Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition

Topic Information

Dear Colleagues,

This Topic is the second edition of the collection “Myeloma and Leukemia—Challenges and Current Treatment Options”, available at https://www.mdpi.com/topics/LCACTO.

After years of stagnation in the field, in recent years, we have entered into a new era in multiple myeloma and acute leukemia therapy with the discovery of many novel agents. This was due to better knowledge of the biology of the diseases, and of the pathogenesis-related pathways, with the advent of new combinations of drugs and new therapy development, together with an improved understanding of the immune system, resulting in great progress in the development of immune therapies for the treatment of patients, including monoclonal and bispecific antibodies, and CAR-T cell approaches. The numerous ongoing trials evaluating these new opportunities, also considering real-life experiences, are helping to confirm the efficacy and tolerability of these drugs in daily clinical practice. This Special Issue aims to focus on novel agents and their combinations. Focus will be placed on the efficacy of novel drugs and promising combination approaches to further improve outcomes in the treatment of patients with multiple myeloma and acute leukemia. 

We welcome the submission of original research articles, reviews, interesting case reports, and interim data of clinical trials.

Dr. Giovanni Martinelli
Dr. Claudio Cerchione
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
BioMedInformatics biomedinformatics	3.6	7.1	2021	20.8 Days	CHF 1200
Cancers cancers	4.8	9.0	2009	17.5 Days	CHF 2900
Hemato hemato	0.7	1.9	2020	27.2 Days	CHF 1200
Hematology Reports hematolrep	1.9	2.3	2009	26.3 Days	CHF 1600

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Published Papers (6 papers)

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All BioMedInformatics Cancers Hemato Hematology Reports

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20 pages, 628 KB  

Open AccessReview

Acute Myeloid Leukemia in Older Adults: A Comprehensive Narrative Review of Risk Stratification and Treatment Advances

by Ahmed S. Mohamed, Shraboni Dey, Shibhani Rajanna, Marina Basta, Shareif Abdelwahab, Maggie James, Mohammed A. Saafan, Tarneem Deyab and Sameh Elias

Hemato 2026, 7(3), 30; https://doi.org/10.3390/hemato7030030 - 1 Sep 2026

Viewed by 250

Abstract

Acute myeloid leukemia (AML) is predominantly a disease of older adults, with a median age at diagnosis of 68–72 years. Management in this population is complicated by adverse cytogenetic and molecular features, higher rates of secondary disease, and patient-specific factors such as comorbidity [...] Read more.

Acute myeloid leukemia (AML) is predominantly a disease of older adults, with a median age at diagnosis of 68–72 years. Management in this population is complicated by adverse cytogenetic and molecular features, higher rates of secondary disease, and patient-specific factors such as comorbidity and frailty. This narrative review synthesizes the current evidence on risk stratification and treatment of AML in adults aged 60 years and older, with dedicated attention to patients aged 60–75 (“fit” older adults) and those older than 75, including octogenarians. The VIALE-A trial established venetoclax plus azacitidine as standard of care for patients ineligible for intensive chemotherapy (composite complete remission 66.4%; median overall survival 14.7 vs. 9.6 months with azacitidine alone). For fit adults aged 60–75, the choice between intensive chemotherapy and venetoclax-based regimens remains under active investigation, with emerging randomized data suggesting comparable outcomes and a possible advantage for venetoclax-based approaches in adverse-risk disease. Risk stratification has evolved beyond the 2022 European LeukemiaNet (ELN) classification, which was developed in intensively treated cohorts; the 2024 ELN genetic risk classification for less-intensive therapy now provides a framework specific to this population. TP53-mutated AML, including multi-hit disease, remains the dominant unmet need across all treatment modalities. Advances in reduced-intensity conditioning have expanded transplant eligibility into the seventh and eighth decades, and molecularly targeted approaches, including FLT3, IDH1/2, and menin inhibitors, are reshaping frontline and relapsed/refractory therapy. This review covers epidemiology, risk stratification, treatment stratified by age, fitness, and genetic subgroup, the role of transplantation and maintenance therapy, and the limitations of the current evidence base for this heterogeneous population. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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14 pages, 4113 KB  

