Danielle Brander

Positions:

Assistant Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2007

Duke University School of Medicine

Resident, Internal Medicine

Duke University School of Medicine

Grants:

A Phase 1, Open-label, study of Voruciclib in Subjects with Relapsed and/or Refractory B Cell Malignancies after failure of prior standard therapies

Administered By
Duke Cancer Institute
Awarded By
MEI Pharma, Inc.
Role
Principal Investigator
Start Date
End Date

TP-0903-102 A Combined Phase 1/2 Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of TP-0903 in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)

Administered By
Duke Cancer Institute
Awarded By
Tolero Pharmaceuticals, Inc
Role
Principal Investigator
Start Date
End Date

BGB-3111-304 An International, Phase 3, Open-label, Randomized Study of BGB-3111 Compared with Bendamustine plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Administered By
Duke Cancer Institute
Awarded By
BeiGene, Ltd
Role
Principal Investigator
Start Date
End Date

Phase 1a/1b Study of a Novel BTK Inhibitor, DTRMWXHS-12, and Combination Products, CTRM-505 and DTRM-555, in Patients with Chronic Lymphocytic Leukemia or Other B-Cell Lymphomas

Administered By
Duke Cancer Institute
Awarded By
Zhejiang DTRM Biopharma Co.Ltd.
Role
Principal Investigator
Start Date
End Date

An Open Label Compassionate Use Trial of Ublituximab and TGR-1202 in Combination or as Single Agents in Subjects Currently receiving Treatment on Ublituximab and/or TGR-1202 Trials with B-cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia.

Administered By
Duke Cancer Institute
Awarded By
TG Therapeutics, Inc
Role
Principal Investigator
Start Date
End Date

Publications:

Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families.

Chronic lymphocytic lymphoma (CLL) has one of the highest familial risks among cancers. Monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, has a higher prevalence (13%-18%) in families with 2 or more members with CLL compared with the general population (5%-12%). Although, the rate of progression to CLL for high-count MBLs (clonal B-cell count ≥500/µL) is ∼1% to 5%/y, no low-count MBLs have been reported to progress to date. We report the incidence and natural history of MBL in relatives from CLL families. In 310 CLL families, we screened 1045 relatives for MBL using highly sensitive flow cytometry and prospectively followed 449 of them. MBL incidence was directly age- and sex-adjusted to the 2010 US population. CLL cumulative incidence was estimated using Kaplan-Meier survival curves. At baseline, the prevalence of MBL was 22% (235/1045 relatives). After a median follow-up of 8.1 years among 449 relatives, 12 individuals progressed to CLL with a 5-year cumulative incidence of 1.8%. When considering just the 139 relatives with low-count MBL, the 5-year cumulative incidence increased to 5.7%. Finally, 264 had no MBL at baseline, of whom 60 individuals subsequently developed MBL (2 high-count and 58 low-count MBLs) with an age- and sex-adjusted incidence of 3.5% after a median of 6 years of follow-up. In a screening cohort of relatives from CLL families, we reported progression from normal-count to low-count MBL to high-count MBL to CLL, demonstrating that low-count MBL precedes progression to CLL. We estimated a 1.1% annual rate of progression from low-count MBL, which is in excess of that in the general population.
Authors
Slager, SL; Lanasa, MC; Marti, GE; Achenbach, SJ; Camp, NJ; Abbasi, F; Kay, NE; Vachon, CM; Cerhan, JR; Johnston, JB; Call, TG; Rabe, KG; Kleinstern, G; Boddicker, NJ; Norman, AD; Parikh, SA; Leis, JF; Banerji, V; Brander, DM; Glenn, M; Ferrajoli, A; Curtin, K; Braggio, E; Shanafelt, TD; McMaster, ML; Weinberg, JB; Hanson, CA; Caporaso, NE
MLA Citation
Slager, Susan L., et al. “Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families.Blood, vol. 137, no. 15, Apr. 2021, pp. 2046–56. Pubmed, doi:10.1182/blood.2020006322.
URI
https://scholars.duke.edu/individual/pub1473088
PMID
33512457
Source
pubmed
Published In
Blood
Volume
137
Published Date
Start Page
2046
End Page
2056
DOI
10.1182/blood.2020006322

Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial.

