Myeloma and Leukemia-Challenges and Current Treatment Options

Topic Information

Dear Colleagues,

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. 

Dr. Giovanni Martinelli
Dr. Claudio Cerchione
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
BioMedInformatics biomedinformatics	-	-	2021	21 Days	CHF 1000	Submit
Cancers cancers	5.2	7.4	2009	17.9 Days	CHF 2900	Submit
Current Oncology curroncol	2.6	2.6	1994	18 Days	CHF 2200	Submit
Hemato hemato	-	-	2020	28.1 Days	CHF 1000	Submit
Hematology Reports hematolrep	0.9	1.1	2009	38.9 Days	CHF 1600	Submit

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Published Papers (8 papers)

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All BioMedInformatics Cancers Current Oncology Hemato Hematology Reports

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11 pages, 821 KiB  

Open AccessArticle

Late Relapse after Allogeneic Stem Cell Transplantation in Patients Treated for Acute Myeloid Leukemia: Relapse Incidence, Characteristics, Role of Conditioning Regimen, and Outcome

by Chloé Antier, Maxime Jullien, Benoît Tessoulin, Marion Loirat, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Patrice Chevallier and Thierry Guillaume

Cancers 2024, 16(7), 1419; https://doi.org/10.3390/cancers16071419 - 05 Apr 2024

Viewed by 509

Abstract

Late relapse, beyond 2 years following alloHSCT for AML, is rare. Among the 376 patients allografted for AML in our center between 1990 and 2016, 142 (38%) relapsed. The majority (68%) of relapses occurred during the first year following transplantation. Beyond 2 years [...] Read more.

Late relapse, beyond 2 years following alloHSCT for AML, is rare. Among the 376 patients allografted for AML in our center between 1990 and 2016, 142 (38%) relapsed. The majority (68%) of relapses occurred during the first year following transplantation. Beyond 2 years after alloHSCT, relapse was observed in 26 patients, representing 6.9% of the whole transplanted cohort and 18.3% of the relapsing patients. Cytogenetics at relapse was available in 21 patients and remained for 15 of them concordant to that at diagnosis. The majority (85.7%) of the patients were in CR prior to transplant. Thirteen patients had grade 1–2 acute GvHD, while 13 other patients had grade 3–4 acute GvHD. None of these patients subsequently developed chronic GvHD. In multivariate analyses, a predictive factor of the absence of relapse 2 years after transplantation was the development of extensive chronic GVHD. Salvage therapy achieved new CR in 77% of these patients. We conclude that late relapse can affect a significant minority of patients allografted for AML, and the intensity of the conditioning regimen does not seem to have an impact on these relapses. Moreover, we were able to show that those patients can receive effective salvage therapy. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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19 pages, 527 KiB  

Open AccessGuidelines

Cell Therapy Transplant Canada (CTTC) Consensus-Based Guideline 2024 for Management and Treatment of Chronic Graft-Versus-Host Disease and Future Directions for Development

by Dennis Dong Hwan Kim, Gizelle Popradi, Kylie Lepic, Kristjan Paulson, David Allan, Ram Vasudevan Nampoothiri, Sylvie Lachance, Uday Deotare, Jennifer White, Mohamed Elemary, Kareem Jamani, Christina Fraga, Christopher Lemieux, Igor Novitzky-Basso, Arjun Datt Law, Rajat Kumar, Irwin Walker and Kirk R. Schultz

Curr. Oncol. 2024, 31(3), 1426-1444; https://doi.org/10.3390/curroncol31030108 - 08 Mar 2024

Viewed by 1263

Abstract

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare [...] Read more.

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD. This document will provide comprehensive and practical guidance that can be applied across Canada by healthcare professionals caring for patients with cGvHD. Hopefully, this guideline, based on input from GvHD treaters across the country, will aid in standardizing cGvHD care and facilitate access to much-needed novel therapies. This consensus paper aims to discuss the optimal approach to the initial assessment of cGvHD, review the severity scoring and global grading system, discuss systemic and topical treatments, as well as supportive therapies, and propose a therapeutic algorithm for frontline and subsequent lines of cGvHD treatment in adults and pediatric patients. Finally, we will make suggestions about the future direction of cGvHD treatment development such as (1) a mode-of-action-based cGvHD drug selection, according to the pathogenesis of cGvHD, (2) a combination strategy with the introduction of newer targeted drugs, (3) a steroid-free regimen, particularly for front line therapy for cGvHD treatment, and (4) a pre-emptive approach which can prevent the progression of cGvHD in high-risk patients destined to develop severe and highly morbid forms of cGvHD. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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12 pages, 2082 KiB  

