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Article ; Online: Treatment of Richter's Transformation with Novel Therapies.

Bajwa, Amneet / Habib, Alma / Kittai, Adam S

2024 Volume 19, Issue 2, Page(s) 45–55

Abstract: Purpose of review: This review presents recently published clinical trial data and ongoing investigations regarding the treatment of Richter's transformation (RT).: Recent findings: Recently, numerous approaches have been investigated for the ... ...

Abstract	Purpose of review: This review presents recently published clinical trial data and ongoing investigations regarding the treatment of Richter's transformation (RT). Recent findings: Recently, numerous approaches have been investigated for the treatment of RT including: traditional chemoimmunotherapy regimens combined with targeted agents such as BTKi and BCL2i; immunotherapy combined with targeted agents; non-covalent BTKis; bispecific T cell engagers; and CART therapy. In addition, various novel targeted agents are currently being studied for the treatment of RT in phase 1 and 2 clinical trials. Standard of care treatment with chemoimmunotherapy for RT has limited efficacy in achieving durable remissions. Here, we review recent data on the use of combination treatments and targeted agents in RT. Although some progress has been made in the investigation to optimize treatment of RT, further study is needed to evaluate long term outcomes of recently published trials and test efficacy of upcoming novel agents.
MeSH term(s)	Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Immunotherapy
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2229765-0
ISSN	1558-822X ; 1558-8211
ISSN (online)	1558-822X
ISSN	1558-8211
DOI	10.1007/s11899-023-00721-8
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Article ; Online: uMRD: "the" endpoint or "an" endpoint for CLL?

Kittai, Adam S / Woyach, Jennifer A

Blood

2022 Volume 140, Issue 8, Page(s) 797–798

MeSH term(s)	Bridged Bicyclo Compounds, Heterocyclic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; Neoplasm Recurrence, Local ; Rituximab ; Sulfonamides
Chemical Substances	Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides ; Rituximab (4F4X42SYQ6) ; venetoclax (N54AIC43PW)
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016927
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Zs.MO 364: Show issues

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Article ; Online: Richter's Transformation.

Sigmund, Audrey M / Kittai, Adam S

Current oncology reports

2022 Volume 24, Issue 8, Page(s) 1081–1090

Abstract: Purpose of review: Richter's transformation (RT) occurs when chronic (CLL) transforms into an aggressive lymphoma. Despite improvements in the treatment of CLL, prognosis for RT remains poor. Here, we review current literature of RT, with a focus on ... ...

Abstract	Purpose of review: Richter's transformation (RT) occurs when chronic (CLL) transforms into an aggressive lymphoma. Despite improvements in the treatment of CLL, prognosis for RT remains poor. Here, we review current literature of RT, with a focus on novel treatment options. Recent findings: Efforts are underway to improve outcomes for patients with RT. While small molecule inhibitors have limited efficacy as monotherapy, recent developments combining them with chemo-immunotherapy show promise. Studies exploring the use of cellular therapies including chimeric antigen receptor T-cells and bispecific antibodies are ongoing. The current treatment paradigm for RT is to enroll these patients on a clinical trial when available, together with consultation for a consolidative allogeneic stem cell transplant. Trials investigating novel combinations and cellular therapy are ongoing. Determining predictive variables of transformation is imperative to design studies that allow for early identification and intervention for patients with RT.
MeSH term(s)	Cell Transformation, Neoplastic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Lymphoma, Large B-Cell, Diffuse/pathology ; Prognosis ; Stem Cell Transplantation
Language	English
Publishing date	2022-04-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057359-5
ISSN	1534-6269 ; 1523-3790
ISSN (online)	1534-6269
ISSN	1523-3790
DOI	10.1007/s11912-022-01274-4
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Zs.A 5521: Show issues

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Article ; Online: Glabellar and auricular leukemia cutis in CLL.

Steinman, Bradley / Plaza, Jose A / Kittai, Adam S

EJHaem

2022 Volume 3, Issue 4, Page(s) 1398–1399

Language	English
Publishing date	2022-08-28
Publishing country	United States
Document type	Journal Article
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.538
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Article ; Online: Comparison of karyotype scoring guidelines for evaluating karyotype complexity in chronic lymphocytic leukemia.

