David Rizzieri

Overview:

My research interests focus on the care of patients with hematologic malignancies, both with and without the use of bone marrow or stem cell transplantation. I focus my research efforts on new approaches to manipulate minimal residual disease.

Recent endeavors have included:

  1. Phase one trials with novel anti-cancer agents targeting aurora kinases, tyrosine kinases, mtor, VEGF, and raf/ras pathways 
  2. New monoclonal antibodies targeting tumor stroma rather than cellular antigens 
  3. Investigating new antibody targets, i.e. CD123, endoglin, or tenascin for hematologic malignancies 
  4. Aggressive therapy and transplantation for mantle cell lymphoma 
  5. Antiangiogenesis therapy for patients with NHL 
  6. Nonablative allogeneic transplantation therapy with matched or mismatched donors followed by immune modulation

Positions:

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. 1991

University of Rochester

Medical Resident, Medicine

Duke University

Fellow in Hematology/Oncology, Medicine

Duke University

Grants:

Mechanisms of lung injury following autologous BMT

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

SGI 110 12

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Phase 1b Study of Venetoclax and Alvocidib in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

PF-04449913 (Glasdegib) in Combination with Azacitidine

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Protocol 2215-CL-9100

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Is autologous stem cell transplantation still relevant for multiple myeloma?

PURPOSE OF REVIEW: Autologous stem cell transplantation has been the standard of care in myeloma treatment for many years, but the availability of newer antimyeloma drugs and the emerging data from chimeric antigen receptor (CAR) T-cell clinical studies make us question the relevance of it. The purpose of this review is to go over recent data and to reassess the current status of autologous stem cell transplantation as a standard of care. RECENT FINDINGS: Autologous stem cell transplantation can be safely performed for elderly patients and there is no absolute age limit. Recent data on BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan), Busulfan/Melphalan, and Carmustine/Melphalan conditioning when compared with Melphalan showed favorable survival outcomes with manageable toxicities although we need to see data from randomized, multicenter studies. Posttransplant maintenance and consolidation can maximize the benefit of transplant by prolonging progression-free survival. Current B-cell maturation antigen CAR T-cell therapy showed remarkably high response rates, but didn't seem to provide durable response yet. SUMMARY: Recent advances in myeloma therapy and autologous stem cell transplantation are described. Although we've seen many new developments including CAR T-cell therapies, autologous stem cell transplantation remains as the standard of care. However, it may be replaced by or combined with newer therapies in the future.
Authors
MLA Citation
Choi, Taewoong. “Is autologous stem cell transplantation still relevant for multiple myeloma?.” Curr Opin Hematol, vol. 26, no. 6, Nov. 2019, pp. 386–91. Pubmed, doi:10.1097/MOH.0000000000000538.
URI
https://scholars.duke.edu/individual/pub1411540
PMID
31567432
Source
pubmed
Published In
Curr Opin Hematol
Volume
26
Published Date
Start Page
386
End Page
391
DOI
10.1097/MOH.0000000000000538

Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.
Authors
Rashidi, A; Hamadani, M; Zhang, M-J; Wang, H-L; Abdel-Azim, H; Aljurf, M; Assal, A; Bajel, A; Bashey, A; Battiwalla, M; Beitinjaneh, AM; Bejanyan, N; Bhatt, VR; Bolaños-Meade, J; Byrne, M; Cahn, J-Y; Cairo, M; Ciurea, S; Copelan, E; Cutler, C; Daly, A; Diaz, M-A; Farhadfar, N; Gale, RP; Ganguly, S; Grunwald, MR; Hahn, T; Hashmi, S; Hildebrandt, GC; Holland, HK; Hossain, N; Kanakry, CG; Kharfan-Dabaja, MA; Khera, N; Koc, Y; Lazarus, HM; Lee, J-W; Maertens, J; Martino, R; McGuirk, J; Munker, R; Murthy, HS; Nakamura, R; Nathan, S; Nishihori, T; Palmisiano, N; Patel, S; Pidala, J; Olin, R; Olsson, RF; Oran, B; Ringden, O; Rizzieri, D; Rowe, J; Savoie, ML; Schultz, KR; Seo, S; Shaffer, BC; Singh, A; Solh, M; Stockerl-Goldstein, K; Verdonck, LF; Wagner, J; Waller, EK; De Lima, M; Sandmaier, BM; Litzow, M; Weisdorf, D; Romee, R; Saber, W
MLA Citation
Rashidi, Armin, et al. “Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission..” Blood Adv, vol. 3, no. 12, June 2019, pp. 1826–36. Pubmed, doi:10.1182/bloodadvances.2019000050.
URI
https://scholars.duke.edu/individual/pub1393594
PMID
31201170
Source
pubmed
Published In
Blood Adv
Volume
3
Published Date
Start Page
1826
End Page
1836
DOI
10.1182/bloodadvances.2019000050