BACKGROUND: Patients with chronic lymphocytic leukaemia and high-risk features have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, to ibrutinib therapy in this population. METHODS: We did a randomised, phase 3, multicentre study (GENUINE) of patients aged 18 years or older with relapsed or refractory chronic lymphocytic leukaemia with at least one of 17p deletion, 11q deletion, or TP53 mutation, at 119 clinics in the USA and Israel. Eligible patients had received at least one previous chronic lymphocytic leukaemia therapy and had an Eastern Cooperative Oncology Group performance status of 2 or lower. We randomised patients (1:1) using permuted block randomisation with a block size of four and stratified by previous lines of therapy (one vs two or more) to receive ibrutinib alone or ibrutinib in combination with ublituximab. Treatment allocation was not masked to patients or investigators. Ibrutinib was given orally daily at 420 mg for all cycles. Ublituximab was given intravenously in 28-day cycles, with increasing doses during cycle 1 (≤150 mg on day 1, 750 mg on day 2, and 900 mg on days 8 and 15) and continuing at 900 mg on day 1 of cycles 2-6. After cycle 6, ublituximab was given at 900 mg every three cycles. The study was initially designed with co-primary endpoints of progression-free survival and overall response rate but due to protracted patient accrual, the protocol was amended to have a single primary endpoint of independent review committee-assessed overall response rate (defined as the proportion of patients who had a partial response, complete response, or complete response with incomplete marrow recovery according to the 2008 International Workshop on CLL criteria) in the intention-to-treat population. Safety was evaluated in the population of patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02301156, and the final analysis is presented. FINDINGS: 224 patients were assessed for eligibility, of whom 126 patients were enrolled and randomly assigned to receive ublituximab plus ibrutinib (n=64) or ibrutinib alone (n=62) between Feb 6, 2015, and Dec 19, 2016. After a median follow-up of 41·6 months (IQR 36·7-47·3), the overall response rate was 53 (83%) of 64 patients in the ublituximab plus ibrutinib group and 40 (65%) of 62 patients in the ibrutinib group (p=0·020). 117 patients, including 59 in the ublituximab plus ibrutinib group and 58 in the ibrutinib group, received at least one dose of treatment and were included in safety analyses. Most adverse events were grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and seven [12%] in the ibrutinib group), anaemia (five [8%] and five [9%]), and diarrhoea (six [10%] and three [5%]). The most common serious adverse events were pneumonia (six [10%] in the ublituximab plus ibrutinib group and four [7%] in the ibrutinib group), atrial fibrillation (four [7%] and one [2%]), sepsis (four [7%] and one [2%]), and febrile neutropenia (three [5%] and one [2%]). Two patients in the ublituximab plus ibrutinib group died due to adverse events (one cardiac arrest and one failure to thrive), neither of which were treatment-related. Five patients in the ibrutinib group died due to adverse events, including one cardiac arrest, one cerebral infarction, one intracranial haemorrhage, one Pneumocystis jirovecii pneumonia infection, and one unexplained death; the death due to cardiac arrest was considered to be treatment-related. INTERPRETATION: The addition of ublituximab to ibrutinib resulted in a statistically higher overall response rate without affecting the safety profile of ibrutinib monotherapy in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia. These findings provide support for the addition of ublituximab to Bruton tyrosine kinase inhibitors for the treatment of these patients. FUNDING: TG Therapeutics.
Authors
Sharman, JP; Brander, DM; Mato, AR; Ghosh, N; Schuster, SJ; Kambhampati, S; Burke, JM; Lansigan, F; Schreeder, MT; Lunin, SD; Zweibach, A; Shtivelband, M; Travis, PM; Chandler, JC; Kolibaba, KS; Sportelli, P; Miskin, HP; Weiss, MS; Flinn, IW
MLA Citation
Sharman, Jeff P., et al. “Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial.Lancet Haematol, vol. 8, no. 4, Apr. 2021, pp. e254–66. Pubmed, doi:10.1016/S2352-3026(20)30433-6.
URI
https://scholars.duke.edu/individual/pub1477680
PMID
33631112
Source
pubmed
Published In
The Lancet Haematology
Volume
8
Published Date
Start Page
e254
End Page
e266
DOI
10.1016/S2352-3026(20)30433-6

Comparative analysis of targeted novel therapies in relapsed, refractory chronic lymphocytic leukaemia.

