Targeted Therapy in Hematology

Dieter Hoelzer – Frankfurt am Main

Christoph Zielinski – Vienna, Austria

Hans-Joachim Schmoll – Halle, Germany

Richard Greil – Salzburg, Austria

“Magic bullets” in Hematology

• Rituximab (Mab Thera) in B-cell NHL

• Imatinib (Gleevec) in CML

• Thalidomide in multiple myeloma

• