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:

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial.

BACKGROUND: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL. METHODS: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0-2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine-rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m2 of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m2 of body surface area on day 1 of cycles 2-6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment. FINDINGS: Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine-rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7-29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable [NE] to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 [95% CI 0·28 to 0·63]; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 [11%] of 240 patients in group A, 116 [51%] of 227 in group B, and 17 [15%] of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four [2%] of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each [1%] of 227 patients in group B). INTERPRETATION: Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL. FUNDING: BeiGene.
Authors
Tam, CS; Brown, JR; Kahl, BS; Ghia, P; Giannopoulos, K; Jurczak, W; Šimkovič, M; Shadman, M; Österborg, A; Laurenti, L; Walker, P; Opat, S; Chan, H; Ciepluch, H; Greil, R; Tani, M; Trněný, M; Brander, DM; Flinn, IW; Grosicki, S; Verner, E; Tedeschi, A; Li, J; Tian, T; Zhou, L; Marimpietri, C; Paik, JC; Cohen, A; Huang, J; Robak, T; Hillmen, P
MLA Citation
Tam, Constantine S., et al. “Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial.Lancet Oncol, vol. 23, no. 8, Aug. 2022, pp. 1031–43. Pubmed, doi:10.1016/S1470-2045(22)00293-5.
URI
https://scholars.duke.edu/individual/pub1526221
PMID
35810754
Source
pubmed
Published In
Lancet Oncol
Volume
23
Published Date
Start Page
1031
End Page
1043
DOI
10.1016/S1470-2045(22)00293-5

NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.
Authors
Wierda, WG; Brown, J; Abramson, JS; Awan, F; Bilgrami, SF; Bociek, G; Brander, D; Chanan-Khan, AA; Coutre, SE; Davis, RS; Eradat, H; Fletcher, CD; Gaballa, S; Ghobadi, A; Hamid, MS; Hernandez-Ilizaliturri, F; Hill, B; Kaesberg, P; Kamdar, M; Kaplan, LD; Khan, N; Kipps, TJ; Ma, S; Mato, A; Mosse, C; Schuster, S; Siddiqi, T; Stephens, DM; Ujjani, C; Wagner-Johnston, N; Woyach, JA; Ye, JC; Dwyer, MA; Sundar, H
MLA Citation
Wierda, William G., et al. “NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022.J Natl Compr Canc Netw, vol. 20, no. 6, June 2022, pp. 622–34. Pubmed, doi:10.6004/jnccn.2022.0031.
URI
https://scholars.duke.edu/individual/pub1525092
PMID
35714675
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
20
Published Date
Start Page
622
End Page
634
DOI
10.6004/jnccn.2022.0031

Treatment outcomes with purine nucleoside analog alone or with rituximab for hairy cell leukemia at first relapse.

INTRODUCTION: Frontline treatment of hairy cell leukemia (HCL) with a single course of the purine nucleoside analog (PNA) produces a high rate of complete remission (CR) with prolonged durations. At the time of relapse, although treatment guidelines recommend re-treatment with a PNA alone or in combination with rituximab (R), practice patterns vary and data supporting each approach are limited. METHODS: We conducted a multisite outcomes analysis of patients treated for HCL between 1995 and 2018 at six US medical centers. All patients were treated with frontline PNA and subsequently required treatment with a PNA alone (PNA) or with R (+R). RESULTS: Of the 88 patients analyzed, 56 (63.6%) received second-line PNA and 22 (36.4%) received a PNA + R. Baseline characteristics of both groups were similar. There was no difference in median PFS [67 months (95% CI 43.8 non-reached (NR)) vs. 65 months (95% CI 60-NR)] or 5-year OS [98% (95% CI 0.94-1) vs. 94% (95% CI 0.83-1), p = .104] in the PNA versus PNA + R cohorts, respectively. CONCLUSION: To our knowledge, this is the largest study evaluating the role of R in treatment of relapsed HCL and suggests that there is no advantage to the addition of R to PNA therapy at the time of first re-treatment.
Authors
Hu, R; Wei, W; Mian, A; Gonter-Aubin, K; Kabel, C; Mato, A; Stephens, DM; Hanlon, A; Khajavian, S; Shadman, M; Brander, D; Madanat, Y; Park, JH; Tallman, M; Pinilla-Ibarz, J; Hill, BT
MLA Citation
Hu, Rachel, et al. “Treatment outcomes with purine nucleoside analog alone or with rituximab for hairy cell leukemia at first relapse.Eur J Haematol, vol. 108, no. 5, May 2022, pp. 379–82. Pubmed, doi:10.1111/ejh.13744.
URI
https://scholars.duke.edu/individual/pub1509898
PMID
35043475
Source
pubmed
Published In
Eur J Haematol
Volume
108
Published Date
Start Page
379
End Page
382
DOI
10.1111/ejh.13744

Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: "What's Past Is Prologue" (Shakespeare).

