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Current Oncology
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U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection
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U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 4054

Special Issue Editor

Dr. Al-Ola A. Abdallah

E-Mail Website
Guest Editor
Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66205, USA
Interests: multiple myeloma; immuno-cellular therapies in multiple myeloma; drug-resistant multiple myeloma; drug-development in heavily treated relapse myeloma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue highlights the collaborative innovation emerging from our integrated myeloma research programs, dedicated to transforming outcomes through next-generation immunotherapy, cellular therapy, and precision-based translational science. Our projects span the full spectrum of immune-based strategies—including CAR-T cells, T-cell engagers (TCEs), bispecific and trispecific platforms, and novel targets such as BCMA, GPRC5D, and emerging noncanonical antigens. In partnership with national and international collaborators across academic centers, cooperative groups, and the U.S. Myeloma Innovations Research Collaborative (USMIRC), our work aims to define mechanisms of resistance, optimize sequencing, and expand access to cutting-edge therapies for patients with multiple myeloma and other plasma cell disorders. Together, these initiatives create a multidisciplinary ecosystem accelerating discovery, clinical translation, and real-world impact.

Dr. Al-Ola A. Abdallah
Guest Editor

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As stated above, the central purpose of this Special Issue is to present research from U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection. Given this purpose, the Guest Editors’ contribution to this Special Issue may be greater than standard Special Issues published by MDPI. Further details on MDPI's Special Issue guidelines can be found here: https://www.mdpi.com/special_issues_guidelines. The Editorial Office and Editor-in-Chief of Current Oncology has approved this and MDPI’s standard manuscript editorial processing procedure (https://www.mdpi.com/editorial_process) will be applied to all submissions. As per our standard procedure, Guest Editors are excluded from participating in the editorial process for their submission and/or for submissions from persons with whom a potential conflict of interest may exist. More details on MDPI’s Conflict of Interest policy for reviewers and editors can be found here: https://www.mdpi.com/ethics#_bookmark22.

Keywords

  • multiple myeloma
  • immunotherapy
  • cellular therapy
  • CAR-T
  • T-cell engagers
  • TCE
  • multispecifics
  • BCMA
  • GPRC5D
  • plasmacytoma

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Published Papers (4 papers)