Open AccessArticle

C-Reactive Protein-to-Albumin Ratio and Its Association with Inflammatory and Renal Parameters in Multiple Myeloma

by Asli Odabasi Giden

Hemato 2026, 7(3), 26; https://doi.org/10.3390/hemato7030026 - 5 Aug 2026

Viewed by 384

Abstract

Background: Multiple myeloma (MM) is a hematological malignancy characterized by systemic inflammation and frequent renal involvement. The C-reactive protein-to-albumin ratio (CAR) has emerged as a potential inflammation-based biomarker; however, its clinical significance in MM remains incompletely understood. Methods: This retrospective single-center study [...] Read more.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by systemic inflammation and frequent renal involvement. The C-reactive protein-to-albumin ratio (CAR) has emerged as a potential inflammation-based biomarker; however, its clinical significance in MM remains incompletely understood. Methods: This retrospective single-center study included 62 patients with MM. Clinical and laboratory data at diagnosis were collected, and CAR was calculated as the ratio of CRP to serum albumin. Patients were stratified into low and high CAR groups based on the median value (0.13). Survival outcomes were assessed using the Kaplan–Meier method. Results: The mean age was 65.9 ± 9.9 years, and 54.8% of patients were male. Higher CAR levels were associated with shorter overall survival (123 vs. 89 months, p = 0.32) and progression-free survival (60 vs. 36 months, p = 0.16), although these differences did not reach statistical significance. An unexpected finding was that the requirement for dialysis was higher in the low-CAR group (21.2% vs. 3.4%, p = 0.04). Other clinical and laboratory parameters were comparable between groups. Conclusions: CAR may reflect systemic inflammatory status in patients with MM; however, its prognostic value for survival remains uncertain in this cohort. The observed findings, particularly regarding renal outcomes, should be interpreted with caution. Larger prospective studies are needed to clarify the clinical utility of CAR in MM. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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15 pages, 1114 KB  

Open AccessSystematic Review

Clinical Outcomes of Daratumumab-Containing Regimens in Multiple Myeloma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Sara O. Elgendy, Mohamed S. Imam, Amal Ali Mohammed Alshehri, Wejdan Zaed Ali Alsufyani, Maha Eid Albogami, Sumayyah Abdullah Saeed Almalki, Maya Nammas M. Alkhaldi, Majdolene Wael Abdulfattah Samarkandi, Demah Turki Yaqoub Alibrahim, Faten Ali Hefdhallah Hakami, Karim Abdelazim, Mostafa Hossam El Din Moawad, Ahmed Hamdy Zabady, Shimaa Sholkamy and Rehab M. Abd-Elkareem

BioMedInformatics 2026, 6(3), 28; https://doi.org/10.3390/biomedinformatics6030028 - 12 May 2026

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Abstract

Background: This study examines the clinical efficacy of daratumumab when combined with other therapeutic agents in patients with multiple myeloma, with a focus on key outcomes including overall response, progression-free survival (PFS), and stringent complete response (sCR). Methods: A systematic literature search was [...] Read more.

Background: This study examines the clinical efficacy of daratumumab when combined with other therapeutic agents in patients with multiple myeloma, with a focus on key outcomes including overall response, progression-free survival (PFS), and stringent complete response (sCR). Methods: A systematic literature search was conducted using PubMed, Web of Science, Scopus, and the Cochrane Library. Statistical analyses were performed with R software (version 4.2.2). Between-study heterogeneity was assessed using the Cochrane Q test and the I² statistic, while potential publication bias was evaluated through Egger’s regression test and visual inspection of funnel plots. Results: The meta-analysis revealed that daratumumab-containing regimens were associated with a 54.4% reduction in the risk of disease progression or death (hazard ratio[HR] 0.4558; 95% confidence-interval [CI]: 0.4031–0.5154). Similar results were observed using a random-effects model (HR 0.4667; 95% CI: 0.3771–0.5776), despite moderate heterogeneity (I² = 66.7%). Moreover, patients treated with daratumumab were approximately 2.4 times more likely to achieve a stringent complete response (odds-ratio[OR] 2.38; 95% CI: 1.80–3.15), with moderate heterogeneity across studies (I² = 58.2%). Conclusions: Incorporating daratumumab into standard therapy for multiple myeloma significantly enhances progression-free survival and the rate of stringent complete response. Despite some heterogeneity, the consistent positive outcomes support its use as an effective treatment option in clinical practice. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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13 pages, 1139 KB  

