Effectiveness, Safety, and Cost Implications of Outpatient Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma.

BACKGROUND AND OBJECTIVE: Autologous hematopoietic stem cell transplant (aHCT) has become standard care for patients with multiple myeloma (MM). Outpatient aHCT with high-dose melphalan conditioning has reduced costs and length of hospital stay. This study aimed to highlight the effectiveness, safety, and cost implications of outpatient vs inpatient aHCT at a tertiary academic medical center, as well as the utility of growth factor use in these patients. PATIENTS AND METHODS: Using an institutional HCT database, a total of 100 patients undergoing aHCT for MM were identified; 50 patients who underwent aHCT in the outpatient setting (chemotherapy and stem cell infusion followed by inpatient admission if needed) were compared with 50 patients in the inpatient setting (chemotherapy and stem cell infusion followed by discharge to outpatient setting). Patients were excluded if the melphalan dose was less than 200 mg/m2. Outcomes assessed through retrospective chart review included time to engraftment, incidence of infection, febrile neutropenia, growth factor use, and total length of inpatient stay through day +100. RESULTS: Time to neutrophil and platelet engraftment was shorter in the outpatient group than in the inpatient group (14 vs 16 days and 19 vs 21 days, respectively; P < 0.001). Median length of hospital stay was also shorter in the outpatient group (8.5 vs 15.5 days, respectively; P < 0.001). Ninety percent of the outpatient group required admission for neutropenic fever, and 60% of these patients received growth factor support starting at a median of 9 days after stem cell infusion, for a median duration of 4 days. Compared to 16 patients who did not receive growth factor support, these patients had a significantly shorter time to neutrophil recovery (13 days with vs 15 days without growth factor, P = 0.02) and no difference in the total length of hospital stay (8 days with vs 10 days without growth factor, P = 0.43). CONCLUSION: For adult patients with MM undergoing aHCT, the outpatient setting is safe and reduces the total length of hospital stay and thus overall transplant costs. Growth factor support for patients with febrile neutropenia may not reduce length of stay for subsequent hospitalizations.

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma.

BACKGROUND: In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody (triple-class exposed). PATIENTS AND METHODS: A dataset of US patients refractory to an anti-CD38 monoclonal antibody (MAMMOTH) was used to identify patients who would meet eligibility for CARTITUDE-1 and received subsequent non-CAR-T therapy. The intent-to-treat (ITT) population in CARTITUDE-1 included patients who underwent apheresis (N = 113); the modified ITT (mITT) population was the subset who received cilta-cel (n = 97). Corresponding populations were identified from the MAMMOTH dataset: ITT population (n = 190) and mITT population of patients without progression/death within 47 days (median apheresis-to-cilta-cel infusion time) from onset of therapy (n = 122). Using 1:1 nearest neighbor propensity score matching to control for selected baseline covariates, 95 and 69 patients in CARTITUDE-1 ITT and mITT populations, respectively, were matched to MAMMOTH patients. RESULTS: In ITT cohorts of CARTITUDE-1 vs. MAMMOTH, improved overall response rate (ORR; 84% vs. 28% [P < .001]) and longer progression-free survival (PFS; hazard ratio [HR], 0.11 [95% confidence interval (CI), 0.05-0.22]) and overall survival (OS; HR, 0.20 [95% CI, 0.10-0.39]) were observed. Similar results were seen in mITT cohorts of CARTITUDE-1 vs. MAMMOTH (ORR: 96% vs. 30% [P < .001]; PFS: HR, 0.02 [95% CI, 0.01-0.14]; OS: HR, 0.05 [95% CI, 0.01-0.22]) and with alternative matching methods. CONCLUSION: Cilta-cel yielded significantly improved outcomes versus real-world therapies in triple-class exposed patients with relapsed/refractory MM.

Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy.

The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T0) was 50.1 months. The median overall survival (OS) from T0 for the entire cohort was 8.6 [95% C.I. 7.5-9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for "penta-refractory" patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T0 in 249 (90%) patients. Overall response rate to first regimen after T0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.

IgM Myeloma with Plasma Cell Leukemia: Case Report and Literature Review.

IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation. Plasma cell leukemia (PCL) is a rare and aggressive variant of MM characterized by the presence of circulating plasma cells. We present a case report of a patient who presented with IgM MM in primary PCL phase with high-risk cytogenetics. To our knowledge, this is the first reported case of IgM MM with primarily leukemic presentation in the era of novel drugs. We demonstrate that it is important to distinguish IgM MM from WM and review the data from clinical trials that was used to devise a treatment strategy for this high-risk patient. This case adds to the understanding of the diagnosis and management of IgM MM in leukemic phase.