Avenarius, Matthew R / Huang, Ying / Kittai, Adam S / Bhat, Seema A / Rogers, Kerry A / Grever, Michael R / Woyach, Jennifer A / Miller, Cecelia R

Leukemia

2024 Volume 38, Issue 3, Page(s) 676–678

MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Karyotyping ; Karyotype
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Letter
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-024-02177-y
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Zs.A 2295: Show issues

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Article ; Online: Cellular Therapy Advances in Chronic Lymphocytic Leukemia and Richter's Syndrome.

Bajwa, Amneet / Voorhees, Timothy J / Kittai, Adam S

Current problems in cancer

2021 Volume 46, Issue 1, Page(s) 100827

Abstract: Over the past 10 years, there have been great treatment advances for chronic lymphocytic leukemia (CLL) with the development of small molecule inhibitors. However, there remains an area of unmet need for patients who progress on novel therapies. The ... ...

Abstract	Over the past 10 years, there have been great treatment advances for chronic lymphocytic leukemia (CLL) with the development of small molecule inhibitors. However, there remains an area of unmet need for patients who progress on novel therapies. The development of cellular therapies in CLL has been hindered by CLL induced immunosuppression. Fortunately, recent progress in various methods in immunomodulation may help overcome this limitation in CLL. These advances have spurred ongoing interest in the development of cellular therapies for CLL, including chimeric antigen receptor (CAR) T cell therapies, bi-specific antibodies, and use of natural killer cells. These novel treatment modalities may hold promise for patients with refractory, and potentially transformed disease. Here, we discuss the development of CAR-T cell therapy in CLL and the impact of combining CAR-T and small molecule inhibitors on treatment outcomes, the evolving role of bi-specific antibodies and natural killer cells, and comment on the use of cellular therapies for Richter's syndrome.
MeSH term(s)	Cell- and Tissue-Based Therapy ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Lymphoma, Large B-Cell, Diffuse ; Receptors, Chimeric Antigen ; Treatment Outcome
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2021-12-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	441816-5
ISSN	1535-6345 ; 0147-0272
ISSN (online)	1535-6345
ISSN	0147-0272
DOI	10.1016/j.currproblcancer.2021.100827
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Article ; Online: Resistance Mechanisms to Targeted Agents in Chronic Lymphocytic Leukemia.

Kittai, Adam S / Woyach, Jennifer A

Cancer journal (Sudbury, Mass.)

2019 Volume 25, Issue 6, Page(s) 428–435

Abstract: Agents that specifically target pathologic mechanisms of survival have now been approved for the treatment of chronic lymphocytic leukemia in both the treatment-naive and relapsed/refractory settings. These 4 agents include the Bruton tyrosine kinase ... ...

Abstract	Agents that specifically target pathologic mechanisms of survival have now been approved for the treatment of chronic lymphocytic leukemia in both the treatment-naive and relapsed/refractory settings. These 4 agents include the Bruton tyrosine kinase inhibitor ibrutinib, the B-cell leukemia/lymphoma-2 inhibitor venetoclax, and the phosphatidylinositol-3 kinase inhibitors idelalisib and duvelisib. Although clinical outcomes are improved with all of these inhibitors, acquired resistance does occur and leads to progression of disease. Resistance to targeted therapy can occur through direct mutations of the target or through the overexpression of alternative cell survival pathways not affected by the specific inhibitor. Determining which patients will develop resistance, why resistance occurs, how to overcome resistance, and when to test for resistance are all subjects of ongoing research. In this review, we describe the current data relative to the development of resistance to targeted therapies in CLL.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor ; Drug Resistance, Neoplasm/genetics ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/etiology ; Leukemia, Lymphocytic, Chronic, B-Cell/mortality ; Molecular Targeted Therapy/adverse effects ; Molecular Targeted Therapy/methods ; Prognosis ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; Protein Kinase Inhibitors
Language	English
Publishing date	2019-11-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2018400-1
ISSN	1540-336X ; 1528-9117 ; 1081-4442
ISSN (online)	1540-336X
ISSN	1528-9117 ; 1081-4442
DOI	10.1097/PPO.0000000000000406
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Zs.A 4470: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 163: Show issues

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Article ; Online: Racial disparities in chronic lymphocytic leukemia/small lymphocytic lymphoma accounting for small molecule inhibitors: A real-world cohort analysis.