Open AccessArticle

Inhibition of Enhancer of Zeste Homolog 2 Induces Blast Differentiation, Impairs Engraftment and Prolongs Survival in Murine Models of Acute Myeloid Leukemia

by Sydney Fobare, Ola A. Elgamal, Mark Wunderlich, Emily Stahl, Abeera Mehmood, Casie Furby, James R. Lerma, Thomas M. Sesterhenn, Jianmin Pan, Jayesh Rai, Megan E. Johnstone, Amina Abdul-Aziz, Mariah L. Johnson, Shesh N. Rai, John C. Byrd and Erin Hertlein

Cancers 2024, 16(3), 569; https://doi.org/10.3390/cancers16030569 - 29 Jan 2024

Viewed by 872

Abstract

Background: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to [...] Read more.

Background: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to a specific mutation that is only present in a subset of AML patients. In the current study, we show that targeting the epigenetic modifier enhancer of zeste homolog 2 (EZH2) can induce the differentiation of immature blast cells into a more mature myeloid phenotype and promote survival in AML murine models. Methods: The EZH2 inhibitor EPZ011989 (EPZ) was studied in AML cell lines, primary in AML cells and normal CD34+ stem cells. A pharmacodynamic assessment of H3K27me3; studies of differentiation, cell growth, and colony formation; and in vivo therapeutic studies including the influence on primary AML cell engraftment were also conducted. Results: EPZ inhibited H3K27me3 in AML cell lines and primary AML samples in vitro. EZH2 inhibition reduced colony formation in multiple AML cell lines and primary AML samples, while exhibiting no effect on colony formation in normal CD34+ stem cells. In AML cells, EPZ promoted phenotypic evidence of differentiation. Finally, the pretreatment of primary AML cells with EPZ significantly delayed engraftment and prolonged the overall survival when engrafted into immunodeficient mice. Conclusions: Despite evidence that EZH2 silencing in MDS/MPN can promote AML pathogenesis, our data demonstrate that the therapeutic inhibition of EZH2 in established AML has the potential to improve survival. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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13 pages, 1057 KiB  

Open AccessEditor’s ChoiceArticle

Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study

by Nicola Stefano Fracchiolla, Mariarita Sciumè, Cristina Papayannidis, Antonella Vitale, Sabina Chiaretti, Mario Annunziata, Fabio Giglio, Prassede Salutari, Fabio Forghieri, Davide Lazzarotto, Monia Lunghi, Annalisa Imovilli, Barbara Scappini, Massimiliano Bonifacio, Michelina Dargenio, Carmela Gurrieri, Elisabetta Todisco, Marzia Defina, Maria Ilaria Del Principe, Patrizia Zappasodi, Marco Cerrano, Lidia Santoro, Elena Tagliaferri, Enrico Barozzi, Pasquale De Roberto, Marta Canzi, Elisa Buzzatti, Chiara Sartor, Francesco Passamonti, Robin Foà and Antonio Curtiadd Show full author list remove Hide full author list

Cancers 2023, 15(18), 4623; https://doi.org/10.3390/cancers15184623 - 19 Sep 2023

Cited by 1 | Viewed by 1460

Abstract

Background: Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy. Methods: We describe 71 R/R B-ALL patients treated for different relapses with Blina [...] Read more.

