Overview of Therapy ofLymphomaAnn S. LaCasce, MDDirector, Dana-Farber/Partners CancerCare Hematology-Medical OncologyFello...
Agenda• History of lymphoma therapy• Current chemotherapy agents• Antibody based therapies• Overview of radiation• Standar...
History of lymphomachemotherapyNitrogen mustard Used to treat  HL1942   FDA approvescyclophosphamide1959 Farber treats  AL...
History of cancer
Mustard gasSoldiers exposedto mustard gashad destruction oflymphoid tissue andbone marrow
History of chemotherapy1940’s pharmacologistsGillman and Goodmanrecruited to investigatechemical warfare
First chemotherapy • Goodman and Gillman administerednitrogen mustard to mice with lymphoidtumors• In 1942, Gustav Lindsko...
Sidney FarberIn 1948, gave aminopterin(folate antagonist) leadingto first remission in a pediatricpatient with ALL
Combination chemotherapyFrei, Holland, and Freireichhypothesized strategy forcombination chemotherapybased on treatment of...
MOPP for lymphomaCanellos and DeVita – MOPP which cured patients withHodgkin and non-Hodgkin lymphoma
Chemotherapy drugsChemotherapy drugsChemotherapy drugs kill dividing cells
Side effects of chemotherapy• Kills the body’s normal rapidly dividingcells:– Bone marrow (myelosuppression)– Digestive tr...
Common classes of chemotherapyin lymphoma• Alkylators (cytoxan)• Anthracyclines(adriamycin)• Anti-metabolites(fludarabine)...
Radiation
Discovery of X-rayWilhelm Röentgen1895
Marie CurieLate 1800’sdiscovered poloniumand radium and ledfirst studies of radiationto treat cancer
External beam radiotherapy(XRT)Currently delivered via linear acceleratorsCauses cellular DNA damageUse imaging to plan...
Involved Field Radiation
Antibodies,Kinase inhibitorsNewer therapies
B-cellB-cellCD20 CD20CD20Punch holesDirect killingHow does rituximab work?Recruit immunecells
Brentuximab VedotinDrug (MMAE)Anti-CD30 antibodyBinds to CD30MMAE disruptsmicrotubule networkInternalized and goesto lysos...
Diffuse large B-cell lymphoma• CHOP (cytoxan, adriamycin, vincristine,prednisone) standard treatment since1970’s• More agg...
Indolent lymphomas• Early stage disease – radiation• Advanced stage disease:• Observation• Rituximab• Rituximab plus chemo...
Chronic lymphocytic leukemia• Observation• Rituximab plus fludarabine with or withoutcyclophosphamide• Chlorambucil with o...
Hodgkin lymphoma - chemotherapy• ABVD (adriamycin, bleomycin, vinblastine,dacarbazine)• Generally well tolerated• Typicall...
Hodgkin lymphoma - RT• Used as part of therapy for early stagedisease in some patients• Used for bulky areas in advanced d...
Novel pathways in NHL
What is a clinical trial?• Test the safety and how well a new drugworks in a particular disease• Test the safety and how w...
Clinical trials
Phase III clinical trialIn cancer studies, typically noplacebo except in certaincircumstances
Oversight clinical trials• Studies may be conducted by pharmaceuticalcompanies, single or group of investigators(including...
Summary• We’ve come a long way since nitrogenmustard• Combination chemotherapy remains part ofmany lymphoma regimens• Radi...
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An Overview of Lymphoma Treatment

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Audio and slides for this presentation are available on YouTube: http://youtu.be/rAgnoymx0DQ

Dr. Ann LaCasce talks about the various treatments for lymphoma, including chemotherapy and radiation therapy methods, as well as the role of clinical trials. This presentation was first given at a lymphoma workshop presented by the Lymphoma Research Foundation (www.lymphoma.org).

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An Overview of Lymphoma Treatment