Authors
Eyre, TA; Lamanna, N; Roeker, LE; Ujjani, CS; Hill, BT; Barr, PM; Lansigan, E; Cheson, BD; Yazdy, M; Allan, JN; Rhodes, J; Schuster, SJ; Nabhan, C; Skarbnik, A; Leslie, L; Islam, P; Whitaker, K; Coombs, CC; Tuncer, HH; Pagel, JM; Jacobs, R; Winter, AM; Bailey, N; Sitlinger, A; Schuh, AH; Follows, G; Fox, CP; Brander, DM; Shadman, M; Mato, AR
MLA Citation
Eyre, Toby A., et al. “Comparative analysis of targeted novel therapies in relapsed, refractory chronic lymphocytic leukaemia.Haematologica, vol. 106, no. 1, Jan. 2021, pp. 284–87. Pubmed, doi:10.3324/haematol.2019.241539.
URI
https://scholars.duke.edu/individual/pub1432815
PMID
32079693
Source
pubmed
Published In
Haematologica
Volume
106
Published Date
Start Page
284
End Page
287
DOI
10.3324/haematol.2019.241539

Managing toxicities of phosphatidylinositol-3-kinase (PI3K) inhibitors.

Despite the proven effective approach to targeting the phosphatidylinositol-3-kinase (PI3K) pathway in B-cell malignancies, the approved PI3K inhibitors idelalisib and duvelisib have been less commonly selected for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), given the availability of other more tolerable agents. However, patients with CLL/SLL can experience a disease course that is multiply relapsed, refractory, or intolerant to treatment, and PI3K inhibitors can achieve meaningful responses. This article reviews the common early- and late-onset (considered immune-mediated) toxicities with PI3K inhibitors, including infections, hepatotoxicity, diarrhea and/or colitis, and pneumonitis. Data on pretreatment considerations, toxicity management, and drug rechallenge are presented. In addition, next-generation PI3K inhibitors and novel treatment approaches with PI3K inhibitors, including combinations, time-limited treatments, and intermittent dosing, are highlighted.
Authors
Hanlon, A; Brander, DM
MLA Citation
Hanlon, Ashley, and Danielle M. Brander. “Managing toxicities of phosphatidylinositol-3-kinase (PI3K) inhibitors.Hematology Am Soc Hematol Educ Program, vol. 2020, no. 1, Dec. 2020, pp. 346–56. Pubmed, doi:10.1182/hematology.2020000119.
URI
https://scholars.duke.edu/individual/pub1469702
PMID
33275709
Source
pubmed
Published In
Hematology Am Soc Hematol Educ Program
Volume
2020
Published Date
Start Page
346
End Page
356
DOI
10.1182/hematology.2020000119

Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study.

Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.
Authors
Cuneo, A; Mato, AR; Rigolin, GM; Piciocchi, A; Gentile, M; Laurenti, L; Allan, JN; Pagel, JM; Brander, DM; Hill, BT; Winter, A; Lamanna, N; Tam, CS; Jacobs, R; Lansigan, F; Barr, PM; Shadman, M; Skarbnik, AP; Pu, JJ; Sehgal, AR; Schuster, SJ; Shah, NN; Ujjani, CS; Roeker, L; Orlandi, EM; Billio, A; Trentin, L; Spacek, M; Marchetti, M; Tedeschi, A; Ilariucci, F; Gaidano, G; Doubek, M; Farina, L; Molica, S; Di Raimondo, F; Coscia, M; Mauro, FR; de la Serna, J; Medina Perez, A; Ferrarini, I; Cimino, G; Cavallari, M; Cucci, R; Vignetti, M; Foà, R; Ghia, P; GIMEMA, European Research Initiative (ERIC) on CLL, US study group,
URI
https://scholars.duke.edu/individual/pub1461832
PMID
32969597
Source
pubmed
Published In
Cancer Medicine
Volume
9
Published Date
Start Page
8468
End Page
8479
DOI
10.1002/cam4.3470