A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse.

INTRODUCTION: Treatment of patients with multiple myeloma (MM) in first relapse remains a challenge. This phase II study combined elotuzumab (Elo) with carfilzomib, lenalidomide, and dexamethasone (KRd) for treatment of MM in first relapse with the aim of improving efficacy. METHODS: Enrolled patients received Elo-KRd induction for 4 cycles, and Elo-lenalidomide maintenance until progression. The primary endpoint was VGPR or better (≥VGPR) postinduction. Secondary endpoints were MRD by flow cytometry, OS, PFS, and safety. Correlatives included characterization of the impact of Elo-KRd on NK and T cell subsets via flow cytometry. Target accrual of 40 patients was not met due to COVID-19 pandemic. RESULTS: Of 15 patients enrolled, 10 (67%) had high-risk features (del17p, t[4;14], t[14;16], 1q gain/amplification, plasma cell leukemia, extramedullary MM, or functional high risk), 12 (80%) were lenalidomide-refractory, and 5 (33.3%) bortezomib-refractory. Postinduction ≥VGPR was 7/15 (46.7%) and MRD-negative (10-5) rate 20%. Overall response during study was 80%, including ≥VGPR as best response of 53.3%. At median follow-up of 28.2 (range, 3.8 to 44.2) months, the median PFS was 11.5 months (95% CI 1.9, 18), and median OS not reached (95% CI 10.1, NA). No new safety concerns were reported. Elo-KRd treatment did not augment NK cell distribution or activity in blood or bone marrow. Effector CD4+ and CD8+ T cells significantly decreased postinduction, with concomitant acquisition of T central memory phenotype, particularly at a high rate in ≥VGPR group. CONCLUSION: A short course of Elo-KRd induction followed by Elo-lenalidomide maintenance demonstrated activity in predominantly lenalidomide-refractory and / or high-risk MM. The results with this well-tolerated combination are comparable to other contemporary approved triplet combinations.

Retrospective Review of Outcomes of Multiple Myeloma (MM) Patients With COVID-19 Infection (Two-Center Study).

INTRODUCTION: COVID-19 has profound effects on patients with multiple myeloma (MM) mainly due to underlying immune dysfunction and associated therapies leading to increased susceptibility to infections. The overall risk of morbidity and mortality (M&M) in MM patients due to COVID-19 infection is unclear with various studies suggesting case fatality rate of 22% to 29%. Additionally, most of these studies did not stratify patients by their molecular risk profile. METHODS: Here, we aim to investigate the effects of COVID-19 infection with associated risk factors in MM patients and the effectiveness of newly implemented screening and treatment protocols on outcomes. After obtaining institutional review board approvals from each participating institution, we collected data from MM patients diagnosed with SARS-CoV-2 infection from March 1, 2020, to October 30, 2020, at 2 myeloma centers (Levine Cancer Institute & University of Kansas medical center). RESULTS: We identified a total of 162 MM patients who had COVID-19 infection. The majority of patients were males (57%) with a median age of 64 years. Most patients had an associated comorbid condition. Their myeloma disease status and prior autologous stem cell transplant at the time of infection had no impact on hospitalization or mortality. In univariate analysis, chronic kidney disease, hepatic dysfunction, diabetes, and hypertension were associated with an increased risk of hospitalization. In multivariate analysis regarding survival, increased age and lymphopenia were associated with increased COVID-19-related mortality. CONCLUSION: Our study supports the use of infection mitigation measures in all MM patients, and adjustment of treatment pathways in MM patients diagnosed with COVID-19.

Neutralizing antibody responses against SARS-CoV-2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination.

Many patients with plasma cell disorder (PCD) on active treatment with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require hospitalization, with an increased mortality rate over healthy adults. The FDA approved two mRNA vaccines against SARS-CoV-2: BNT162b2 and mRNA-1273. To assess the efficacy of vaccination in patients with PCD, retrospectively, we identified all patients on active treatment. A total of 149 patients were included. Neutralizing antibodies (NAbs) levels against SARS-CoV-2 adequate, intermediate, and no response were observed in 42%, 32%, and 26%, respectively. Low NAbs were seen in patients on daratumumab combinations or anti-BCMA therapy, low lymphocytes, and low IgG levels. Twenty-three (15%) patients have SARS CoV-2, while 8% required hospitalization, majority of these patients had intermediate or no response based on NAbs levels. Therefore, checking NAbs may be clinically helpful in identifying patients' responses. Further prospective studies should ascertain the value of a third vaccine dose in this population.