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:

Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK Inhibition as an Effective Strategy.

PURPOSE: Venetoclax-based therapy is a standard-of-care option in first-line and relapsed/refractory chronic lymphocytic leukemia (CLL). Patient management following venetoclax discontinuation remains nonstandard and poorly understood. EXPERIMENTAL DESIGN: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Coprimary endpoints were overall response rate (ORR) and progression-free survival for the post-venetoclax treatments stratified by treatment type [Bruton's tyrosine kinase inhibitor (BTKi), PI3K inhibitor (PI3Ki), and cellular therapies]. RESULTS: We identified patients with CLL who discontinued venetoclax in the first-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n = 130), and 81% were idelalisib naïve (n = 263). ORR to BTKi was 84% (n = 44) in BTKi-naïve patients versus 54% (n = 30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons. CONCLUSIONS: For BTKi-naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi-exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies.See related commentary by Rogers, p. 3501.
Authors
Mato, AR; Roeker, LE; Jacobs, R; Hill, BT; Lamanna, N; Brander, D; Shadman, M; Ujjani, CS; Yazdy, MS; Perini, GF; Pinilla-Ibarz, JA; Barrientos, J; Skarbnik, AP; Torka, P; Pu, JJ; Pagel, JM; Gohil, S; Fakhri, B; Choi, M; Coombs, CC; Rhodes, J; Barr, PM; Portell, CA; Parry, H; Garcia, CA; Whitaker, KJ; Winter, AM; Sitlinger, A; Khajavian, S; Grajales-Cruz, AF; Isaac, KM; Shah, P; Akhtar, OS; Pocock, R; Lam, K; Voorhees, TJ; Schuster, SJ; Rodgers, TD; Fox, CP; Martinez-Calle, N; Munir, T; Bhavsar, EB; Bailey, N; Lee, JC; Weissbrot, HB; Nabhan, C; Goodfriend, JM; King, AC; Zelenetz, AD; Dorsey, C; Bigelow, K; Cheson, BD; Allan, JN; Eyre, TA
MLA Citation
Mato, Anthony R., et al. “Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK Inhibition as an Effective Strategy.Clin Cancer Res, vol. 26, no. 14, July 2020, pp. 3589–96. Pubmed, doi:10.1158/1078-0432.CCR-19-3815.
URI
https://scholars.duke.edu/individual/pub1434672
PMID
32198151
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
3589
End Page
3596
DOI
10.1158/1078-0432.CCR-19-3815

Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.

Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones.
Authors
Sung, AD; Jauhari, S; Siamakpour-Reihani, S; Rao, AV; Staats, J; Chan, C; Meyer, E; Gadi, VK; Nixon, AB; Lyu, J; Xie, J; Bohannon, L; Li, Z; Hourigan, CS; Dillon, LW; Wong, HY; Shelby, R; Diehl, L; de Castro, C; LeBlanc, T; Brander, D; Erba, H; Galal, A; Stefanovic, A; Chao, N; Rizzieri, DA
MLA Citation
Sung, Anthony D., et al. “Microtransplantation in older patients with AML: A pilot study of safety, efficacy and immunologic effects.Am J Hematol, vol. 95, no. 6, June 2020, pp. 662–71. Pubmed, doi:10.1002/ajh.25781.
URI
https://scholars.duke.edu/individual/pub1434771
PMID
32162718
Source
pubmed
Published In
Am J Hematol
Volume
95
Published Date
Start Page
662
End Page
671
DOI
10.1002/ajh.25781

Impact of exercise on the immune system and outcomes in hematologic malignancies.

Exercise is increasingly recognized as important to cancer care. The biology of how exercise improves outcomes is not well understood, however. Studies show that exercise favorably influences the immune system in healthy individuals (neutrophils, monocytes, natural killer cells, T cells, and a number of cytokines). Thus, exercise in patients with hematologic cancer could significantly improve immune function and tumor microenvironment. We performed a literature search and identified 7 studies examining exercise and the immune environment in hematologic malignancies. This review focuses on the role of exercise and physical activity on the immune system in hematologic malignancies and healthy adults.
MLA Citation
Sitlinger, Andrea, et al. “Impact of exercise on the immune system and outcomes in hematologic malignancies.Blood Adv, vol. 4, no. 8, Apr. 2020, pp. 1801–11. Pubmed, doi:10.1182/bloodadvances.2019001317.
URI
https://scholars.duke.edu/individual/pub1440468
PMID
32343800
Source
pubmed
Published In
Blood Adv
Volume
4
Published Date
Start Page
1801
End Page
1811
DOI
10.1182/bloodadvances.2019001317

A case of CNS aspergillosis in a patient with chronic lymphocytic leukemia on first-line ibrutinib therapy.

Ibrutinib has revolutionized the treatment of chronic lymphoid malignancies. Despite its success, ibrutinib has been linked with several reports of invasive fungal infections. We present a case of CNS aspergillosis in a CLL patient on first line ibrutinib therapy. We summarize existing case reports and case series of invasive aspergillosis in patients on ibrutinib, the pathogenesis of invasive aspergillosis, and discuss the clinical controversies regarding anti-fungal prophylaxis in this population.
Authors
Eichenberger, EM; Saullo, J; Brander, D; Wang, S-H; Perfect, JR; Messina, JA
MLA Citation
Eichenberger, Emily M., et al. “A case of CNS aspergillosis in a patient with chronic lymphocytic leukemia on first-line ibrutinib therapy.Med Mycol Case Rep, vol. 27, Mar. 2020, pp. 17–21. Pubmed, doi:10.1016/j.mmcr.2019.12.007.
URI
https://scholars.duke.edu/individual/pub1424293
PMID
31879587
Source
pubmed
Published In
Medical Mycology Case Reports
Volume
27
Published Date
Start Page
17
End Page
21
DOI
10.1016/j.mmcr.2019.12.007

The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia.

Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and <75 years treated in the relapsed, refractory non-trial setting. We demonstrate that venetoclax has equivalent efficacy and safety in relapsed/refractory CLL patients who are elderly, the majority of whom are previous ibrutinib-exposed and therefore may otherwise have few clear therapeutic options.
Authors
Eyre, TA; Roeker, LE; Fox, CP; Gohill, SH; Walewska, R; Walter, HS; Forconi, F; Broom, A; Arumainathan, A; Brander, DM; Allan, JN; Schuster, SJ; Hill, BT; Lansigan, F; Cheson, BD; Lamanna, N; Coombs, CC; Barr, PM; Skarbnik, AP; Shadman, M; Ujjani, CS; Pearson, L; Pagel, JM; Jacobs, R; Mato, AR
MLA Citation
Eyre, Toby A., et al. “The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia.Br J Haematol, vol. 188, no. 6, Mar. 2020, pp. 918–23. Pubmed, doi:10.1111/bjh.16271.
URI
https://scholars.duke.edu/individual/pub1421334
PMID
31682002
Source
pubmed
Published In
Br J Haematol
Volume
188
Published Date
Start Page
918
End Page
923
DOI
10.1111/bjh.16271