  1. 1. Overview of Therapy ofLymphomaAnn S. LaCasce, MDDirector, Dana-Farber/Partners CancerCare Hematology-Medical OncologyFellowship Program Assistant Professor of Medicine, Harvard Medical SchoolMarch 23, 2013
  2. 2. Agenda• History of lymphoma therapy• Current chemotherapy agents• Antibody based therapies• Overview of radiation• Standard therapy– Diffuse large B-cell lymphoma– Indolent lymphoma– CLL/SLL– Hodgkin lymphoma• Clinical trials
  3. 3. History of lymphomachemotherapyNitrogen mustard Used to treat  HL1942   FDA approvescyclophosphamide1959 Farber treats  ALLwith methotrexate1948 POMP induces remissions in ALL DeVita et al cure lymphomawith combination chemo19701965 Rituximab approved     for B-cell NHL Brentuximab approved          for relapsed HL   and CD30+ T-cell NHL19972011
  4. 4. History of cancer
  5. 5. Mustard gasSoldiers exposedto mustard gashad destruction oflymphoid tissue andbone marrow
  6. 6. History of chemotherapy1940’s pharmacologistsGillman and Goodmanrecruited to investigatechemical warfare
  7. 7. First chemotherapy • Goodman and Gillman administerednitrogen mustard to mice with lymphoidtumors• In 1942, Gustav Lindskog (thoracicsurgeon) successfully treated a patientwith non-Hodgkin’s lymphoma withnitrogen mustard
  8. 8. Sidney FarberIn 1948, gave aminopterin(folate antagonist) leadingto first remission in a pediatricpatient with ALL
  9. 9. Combination chemotherapyFrei, Holland, and Freireichhypothesized strategy forcombination chemotherapybased on treatment of TBwith multiple drugs todevelop therapy in ALL
  10. 10. MOPP for lymphomaCanellos and DeVita – MOPP which cured patients withHodgkin and non-Hodgkin lymphoma
  11. 11. Chemotherapy drugsChemotherapy drugsChemotherapy drugs kill dividing cells
  12. 12. Side effects of chemotherapy• Kills the body’s normal rapidly dividingcells:– Bone marrow (myelosuppression)– Digestive tract (mucositis)– Hair follicles (alopecia)
  13. 13. Common classes of chemotherapyin lymphoma• Alkylators (cytoxan)• Anthracyclines(adriamycin)• Anti-metabolites(fludarabine)• Vinca alkaloids(vincristine, vinblastine)
  14. 14. Radiation
  15. 15. Discovery of X-rayWilhelm Röentgen1895
  16. 16. Marie CurieLate 1800’sdiscovered poloniumand radium and ledfirst studies of radiationto treat cancer
  17. 17. External beam radiotherapy(XRT)Currently delivered via linear acceleratorsCauses cellular DNA damageUse imaging to plan delivery of dose whilesparing normal tissuesGiven over days (fractionation) to allow forrecovery of normal cellsMany lymphomas very sensitive to XRTallowing use of lower doses than in solidtumors
  18. 18. Involved Field Radiation
  19. 19. Antibodies,Kinase inhibitorsNewer therapies
  20. 20. B-cellB-cellCD20 CD20CD20Punch holesDirect killingHow does rituximab work?Recruit immunecells
  21. 21. Brentuximab VedotinDrug (MMAE)Anti-CD30 antibodyBinds to CD30MMAE disruptsmicrotubule networkInternalized and goesto lysosomeMMAE is releasedCD-30
  22. 22. Diffuse large B-cell lymphoma• CHOP (cytoxan, adriamycin, vincristine,prednisone) standard treatment since1970’s• More aggressive regimens developed• More toxic• No more effective• RCHOP superior to CHOP
  23. 23. Indolent lymphomas• Early stage disease – radiation• Advanced stage disease:• Observation• Rituximab• Rituximab plus chemotherapy• Clinical trials
  24. 24. Chronic lymphocytic leukemia• Observation• Rituximab plus fludarabine with or withoutcyclophosphamide• Chlorambucil with or without rituximab• Rituximab plus bendamustine• Clinical trials
  25. 25. Hodgkin lymphoma - chemotherapy• ABVD (adriamycin, bleomycin, vinblastine,dacarbazine)• Generally well tolerated• Typically no infertility• Does not effect stem cells• Brentuximab vedotin - relapsed setting withon-going studies upfront
  26. 26. Hodgkin lymphoma - RT• Used as part of therapy for early stagedisease in some patients• Used for bulky areas in advanced disease
  27. 27. Novel pathways in NHL
  28. 28. What is a clinical trial?• Test the safety and how well a new drugworks in a particular disease• Test the safety and how well anestablished drug works in a new disease• Compare a new medication to standardtreatment• Goal for FDA approval of a drug for aparticular use
  29. 29. Clinical trials
  30. 30. Phase III clinical trialIn cancer studies, typically noplacebo except in certaincircumstances
  31. 31. Oversight clinical trials• Studies may be conducted by pharmaceuticalcompanies, single or group of investigators(including cooperative groups)• Careful oversight to ensure ethical and safeconduct• Institutional Review Board (IRB)– Evaluate protocol– Review consent form– Oversee ongoing conduct of trial
  32. 32. Summary• We’ve come a long way since nitrogenmustard• Combination chemotherapy remains part ofmany lymphoma regimens• Radiation is also an important modality forlymphoma• Rituximab has been a critical addition totreatment in NHL• New targeted therapies are under activeinvestigation

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