Background: Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy. Methods: We describe 71 R/R B-ALL patients treated for different relapses with Blina and InO. Blina was the first treatment in 57 patients and InO in 14. Twenty-seven patients had a previous allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: In the Blina/InO group, after Blina, 36 patients (63%) achieved a complete remission (CR), with 42% of negative minimal residual disease (MRD−); after InO, a CR was achieved in 47 patients (82%, 34 MRD−). In the InO/Blina group, after InO, 13 cases (93%) reached a CR (6 MRD−); after Blina, a CR was re-achieved in 6 cases (43%, 3 MRD−). Twenty-six patients proceeded to allo-HSCT. In the Blina/InO group, the median overall survival (OS) was 19 months; the disease-free survival (DFS) after Blina was 7.4 months (11.6 vs. 2.7 months in MRD− vs. MRD+, p = 0.03) and after InO, 5.4 months. In the InO/Blina group, the median OS was 9.4 months; the median DFS after InO was 5.1 months and 1.5 months after Blina (8.7 vs. 2.5 months in MRD− vs. MRD+, p = 0.02). With a median follow-up of 16.5 months from the start of immunotherapy, 24 patients (34%) are alive and 16 (22%) are alive in CR. Conclusion: In our series of R/R B-ALL, Blina and InO treatment demonstrate efficacy for subsequent relapses in terms of MRD response, OS and DFS, and as a bridge to allo-HSCT. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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21 pages, 2425 KiB  

Open AccessArticle

Clinical Outcomes in a Large Canadian Centralized CLL Clinic Based on Treatment and Molecular Factors over a Decade

by Jiayu Yang, Lin Yang, Bryan Tordon, Oliver Bucher, Zoann Nugent, Ivan Landego, Nicole Bourrier, Kelsey Uminski, Kevin Brown, Mandy Squires, Aaron J. Marshall, Sachin Katyal, Salah Mahmud, Kathleen Decker, Marc Geirnaert, David E. Dawe, Spencer B. Gibson, James B. Johnston and Versha Banerji

Curr. Oncol. 2023, 30(7), 6411-6431; https://doi.org/10.3390/curroncol30070472 - 05 Jul 2023

Cited by 1 | Viewed by 1444

Abstract

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical [...] Read more.

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton’s tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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21 pages, 1603 KiB  

Open AccessReview

Paradigm Shift in the Management of Acute Myeloid Leukemia—Approved Options in 2023

by Naveen Premnath and Yazan F. Madanat

Cancers 2023, 15(11), 3002; https://doi.org/10.3390/cancers15113002 - 31 May 2023

Cited by 2 | Viewed by 3327

Abstract

The word Leukemia was coined nearly 200 years ago by Rudolf Virchow. Once a death sentence, Acute Myeloid Leukemia (AML) is now a treatable condition. The introduction of “7 + 3” chemotherapy, originally reported from the Roswell Park Memorial institute in Buffalo, New [...] Read more.

The word Leukemia was coined nearly 200 years ago by Rudolf Virchow. Once a death sentence, Acute Myeloid Leukemia (AML) is now a treatable condition. The introduction of “7 + 3” chemotherapy, originally reported from the Roswell Park Memorial institute in Buffalo, New York, in 1973, changed the treatment paradigm for AML. About twenty-seven years later, FDA approved the first targeted agent, gemtuzumab, to be added to this backbone. During the last seven years, we have had ten new drugs approved for the management of patients with AML. Work by many dedicated scientists led to AML achieving the elite status of being the first cancer to have the whole genome sequenced using next-generation sequencing. In the year 2022, we witnessed the introduction of new classification systems for AML by the international consensus classification and the world health organization, both emphasizing molecular classification of the disease. In addition, the introduction of agents such as venetoclax and targeted therapies have changed the treatment paradigm in older patients ineligible for intensive therapy. In this review, we cover the rationale and evidence behind these regimens and provide insights into the newer agents. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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16 pages, 1443 KiB  

Open AccessReview

Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment

by Shinichiro Takahashi

Hematol. Rep. 2023, 15(2), 331-346; https://doi.org/10.3390/hematolrep15020035 - 24 May 2023

Cited by 1 | Viewed by 1765

Abstract

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators [...] Read more.

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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13 pages, 616 KiB  

Open AccessArticle

New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study

by Noémi Ricard, Lelia Zebali, Cécile Renard, Marie-Pierre Goutagny, Sarah Benezech, Yves Bertrand, Michael Philippe and Carine Domenech

Cancers 2023, 15(7), 2107; https://doi.org/10.3390/cancers15072107 - 31 Mar 2023

Cited by 1 | Viewed by 1505

Abstract

Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local [...] Read more.

Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years. Full article

(This article belongs to the Topic Myeloma and Leukemia-Challenges and Current Treatment Options)

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