Open AccessArticle

Comparative Effectiveness of Pomalidomide-Based Regimens in Relapsed/Refractory Multiple Myeloma: A Multicenter Real-World Analysis in China

by Shan Gao, Junling Zhuang, Aijun Liu, Dongmei Wang, Wei Wang, Xin Li, Zhihong Wang, Meiyun Fang, Ming Gong, Zhilin Jia, Sun Wu, Zheng Xu, Genjie Wang and Li Bao

Cancers 2026, 18(7), 1160; https://doi.org/10.3390/cancers18071160 - 3 Apr 2026

Viewed by 1138

Abstract

Background: Although multiple pomalidomide-based combinations are active in relapsed and/or refractory multiple myeloma (RRMM), comparative data to guide regimen selection remain limited. Methods: A total of 230 patients with RRMM from 12 centers in China who received pomalidomide-based regimens were included [...] Read more.

Background: Although multiple pomalidomide-based combinations are active in relapsed and/or refractory multiple myeloma (RRMM), comparative data to guide regimen selection remain limited. Methods: A total of 230 patients with RRMM from 12 centers in China who received pomalidomide-based regimens were included in this retrospective analysis. Overall response rate (ORR) and progression-free survival (PFS) were compared across regimens incorporating bortezomib or ixazomib (V/IPD), carfilzomib (KPD), or daratumumab (DPD), and multivariable analyses were performed to identify prognostic factors. Results: The overall ORR was 73.9%, with rates of 63%, 79%, and 85% in the V/IPD (n = 66), KPD (n = 69), and DPD (n = 95) cohorts, respectively. ORR differed significantly between V/IPD and DPD (p = 0.0165), driven by a higher proportion of ≥VGPR in the DPD group. The median PFS for the entire cohort was 17.4 months (95% CI: 13.7–20.1), compared with 15.4 months (95% CI: 12.8–20.5), 14.2 months (95% CI: 6.9–not estimable), and 19.2 months (95% CI: 15.1–24.9) for V/IPD, KPD, and DPD, respectively, without significant differences. In multivariable analysis, DPD was associated with improved ORR (HR 4.83, p < 0.001) but not with PFS. R-ISS stage III predicted inferior response (HR 0.35, p = 0.04), whereas ≥3 prior lines of therapy correlated with shorter PFS (HR 1.77, p = 0.012). Adverse events were predominantly hematologic, with limited grade 3–4 toxicity and no treatment-related mortality. Conclusions: This multicenter real-world analysis clarifies the relative positioning of commonly used pomalidomide-based regimens in RRMM and underscores the importance of treatment timing and disease stage in optimizing outcomes. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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13 pages, 1577 KB  

Open AccessArticle

Addition of Venetoclax to Azacitidine Did Not Improve Survival in Acute Myeloid Leukemia and Was Not Well Tolerated: Real World Experience

by David Yanni, Nupur Krishnan and Rouslan Kotchetkov

Cancers 2026, 18(5), 841; https://doi.org/10.3390/cancers18050841 - 5 Mar 2026

Viewed by 1304

Abstract

Introduction: Front-line therapy with Azacitidine (AZA) + Venetoclax (Ven) improved overall survival (OS) and remissions in acute myeloid leukemia (AML) patients ineligible for standard induction. Less is known about the outcome of AML treated with AZA + Ven in the “real world”. [...] Read more.