The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes. Symptomatic patients previously treated with a BTK inhibitor (BTKi) and venetoclax represent a new and rapidly growing unmet need in CLL. Here, we define unmet needs in a modern treatment context. We also critically review the literature for PI3K inhibitors and chemoimmunotherapy and lack of data to support their utility following BTKis and venetoclax. Finally, we suggest opportunities to ensure the continued innovation for patients with CLL.
Authors
Mato, AR; Davids, MS; Sharman, J; Roeker, LE; Kay, N; Kater, AP; Rogers, K; Thompson, MC; Rhodes, J; Goy, A; Skarbnik, A; Schuster, SJ; Tam, CS; Eyre, TA; O'Brien, S; Nabhan, C; Lamanna, N; Sun, C; Shadman, M; Pagel, JM; Ujjani, C; Brander, D; Coombs, CC; Jain, N; Cheah, CY; Brown, JR; Seymour, JF; Woyach, JA
MLA Citation
Mato, Anthony R., et al. “Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: "What's Past Is Prologue" (Shakespeare).Clin Cancer Res, vol. 28, no. 4, Feb. 2022, pp. 603–08. Pubmed, doi:10.1158/1078-0432.CCR-21-1237.
URI
https://scholars.duke.edu/individual/pub1501822
PMID
34789482
Source
pubmed
Published In
Clinical Cancer Research
Volume
28
Published Date
Start Page
603
End Page
608
DOI
10.1158/1078-0432.CCR-21-1237

Integrated safety analysis of umbralisib, a dual PI3Kδ/CK1ε inhibitor, in relapsed/refractory lymphoid malignancies.

Phosphoinositide 3-kinase-δ (PI3Kδ) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kδ and casein kinase-1ε (CK1ε). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n = 147]; marginal zone lymphoma [n = 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n = 74]; chronic lymphocytic leukemia [n = 43]; and other tumor types [n = 25]) who were treated with the recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1 months), and 107 patients (28.8%) received umbralisib for ≥12 months. Any-grade treatment-emergent adverse events (AEs) occurred in 366 (98.7%) of 371 patients, with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade 3 or higher treatment-emergent AEs occurred in 189 (50.9%) of 371 patients and included neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferase levels (5.7%). Treatment-emergent serious AEs occurred in 95 (25.6%) of 371 patients. AEs of special interest were limited and included pneumonia (29 of 371 [7.8%]), noninfectious colitis (9 of 371 [2.4%]), and pneumonitis (4 of 371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died of AEs, none of which was deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies.
Authors
Davids, MS; O'Connor, OA; Jurczak, W; Samaniego, F; Fenske, TS; Zinzani, PL; Patel, MR; Ghosh, N; Cheson, BD; Derenzini, E; Brander, DM; Reeves, JA; Knopińska-Posłuszny, W; Allan, JN; Phillips, T; Caimi, PF; Lech-Maranda, E; Burke, JM; Agajanian, R; Pettengell, R; Leslie, LA; Cheah, CY; Fonseca, G; Essell, J; Chavez, JC; Pagel, JM; Sharman, JP; Hsu, Y; Miskin, HP; Sportelli, P; Weiss, MS; Flinn, IW
MLA Citation
Davids, Matthew S., et al. “Integrated safety analysis of umbralisib, a dual PI3Kδ/CK1ε inhibitor, in relapsed/refractory lymphoid malignancies.Blood Adv, vol. 5, no. 23, Dec. 2021, pp. 5332–43. Pubmed, doi:10.1182/bloodadvances.2021005132.
URI
https://scholars.duke.edu/individual/pub1497552
PMID
34547767
Source
pubmed
Published In
Blood Adv
Volume
5
Published Date
Start Page
5332
End Page
5343
DOI
10.1182/bloodadvances.2021005132