Kittai, Adam S / Hang, Ying / Bhat, Seema A / Clark, Abi / Grever, Michael / Rhodes, Joanna M / Roberts, Melyssa / Rogers, Kerry A / Teschemaker, Anna / Munoz-Sagastibelza, Maria / Woyach, Jennifer A / Barrientos, Jacqueline C

American journal of hematology

2024 Volume 99, Issue 4, Page(s) 780–784

Abstract: Kaplan-Meier curve depicting overall survival from CLL treatment start by race. For patients with CLL, no overall survival difference was observed between races in this real-world US database. ...

Abstract	Kaplan-Meier curve depicting overall survival from CLL treatment start by race. For patients with CLL, no overall survival difference was observed between races in this real-world US database.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; Cohort Studies
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Letter
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27241
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Article ; Online: An indirect comparison of acalabrutinib with and without obinutuzumab versus zanubrutinib in treatment-naive CLL.

Kittai, Adam S / Allan, John N / James, Dan / Bridge, Helen / Miranda, Miguel / Yong, Alan Sm / Fam, Fady / Roos, Jack / Shetty, Vikram / Skarbnik, Alan P / Davids, Matthew S

Blood advances

2024

Abstract: The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy versus zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without del(17p) were compared using an ... ...

Abstract	The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy versus zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data (IPD) from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. Post-matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR]: 0.41; 95% CI: 0.23-0.74) and comparable with acalabrutinib monotherapy (HR: 0.91; 95% CI: 0.53-1.56) versus zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension versus zanubrutinib (OR: 0.44, 95% CI: 0.20-0.99), while acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (odds ratio [OR]: 2.19; 95% CI: 1.33-3.60) and arthralgia (OR: 2.33; 95% CI: 1.37-3.96) versus zanubrutinib. No other significant differences in safety were observed. In summary, compared with zanubrutinib, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023012142
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Article ; Online: Relevance of Prognostic Factors in the Era of Targeted Therapies in CLL.

Kittai, Adam S / Lunning, Matthew / Danilov, Alexey V

Current hematologic malignancy reports

2019 Volume 14, Issue 4, Page(s) 302–309

Abstract: Purpose of review: Clinicians continue to utilize prognostic biomarkers, such as expression of CD38 and ZAP-70, IGHV mutational status, cytogenetic abnormalities, and genomic aberrations in TP53, to guide prognosis and treatment of patients with CLL. ... ...

Abstract	Purpose of review: Clinicians continue to utilize prognostic biomarkers, such as expression of CD38 and ZAP-70, IGHV mutational status, cytogenetic abnormalities, and genomic aberrations in TP53, to guide prognosis and treatment of patients with CLL. These biomarkers have been validated with standard chemoimmunotherapy. Here, we discuss whether these biomarkers maintain their prognostic significance in the era of targeted therapy. Recent findings: Multiple phase 3 clinical trials have now proven improved efficacy of targeted therapy over traditional chemoimmunotherapy. We now have ample prospective data using targeted therapy to critically evaluate whether prior prognostic biomarkers remain relevant. High-risk features do not have the same magnitude of effect on clinical outcomes in the era of targeted therapy when compared to chemoimmunotherapy. Aberrations in TP53 continue to predict inferior outcomes. More research is needed to determine what features confer poor prognosis when targeted therapy is used to treat CLL.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor ; Clinical Trials as Topic ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/etiology ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/mortality ; Molecular Targeted Therapy ; Prognosis ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor
Language	English
Publishing date	2019-04-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2229765-0
ISSN	1558-822X ; 1558-8211
ISSN (online)	1558-822X
ISSN	1558-8211
DOI	10.1007/s11899-019-00511-1
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