Introduction: Front-line therapy with Azacitidine (AZA) + Venetoclax (Ven) improved overall survival (OS) and remissions in acute myeloid leukemia (AML) patients ineligible for standard induction. Less is known about the outcome of AML treated with AZA + Ven in the “real world”. Methods: We assessed the comparative pattern of administration, tolerability, efficacy and safety of AZA vs. AZA + Ven administered at our cancer centre. We retrospectively reviewed all patients treated with AZA alone or AZA + Ven. Patients who received less than one cycle or proceeded with consolidative stem cell transplant were excluded. Results: A total of 53 patients, median age 77 years, received AZA, and 23 patients, median age 73 years, received AZA + Ven. Among those, 69% and 47.8% were ≥75 years old, respectively. Only 52% received Ven doses above 200 mg. Mean time on therapy was 13.1 months in AZA vs. 5.9 months in AZA + Ven. Treatment delays occurred in 22.6% of AZA and 34.8% of AZA + Ven patients, primarily due to infections and cytopenias. Neutropenia grade 3/4 occurred in 28.3% of AZA vs. 56.5% of AZA + Ven patients. Thrombocytopenia grade 3/4 occurred in 15.1% of AZA and 51.2% of AZA + Ven patients. Anemia grade 3/4 occurred in 5.7% of AZA vs. 30.4% of AZA + Ven patients. Moreover, 69.8% of AZA and 69.5% AZA + Ven patients reached stable disease/partial and complete remission. Median overall survival (OS) was similar: 18 months in AZA vs. 14 months in the AZA + Ven group, p = 0.905. Conclusions: In a community setting, the addition of Venetoclax to AZA did not improve overall survival or disease control, mainly due to low tolerability and higher toxicity. However, these results should be interpreted cautiously due to a significant imbalance in the cytogenetic risk profiles and lower tolerability in the combined group. This suggests the need for a larger study with adjusted analyses. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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19 pages, 2050 KB  

Open AccessArticle

Second Salvage Autologous Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Multiple Myeloma in the Era of Novel Agents: Results of the KMM2301 Study

by Jongheon Jung, Ji Hyun Lee, Sung-Hyun Kim, Jae Hoon Lee, Kwai Han Yoo, Young Rok Do, Ho-jin Shin, Kihyun Kim, Sang Eun Yoon, Dok Hyun Yoon, Hyungwoo Cho, Hye Jin Kang, Ja Min Byun, Jae-Cheol Jo, Seung-Shin Lee, Won Sik Lee, Je-Jung Lee, Sung-Hoon Jung, Myung-Won Lee, Jun Ho Yi, Ju-Hyun Park, Chang-Ki Min and Hyeon-Seok Eomadd Show full author list remove Hide full author list

Cancers 2026, 18(3), 471; https://doi.org/10.3390/cancers18030471 - 30 Jan 2026

Cited by 1 | Viewed by 1350

Abstract

Background: Second salvage autologous stem cell transplantation (SAT) is a therapeutic option for patients with multiple myeloma (MM) who relapse after a first autologous stem cell transplantation (ASCT) in the era of novel agents. However, the clinical context in which SAT provides benefit [...] Read more.

Background: Second salvage autologous stem cell transplantation (SAT) is a therapeutic option for patients with multiple myeloma (MM) who relapse after a first autologous stem cell transplantation (ASCT) in the era of novel agents. However, the clinical context in which SAT provides benefit relative to contemporary salvage regimens remains unclear. Methods: We retrospectively analyzed 51 patients who underwent SAT after novel agent-based induction and first ASCT, and salvage re-induction, and compared outcomes with 113 patients treated with salvage carfilzomib–lenalidomide–dexamethasone (KRd) without SAT. Results: Median interval from first ASCT to relapse was 27 months. In the SAT cohort, median progression-free survival (PFS) and overall survival (OS) from initiation of salvage therapy were 30 and 99 months, respectively. A time to relapse ≥18 months after first ASCT and receipt of SAT as second-line of therapy were associated with significantly longer PFS and OS. In multivariate analysis, administration of SAT at later lines was independently associated with inferior outcomes, while a time to relapse ≥18 months after first ASCT was associated with significantly longer OS. Compared with the KRd-only cohort, SAT was associated with longer OS, whereas PFS was numerically longer without statistical significance. Among patients who had received both a proteasome inhibitor and an immunomodulatory drug as salvage induction, SAT was associated with longer PFS and OS. Conclusions: SAT may provide clinical benefit in selected patients with MM, particularly those with a durable response to first ASCT and those undergoing SAT at an earlier line of relapse in the novel agent era. Full article

(This article belongs to the Topic Myeloma and Leukemia—Challenges and Current Treatment Options: 2nd Edition)

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