Limitations to Receiving Allogeneic Hematopoietic Cell Transplantation for Treatment of Acute Myeloid Leukemia: A Large Multi-Center Prospective Longitudinal Observational Study

<jats:title>Abstract</jats:title> <jats:p>Introduction: Acute myeloid leukemia (AML) is most frequently diagnosed in older patients (pts), whose median survival is less than 1 year. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. However, older pts often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. To this end, we designed a prospective, multi-center, longitudinal, observational study dating from first presentation of adult pts with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred.</jats:p> <jats:p>Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including instrumental activities of daily living (IADL) and activities of daily living (ADL); frailty including walk test; geriatric assessment (GA) including cognition; Karnofsky performance status (KPS); QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale (EQ-5D), ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. High-risk myelodysplastic syndromes (MDS) receiving AML-like therapy were included.</jats:p> <jats:p>We used competing risk Cox regression analyses, treating HCT as the event of interest and death without HCT as a competing risk, with staggered entry (left truncation) at time of consent. Associations between variables were assessed both at enrollment and over time.</jats:p> <jats:p>Results: The overall rate of HCT at 9 months after enrollment was 43% (Figure 1) and 92% of pts who received HCT did so by the 9 month mark.</jats:p> <jats:p>In multivariate analyses, death without HCT (Table 2) was associated with augmented HCT-CI scores ≥5 (HR:2.11, p&lt;0.0001), age ≥50 years with those aged ≥70 years having the highest association (HR:2.71, p&lt;0.0001), ELN intermediate (HR:2.43, p=0.0003) or unfavorable risks (HR:4.3, p&lt;0.0001), receiving low-intensity induction regimens (HR:1.42, p=0.04), relapsed/refractory disease at enrollment (HR:2.04, p&lt;0.0001), dependent status per ADL scores &lt;14 (HR:1.59, p=0.005), and depression per PHQ-9 (HR:1.56, p=0.009).</jats:p> <jats:p>Among survivors (Table 3), low likelihood to receive HCT was associated with age ≥70 years (HR:0.40, p=0.0001), low ELN risk (HR:0.28, p&lt;0.0001), low-intensity induction (HR:0.56, p=0.02), poor KPS (HR:0.49, p=0.0005), and relapse after initial complete remission (CR) (HR:0.41, p=0.001); while pts with high-risk MDS (HR:2.43, p&lt;0.0001), relapsed/refractory disease at enrollment (HR:2.43, p&lt;0.0001), and CR after induction (HR:4.59, p&lt;0.0001) were more likely to receive HCT. Among pts aged ≥60 years, and after considering previous factors, impaired cognition (HR:0.45, p=0.007) and impaired hearing (HR:0.71, p=0.009) were associated with lower likelihood to receive HCT.</jats:p> <jats:p>Conclusions: In a prospective, observational, multi-center study, increasing age, comorbidity burden, ELN risk, low-intensity initial AML induction regimen, depression, and functional dependence increase risks of early mortality without HCT.</jats:p> <jats:p>In those who survived long enough to potentially receive HCT, age up to 69 years and/or multiple comorbidities were not found to be barriers to HCT, likely reflecting the widespread use of reduced-intensity conditioning regimens. However, the independent sharp decline in receipt of HCT in pts aged 70-80 years suggests continued bias, although pts in this age group have been shown to derive similar benefit from HCT as younger pts. Use of objective comorbidity and GA tools rather than age per se to decide on HCT is encouraged.</jats:p> <jats:p>The adverse impact of impairments in psychological health and function on survival and of impairments of cognition, geriatric health, and performance status on receipt of HCT emphasize the need for interventions that target these health limitations in conjunction with AML treatment to improve outcomes.</jats:p> <jats:p>Finally, the benefit of intensive vs. less-intensive induction therapies should be addressed with a randomized trial.</jats:p> <jats:p /> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Shami:Lone Star Biotherapies: Equity Ownership; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees; JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy. Rizzieri:Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang:Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Amgen: Speakers Bureau; Otsuka: Consultancy; Alexion: Consultancy, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.</jats:p> </jats:sec>
Authors
Sorror, ML; Storer, BE; Gerds, AT; Medeiros, BC; Shami, PJ; Galvin, JP; Adekola, KU; Luger, S; Baer, MR; Rizzieri, DA; Wildes, TM; Wang, ES; Faderl, S; Koprivnikar, JL; Sekeres, MA; Mukherjee, S; Smith, J; Garrison, M; Kojouri, K; Nyland, JE; Moore, RR; Fleuret, SL; Lynch, Y; Becker, PS; Percival, M-EM; Sandmaier, BM; Appelbaum, FR; Estey, EH
MLA Citation
Sorror, Mohamed L., et al. “Limitations to Receiving Allogeneic Hematopoietic Cell Transplantation for Treatment of Acute Myeloid Leukemia: A Large Multi-Center Prospective Longitudinal Observational Study.” Blood, vol. 132, no. Supplement 1, American Society of Hematology, 2018, pp. 1388–1388. Crossref, doi:10.1182/blood-2018-99-112672.
URI
https://scholars.duke.edu/individual/pub1373496
Source
crossref
Published In
Blood
Volume
132
Published Date
Start Page
1388
End Page
1388
DOI
10.1182/blood-2018-99-112672

