• Researcher Profile

    Paul G. Richardson, MD

     
    Paul G. Richardson, MD

    Top Doctor

     
    Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center

    Professor of Medicine, Harvard Medical School

    Center/Program

    Hematologic Oncology

    Office phone: 617-632-2127
    Fax: 617-632-6624
    Email: paul_richardson@dfci.harvard.edu

    Preferred contact method: email

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    Research Department

    Medical Oncology/Hematologic Malignancies

    Interests

    Multiple myeloma, Stem cell transplantation, Regimen-related toxicity, Experimental therapeutics and cancer pharmacology, Non-myeloid injury including VOD and mucocytis in bone marrow transplantation

    Area of Research

    Research in Multiple Myeloma, Reduction of Regimen-Related Toxicity

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 1B07
    Boston, MA 02215

    Biography

    After comprehensive training and certification in Internal Medicine, Hematology and Medical Oncology, as well as then acquiring additional expertise in Cancer Pharmacology and transplant at Dana Farber Cancer Institute from 1994 onwards, I joined the Division of Hematologic Oncology and the Jerome Lipper Multiple Myeloma Center in December 1999. I was appointed Clinical Director of the Myeloma Center in January 2001 and have since led several novel, biologically-derived translational efforts in multiple myeloma under the overall direction and mentorship of Kenneth Anderson, M.D. These have been focused in the clinical study of new drugs in the Phase 1, 2 and 3 settings as principal investigator and first author of derived manuscripts; specifically thalidomide, the thalidomide analog lenalidomide [Revlimid], and the first-in-class proteasome inhibitor, bortezomib [Velcade]. Subsequent studies have focused on other novel agents including 2- methoxy estradiol [also known as 2-ME2], histone deacelytase inhibitors (including SAHA, also known as vorinostat) and the HSP-90 inhibitor,17-AAG, also known as tanespimicin, as well as other small molecules, including perifosine and the second generation proteasome inhibitors, NPI 0052 and MLNM 9708, as well as the newest immunomodulatory agent, pomalidomide . My most recent translational clinical innovation has been the combination of lenalidomide, bortezomib and dexamethasone (also known as RVD) first combined in our phase I trial in relapsed disease and now established in the upfront setting as a potential landmark regimen, which is currently under investigation in several multicenter phase III studies. My senior investigator role in the VISTA trial comparing bortezomib in combination with melphalan and prednisone versus melphalan and prednisone alone as part of an international team has proven to be especially productive, as this has been a highly successful study establishing bortezomib, melphalan, and prednisone as a new treatment standard in patients not eligible for stem cell transplant.

    Currently, I am leading multiple efforts studying the use of combination therapies predominantly in relapsed and refractory myeloma, an area of primary interest to me. I also serve as a principal investigator and study chairman for several clinical trials relating to other areas of myeloma treatment, including the use of combination therapies in earlier disease designed to target resistance and reduce toxicity. My major leadership efforts are focused on the IFM/DFCI upfront study in patients eligible for stem cell transplant in combination with RVD. Finally, an important new area of interest for me is treatment-emergent neuropathy in myeloma, its characterization and strategies to minimize it.

    My other substantive contribution in the area of treatment- related toxicity has been in the development of Defibrotide for the treatment of hepatic veno-occlusive disease (VOD), complicating stem cell transplant, as well as its development as a broader therapeutic adjuvant in anti-neoplastic therapy.

    As a clinical researcher in myeloma and transplant, I have published 200 original articles and over 90 reviews, chapters, and editorials in peer-reviewed journals including the New England Journal of Medicine, Blood, Journal of Clinical Oncology, Leukemia, Clinical Cancer Research, and British Journal of Haematology, as well as made numerous presentations with accompanying monographs both nationally and internationally in the context of both education and research.

    Recent Awards

    • Biochemistry Slot Prize,
      Hungarian Prize,
      Honours Colors,
      Wheelwrights Prize,
      Ver Heyden de Lancy Prize: Joint Winner,
      Emil Frei III Fellowship Award,
      Lee Beckenstein Fellowship Award,
      The Society of Teaching Scholars,
      George Canellos Award for Excellence in Clinical Research and Patient Care,
      Partners in Excellence Award,
      Medical Book Competition Award for Multiple Myeloma,
      Tisch Family Outstanding Achievement Award in Translational Research,
      Compassionate Caregiver Award,
      Fellow of the Royal College of Physicians
      , 1983 1986 1986 1986 1986 1995 1997 2002 2004 2004,2005 2005 2008 2008 2009

    Research

    Research in Multiple Myeloma, Reduction of Regimen-Related Toxicity

    Under the overall direction and mentorship of Dr. Kenneth Anderson, we are leading several translational efforts in multiple myeloma, including phase I, II, and III clinical trials of new drugs: thalidomide, the thalidomide analog IMiD 3 (also known as lenalidomide, CC-5013, or Revlimid), 2- methoxy estradiol (2-ME2), and the proteasome inhibitor PS 341 (bortezomib or Velcade). Subsequent studies have focused on other novel agents including the histone deacetylase inhibitor SAHA and derivatives of the HSP-90 inhibitor 17-AAG, as well as other small molecules. Our most recent translational research is a phase I trial of the combination of novel agents lenalidomide and bortezomib.

