Antimicrobial stewardship programs play a critical role in optimizing the use of antimicrobials against pathogens in the era of growing multi-drug resistance. However, implementation of antimicrobial stewardship programs among the hematopoietic stem cell transplant and oncology populations has posed challenges due to multiple risk factors in the host populations and the infections that affect them. The consideration of underlying immunosuppression and a higher risk for poor outcomes have shaped therapeutic decisions for these patients. In this multidisciplinary perspective piece, we provide a summary of the current landscape of antimicrobial stewardship, unique challenges, and opportunities for unmet needs in these patient populations.

Background/Objectives: Teclistamab is a bispecific antibody targeting BCMA and CD3, approved for relapsed/refractory multiple myeloma. It is administered continuously until progression or intolerance; however, prolonged use may increase infections and treatment burden. This study compares continuous versus fixed-duration teclistamab to determine whether treatment discontinuation after response is feasible without compromising outcomes. Methods: A multicenter retrospective study was conducted on adults with relapsed/refractory multiple myeloma treated with teclistamab between August 2022 and May 2024. Patients received step-up dosing followed by weekly administration. Those who achieved ≥VGPR and discontinued therapy due to deep response, toxicity, or preference were assigned to the fixed-duration group. Outcomes included response rates, progression-free survival (PFS), overall survival (OS), and adverse events. Results: Eighty-eight patients were included (continuous: n = 72; fixed: n = 16). The fixed group had higher complete response rates (69% vs. 44%) and shorter median time to best response (1 vs. 2 months). Median PFS was 16 months for continuous dosing versus 13 months for fixed-duration. Twelve-month PFS was similar (65% vs. 66%). Twelve-month OS was 83% vs. 81% in the continuous and fixed groups, respectively. Cytokine release syndrome and neurotoxicity rates were similar. Infections were more frequent and severe in the fixed cohort (75% any grade; 69% grade ≥ 3). Conclusions: Fixed-duration teclistamab after deep response appears feasible in appropriately selected patients, with comparable early survival outcomes to continuous treatment. Prospective studies are needed to define selection criteria, immune recovery markers, and optimal discontinuation timing.

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells and a rapidly evolving treatment landscape. Bispecific antibodies targeting B-cell maturation antigens (BCMA) have emerged as promising therapeutic options for relapsed and/or refractory multiple myeloma (RRMM). Methods: This retrospective study evaluated the efficacy and safety of teclistamab, a BCMA-directed bispecific antibody, in patients with RRMM with renal impairment (RI) at baseline compared to those without. Conducted across seven academic centers, the study included 195 patients with RRMM, of whom 34 had baseline RI. Results: Performance status, previous lines of treatment, and prior BCMA exposure were identified as significant predictors of progression-free survival. Notably, patients with RI demonstrated overall response rates and toxicity profiles comparable to those without RI, although they required more packed red blood cell transfusions. No statistically significant differences were observed in adverse events, including cytokine release syndrome and infections. Conclusions: Overall, the findings support the efficacy and safety of teclistamab in patients with RRMM and RI, highlighting the need for prospective clinical trials to optimize the treatment strategies for this population.

Background: High-risk cytogenetic multiple myeloma (HRMM) confers inferior outcomes despite significant therapeutic advances. Real-world data characterizing contemporary treatment patterns across lines of therapy in this population are limited. Methods: We conducted a multicenter retrospective study of 205 patients with HRMM diagnosed between January 2009 and January 2024. High-risk cytogenetics were defined according to the International Myeloma Working Group (IMWG) and Revised International Staging System (R-ISS) criteria as the presence of del(17p), t(4;14), t(14;16), t(14;20), and/or gain/amplification of 1q21. Treatment regimens were categorized by the number of agents (doublet, triplet, quadruplet), mechanism of action (proteasome inhibitor [PI]-based, immunomodulatory drug [IMiD]-based, and anti-CD38 monoclonal antibody-based), and specific regimen composition. Treatment patterns were analyzed across three treatment eras and stratified by age (<70 vs. ≥70 years). Results: The cohort included 205 patients (median age, 62 years [interquartile range [IQR], 54–68 years]; 78.5% aged <70 years). Double-hit and triple-hit cytogenetics were present in 60.0% and 7.3% of patients, respectively. For first-line induction, triplet therapy predominated (81.0%, n = 166), followed by quadruplet (8.8%, n = 18), doublet (5.9%, n = 12), and multi-agent chemotherapy (2.9%, n = 6). By mechanism of action, PI + IMiD combinations were the most common (63.4%, n = 130), followed by PI-based (19.0%, n = 39), anti-CD38-based (10.2%, n = 21), and IMiD-based (2.9%, n = 6) regimens. Era-stratified analysis revealed a significant increase in quadruplet utilization from 3.2% in Era 1 (2009–2015) to 20.3% in Era 3 (2020–2024), with anti-CD38-containing frontline regimens administered to 26.6% of patients in the contemporary era (p < 0.001). Second-line induction was required in 50 patients (24.4%), with anti-CD38-based triplets comprising the most common approach (30.0%). Autologous stem cell transplantation (ASCT) was performed in 75.1% of patients overall, with significantly higher utilization in those aged <70 years (83.9% vs. 43.2%). Maintenance therapy was administered to 71.7% of patients (n = 147), with IMiD-based regimens predominating (53.1%), followed by PI + IMiD combinations (27.9%) and anti-CD38-containing regimens (10.2%). Despite intensive therapy, 69.4% of patients on maintenance experienced disease relapse, with higher rates observed in younger patients (74.8% vs. 41.7%). Conclusions: In this real-world HRMM cohort, the PI + IMiD triplet regimen remained the predominant induction approach, with a significant shift toward quadruplet and anti-CD38-containing regimens in the contemporary era. However, substantial relapse rates during maintenance underscore the continued unmet need in HRMM and support the early integration of novel therapeutic strategies, including quadruplet induction and BCMA-directed agents, in this population.