High-dose BCNU/Melphalan conditioning regimen before autologous stem cell transplantation in newly diagnosed multiple myeloma.

Single-agent high-dose melphalan (HDM, 200 mg/m2) has been the most commonly used conditioning regimen prior to autologous stem cell transplant, since its introduction in 1992. We used a more aggressive alkylator-based conditioning regimen in an attempt to overcome early relapse and combat drug resistance. We present a retrospective comparison and long-term follow-up of newly diagnosed patients with multiple myeloma (MM) treated with induction followed by either high-dose carmustine (BCNU) and HDM, or HDM alone, both followed by autologous stem cell transplant (ASCT). Between 1997 and 2002, 104 patients were treated with BCNU/HDM; from 2001 to 2008, 103 patients were treated with HDM alone. Median follow-up of survivors was 78 and 68 months for the BCNU/HDM and HDM groups, respectively. The median PFS was significantly increased with the BCNU/HDM regimen (40.4 vs 20.5 months, P<0.001). Median overall survival was increased with the BCNU/HDM regimen when compared with HDM alone (88.4 vs 67.2 months, P=0.07), but the difference was not statistically significant. Transplant-related mortality was similar in both groups (2.9% with BCNU and HDM vs 3.9% with HDM alone). Our findings suggest that the BCNU/HDM preparative regimen should be investigated further and potentially compared in a prospective randomized manner with HDM alone.
Authors
MLA Citation
Sivaraj, D., et al. “High-dose BCNU/Melphalan conditioning regimen before autologous stem cell transplantation in newly diagnosed multiple myeloma..” Bone Marrow Transplant, vol. 53, no. 1, Jan. 2018, pp. 34–38. Pubmed, doi:10.1038/bmt.2017.208.
URI
https://scholars.duke.edu/individual/pub1284293
PMID
29084203
Source
pubmed
Published In
Bone Marrow Transplant
Volume
53
Published Date
Start Page
34
End Page
38
DOI
10.1038/bmt.2017.208

Treatment of blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4+CD56+CD123+lineage-MPO-, although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies. Chromosomal aberrations are frequent, and the mutational landscape of BPDCN is being rapidly characterized although no obvious molecular target for chemoimmunotherapy has been identified. Chemotherapy regimens developed for acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome have all been used to treat BPDCN. Relapse is frequent, and overall survival is quite poor. Allogeneic transplantation offers a chance at prolonged remission and possible cure for those who are eligible; unfortunately, relapse remains high ranging from 30% to 40%. Novel therapies such as SL-401, a diphtheria toxin conjugated to interleukin-3 (IL-3) is commonly overexpressed in BPDCN and other aggressive myeloid malignancies and has shown considerable promise in ongoing clinical trials. Future work with SL-401 will define its place in treating relapsed or refractory disease as well as its role as a first-line therapy or bridge to transplantation.
Authors
Sullivan, JM; Rizzieri, DA
MLA Citation
Sullivan, Jill M., and David A. Rizzieri. “Treatment of blastic plasmacytoid dendritic cell neoplasm..” Hematology Am Soc Hematol Educ Program, vol. 2016, no. 1, Dec. 2016, pp. 16–23. Pubmed, doi:10.1182/asheducation-2016.1.16.
URI
https://scholars.duke.edu/individual/pub1234674
PMID
27913457
Source
pubmed
Published In
Hematology Am Soc Hematol Educ Program
Volume
2016
Published Date
Start Page
16
End Page
23
DOI
10.1182/asheducation-2016.1.16