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18 pages, 400 KB  
Article
High-Risk Cytogenetic Multiple Myeloma Remains a Therapeutic Challenge: A 15-Year Real-World Analysis
by Carmel Awadallah, Anas Zayad, Shebli Atrash, Anita Mazloom, Omar Alkharabsheh, Prerna Mewawalla, Mansi R. Shah, Forat Lutfi, Zahra Mahmoudjafari, Muhammad Umair Mushtaq, Jeries Kort, Alma Habib and Al-Ola Abdallah
Curr. Oncol. 2026, 33(5), 249; https://doi.org/10.3390/curroncol33050249 - 27 Apr 2026
Viewed by 116
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection)
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17 pages, 717 KB  
Article
Outcomes of Double-Hit and Single High-Risk Cytogenetic Newly Diagnosed Myeloma in Transplant-Eligible Patients
by Raeef Rahman, Anas Zayad, Carmel Awadallah, Beining Wang, Jianzheng Wu, Aroog Khaliq, Prerna Mewawalla, Shebli Atrash, Dinesh Pal Mudaranthakam, Joseph McGuirk, Zahra Mahmoudjafari, Muhammad Umair Mushtaq, Al-Ola Abdallah, Nausheen Ahmed, Jordan Snyder, Anita Mazloom, Omar Alkharabsheh and Mansi R. Shah
Curr. Oncol. 2026, 33(5), 246; https://doi.org/10.3390/curroncol33050246 - 26 Apr 2026
Viewed by 256
Abstract
Introduction: High-risk multiple myeloma (HRMM) is primarily defined by adverse cytogenetic abnormalities that are associated with inferior outcomes despite contemporary treatment with novel induction agents and autologous stem cell transplantation (ASCT). While the accumulation of high-risk lesions has been proposed to further stratify [...] Read more.
Introduction: High-risk multiple myeloma (HRMM) is primarily defined by adverse cytogenetic abnormalities that are associated with inferior outcomes despite contemporary treatment with novel induction agents and autologous stem cell transplantation (ASCT). While the accumulation of high-risk lesions has been proposed to further stratify prognosis, the relative impact of single-hit versus double-hit HRMM on post-transplant outcomes in real-world clinical practice remains incompletely characterized. Methods: We conducted a multicenter retrospective cohort study of transplant-eligible adults with HRMM undergoing upfront ASCT between 2009 and 2024 at three U.S. academic centers. Patients were categorized as single-hit HRMM or double-hit HRMM based on the number of high-risk cytogenetic abnormalities at diagnosis. Response rates, progression-free survival (PFS), and overall survival (OS) were compared between groups using standard statistical methods. Results: A total of 154 patients were included, of whom 63 had SH-HRMM, and 91 had DH-HRMM. Following induction therapy, overall response rates (ORR) were high and comparable between groups. After ASCT, ORR was significantly higher in SH-HRMM compared with DH-HRMM (97% vs. 82%, p = 0.006), although depth of response did not differ significantly. With a median follow-up of 150 months, median OS was 103 months in SH-HRMM and 94 months in DH-HRMM (p = 0.40). Median PFS was 36 months and 31 months, respectively (p = 0.20). Restricted mean survival time analyses similarly demonstrated no significant differences in OS or PFS between groups. Although ORR differed, depth of response and long-term survival did not. Conclusions: In this real-world cohort of transplant-treated HRMM, single-hit disease was associated with a higher likelihood of achieving post-ASCT response; however, no significant differences in long-term survival outcomes were observed between single-hit and double-hit HRMM. These findings suggest that cytogenetic hit burden alone may be insufficient to predict post-transplant survival, highlighting the need for refined risk stratification incorporating additional biological and response-based markers. Full article
(This article belongs to the Special Issue U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection)
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14 pages, 1130 KB  
Article
Maintenance Strategies in High-Risk Myeloma: A Multicenter Comparison of Bortezomib–Lenalidomide Versus Lenalidomide Alone: A USMIRC Multicenter Analysis
by Sruthi P. Ramanan, Oyepeju F. Abioye, Shebli Atrash, Jianzheng Wu, Dinesh Pal Mudaranthakam, Anita Mazloom, Omar Alkharabsheh, Mansi R. Shah, Zahra Mahmoudjafari, Jordan Snyder, Muhammad Umair Mushtaq, Forat Lutfi, Jeries Kort, Al-Ola Abdallah and Prerna Mewawalla
Curr. Oncol. 2026, 33(3), 164; https://doi.org/10.3390/curroncol33030164 - 13 Mar 2026
Viewed by 1644
Abstract
Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ [...] Read more.
Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ doublet maintenance with bortezomib plus lenalidomide (VR). We evaluated outcomes with VR versus lenalidomide alone (R) in HRMM. Methods: We conducted a multicenter retrospective study through the US Myeloma Innovations Research Collaborative (USMIRC), including adults with HRMM who received R or VR maintenance following ASCT between January 2009 and January 2024. HRMM was defined by del(17p), t(4;14), t(14;16), or t(14;20), with or without 1q gain. PFS and OS were estimated using Kaplan–Meier methods. Median follow-up was 91 months. Baseline characteristics, induction regimens, and post-transplant response depth were well balanced between the groups. Median PFS was 51 months (95% CI, 20–NR) with VR and 36 months (95% CI, 31–56) with R (p > 0.05). Median OS was 103 months (95% CI, 90–NR) and 110 months (95% CI, 94–NR), respectively (p > 0.05). VR was associated with numerically longer PFS, although the difference was not statistically significant. No treatment-related mortality occurred within 100 days post-ASCT. Conclusions: In this multicenter real-world analysis of HRMM, VR maintenance did not result in statistically significant improvements in PFS or OS compared with lenalidomide alone. These findings underscore the need for prospective, risk-adapted trials incorporating novel maintenance strategies, including CD38- and BCMA-directed therapies, in high-risk disease. Full article
(This article belongs to the Special Issue U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection)
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10 pages, 1186 KB  
Article
BCMA-Directed CAR T-Cell Therapy in Patients with Relapsed/Refractory Multiple Myeloma and Renal Impairment
by Alma Habib, Nausheen Ahmed, Abdullah Mohammad Khan, Darryl Chang, Barry Paul, Hira Shaikh, Christopher Strouse, Emily Struble, Andrew Vegel, Zahra Mahmoudjafari, Muhammad Umair Mushtaq, Joseph P. McGuirk, Al-Ola Abdallah, Shebli Atrash and Reed Friend
Curr. Oncol. 2026, 33(2), 80; https://doi.org/10.3390/curroncol33020080 - 30 Jan 2026
Cited by 2 | Viewed by 1547
Abstract
The pivotal clinical trials, CARTITUDE-1 and KarMMa-3, showed promising response rates in relapsed and refractory multiple myeloma (RRMM) with use of BCMA-directed CAR T-cell therapy; however, a major challenge is determining suitability in patients who do not meet trial inclusion criteria due to [...] Read more.
The pivotal clinical trials, CARTITUDE-1 and KarMMa-3, showed promising response rates in relapsed and refractory multiple myeloma (RRMM) with use of BCMA-directed CAR T-cell therapy; however, a major challenge is determining suitability in patients who do not meet trial inclusion criteria due to suboptimal organ function. In this multicenter retrospective study, we evaluated the safety and efficacy of BCMA CAR-T therapy in patients with RRMM and renal impairment (RI), defined as creatinine clearance (CrCL) of less than 45 mL/min. We evaluated 223 patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) between May 2021 and April 2024. Outcomes were compared between baseline RI (11.2%) and normal renal function (nRF) cohorts. Response rates were similar at 1 month (p = 0.09), 3 months (p > 0.9), and 6 months (p = 0.8). Progression-free survival (PFS) was 21.9 months in the RI group compared to 15 months in the nRF group (p = 0.32), while overall survival (OS) was 27.9 months for patients with nRF versus not reached for patients with RI (p = 0.87). Patients with RI had higher rates of immune effector cell-associated neurotoxicity syndrome (ICANS) (60% vs. 19%, p = 0.04) and infections (44% vs. 20%, p = 0.008). We found that BCMA CAR-T demonstrated comparable efficacy in RRMM patients with baseline RI, although these patients exhibited increased rates of neurotoxicity and infections. Full article
(This article belongs to the Special Issue U.S. Myeloma Innovations Research Collaborative (USMIRC) Collection)
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