic evidence for reactive polyclonal marrow plasmacytosis. Topics discussed include treatment paradigm for patients with multiple myeloma (MM) receiving lenalidomide maintenance, description of polyclonal Immunoglobulin and free light chain (FLC) elevations, and treatment of patients with induction therapy including lenalidomide and dexamethasone.

We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3–5) and control patients (4 days, range 3–9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients’ clinical course following AHCT in PCM. [ABSTRACT FROM AUTHOR]

Objectives To characterize the effect of three humanized IgG κ monoclonal antibodies (daratumumab, isatuximab, and elotuzumab) on the interpretation of results generated by protein electrophoresis, immunofixation, free light chain, and heavy/light chain assays performed on human serum. Methods Healthy volunteer serum and serum from multiple myeloma patients were supplemented with clinically relevant concentrations of each of the three monoclonal antibodies. These specimens then underwent analysis via serum protein electrophoresis, immunofixation, serum free light chain quantification, heavy/light chain quantification, total IgG, and total protein. In addition, serum specimens from patients who had undergone treatment with elotuzumab for multiple myeloma underwent similar analysis. Results Addition of the study drugs to serum from both the healthy donor as well as multiple myeloma patients resulted in a visible and quantifiable M-protein on SPEP and a visible IgGκ band by IFE. Increases were also noted in total IgG, IgGκ, and IgGκ/IgGλ-ratios. Analysis of serum from multiple myeloma patients receiving study drug showed similar findings with an additional IgGκ band and quantifiable M-protein with similar migration patterns in specimens drawn after administration. Conclusion The treatment of multiple myeloma patients with monoclonal antibodies results in a visible and quantifiable M-protein that has the potential to falsely indicate poor response to therapy. [ABSTRACT FROM AUTHOR]

Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance antimyeloma cellular immunity generated by pomalidomide, leading to improved clinical responses. In this single-center, phase 2 study, 48 patients with relapsed/refractory MM (RRMM) received 28-day cycles of pembrolizumab, 200 mg IV every 2 weeks, pomalidomide 4 mg daily for 21 days, and dexamethasone 40 mg weekly. Patientshadamedianof 3 (range: 2-5) lines of therapy, medianage 64 (range: 35-83) years, and had received both an immune modulatory drug (IMiD) and proteasome inhibitor: (35 [73%]of 48)wererefractorytoboth; (31 [70%])hadreceivedanautologoustransplant, and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3 to 4 occurred in (19 [40%] of 48 patients), including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%]), and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5 [10%]), mostly £ grade 2. Objective responses occurred in (29 [60%] of 48) patients, including stringent complete response/complete response (4 [8%]), very good partial response (9 [19%]), and partial response (16 [33%]);median duration of response was 14.7months. At median follow-up of 15.6months, progression-free survival (PFS)was 17.4months and overall survival was not reached. Analyses of pretreatment marrow samples revealed a trend for increased expression of PD-L1 in responding patients and longer PFS with increased T-lymphocyte infiltrates, irrespective of PD-1 expression. Pembrolizumab, pomalidomide, and low-dose dexamethasone have acceptable safety and durable responses in RRMM patients. [ABSTRACT FROM AUTHOR]

Background High-dose chemotherapy and autologous stem cell transplantation (ASCT) remains the standard-of-care in transplant-eligible patients with multiple myeloma (MM). Bortezomib with lenalidomide and dexamethasone (RVD) is the most common triplet induction regimen for patients with newly diagnosed MM in the US. Carfilzomib with lenalidomide and dexamethasone (KRD), however, has shown promising efficacy and may ultimately supplant RVD. Comparative studies of stem cell collection yields and autograft purity after RVD vs KRD induction have not been performed and merit investigation. Methods Study subjects received RVD or KRD induction therapy at Memorial Sloan Kettering Cancer Center between 2014-2018. Statistical analyses included unpaired t-test, chi-square test, ANOVA, and Fisher's exact test (P value <0.05 = statistically significant). Results Demographics were similar for the 2 cohorts (RVD: 126 patients, KRD: 101 patients) (Fig 1A). Deeper responses (VGPR or better), including bone marrow (BM) minimal residual disease (MRD) negativity by 10-color flow cytometry, were higher with KRD (Fig 1B). Pre-collection BM cellularity, interval from end of induction therapy to start of stem cell collection, and method of stem cell mobilization were similar for the 2 cohorts (Fig 2). Average time to stem cell collection completion (collection target = 10 × 106 CD34+ cells/kg) was slightly greater with KRD (RVD 1.87 vs KRD 2.2 days), as was the fraction of patients requiring ≥3 days to complete collection (RVD 21.4% vs KRD 39.6%) (Fig 2). Viable CD34+ cell content (cells/mcL) was significantly higher with RVD (111.31 vs 63.54, p=0.0019), which associated with higher total stem cell yield after RVD (RVD 11.21 × 106 vs KRD 9.44 × 106, p=0.0245). Collection failure was rare but higher with KRD (4 patients, 3.96%) than with RVD (1 patient, 0.8%) (p=0.17). Advanced age (≥70) was a common factor predictive of lower stem cell yields for both cohorts (<60: 11.25 × 106 vs 60-69: 10.37 × 106 vs ≥70: 7.33 × 106, p=0.0004). In a subset of subjects with available samples, stem cell autograft purity/MRD negativity was higher with KRD (81.1%) than with RVD (59.4%) (p=0.086) (Fig 2 & 3). For both cohorts, MRD negativity was observed in a greater proportion of autografts than pre-collection BMs (Fig 3). For patients who proceeded to transplant, mean time to engraftment after ASCT was comparable (RVD 9.96 vs KRD 10.08 days). Conclusion KRD induces deeper clinical responses and greater stem cell graft purity than RVD without compromising stem cell yield or post-transplant engraftment kinetics, despite decreased viable CD34+ content of autografts and lower stem cell collection totals. [ABSTRACT FROM AUTHOR]