    In addition to research in myeloma, we have been involved in regimen-related toxicities (RRT), and in particular the development of defibrotide as a novel therapy for hepatic veno-occlusive disease. This work has led to further research in syndromes characterized by endothelial cell injury during high-dose therapy and the study of vascular damage affecting other organ structures, including mucosa. Another important new area of interest in RRT is treatment-emergent neuropathy in myeloma.

    Select Publications

    • Richardson P, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski R, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine D, Kauffman M, Adams J, Schenkein D, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;349:1287-8.
    • Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487-98.
    • Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J, Martin PL, Steinbach G, Murray KF, Vogelsang GB, Chen AR, Krishnan A, Kernan NA, Avigan DE, Spitzer TR, Shulman HM, Di Salvo DN, Revta C, Warren D, Momtaz P, Bradwin G, Wei LJ, Iacobelli M, McDonald GB, Guinan EC. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multi-organ failure post stem cell transplantation: a multi-center, randomized, dose-finding trial. Blood and Bone Marrow Transplant. Epub February 17, 2010 [in press]
    • Richardson PG, Weller E, Longial S, Jakubowiak J, Jagannath S, Raje N, Avigan D, Xie W, Ghobrial I, Schlossman R, Mazumder A, Munshi N, Vesole DH, Joyce R, Kaufman J, Doss D, Warren D, Lunde L, Kaster SK, Delaney CC, Hideshima T, Mitsiades C, Knight R, Esseltine DL, Anderson KC. Lenalidomide, Bortezomib, and Dexamethasone Combination Therapy in Patients with Newly Diagnosed Multiple Myeloma. Blood 2010, in press.
    • Coppell JA*, Richardson PG*, Soiffer R, Martin PL, Kernan NA, Chen A, Guinan E, Vogelsang G, Krishnan A, Giralt S, Revta C, Carreau NA, Iacobelli M, Carreras E, Ruutu T, Barbui T, Antin JH, Niederwieser D. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course and outcome. Biology of Blood and Marrow Transplantation, 2010; 16(2):157-168.
    • Richardson P, Jagannath S, Hussein M, Berenson J, Singhal S, Irwin D, Williams SF, Bensinger WI, Badros AZ, Vescio R, Kenvin L, Yu Z, Olesnyckyj M, Zeldis J, Knight R, and Anderson KC: The safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009; 114: 772-8.
    • Richardson P, Jagannath S, Hussein M, Berenson J, Singhal S, Irwin D, Williams SF, Bensinger WI, Badros AZ, Vescio R, Kenvin L, Yu Z, Olesnyckyj M, Zeldis J, Knight R, and Anderson KC: The safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009; 114: 772-8.
    • Richardson PG, Weller E, Jagannath S, Avigan DE, Alsina M, Schlossman R, Mazumder A, Munshi NC, Ghobrial I, Doss D, Warren DL, Lunde LE, McKenney M, Delaney C, Mitsiades CS, Hideshima T, Dalton W, Knight R, Esseltine D, Anderson KC. Lenalidomide plus bortezomib for relapsed and relapsed, refractory multiple myeloma: results of a multicenter phase 1 dose-escalation trial. J Clin Oncol. 2009;27(34):5713-9.
    • Richardson PG, Xie W, Mitsiades CS, Chanan-Khan AA, Lonial S, Hassoun H, Avigan DE, Oaklander AL, Kuter D, Wen PY, Kesari S, Briemberg HR, Schlossman RL, Munshi N, Heffner LT, Doss D, Esseltine D, Weller E, Anderson KC, Amato A. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. Journal of Clinical Oncology, 2009 ;27(21):3518-25.
    • Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D, Kinchla NM, Neuberg D, Waller EK, Antin JH, Soiffer R, Vredenburgh J, Lill M, Woolfrey AE, Bearman SI, Iacobelli M, Fareed J, Guinan EC. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high risk population. Blood 1998; 92: 737-44.
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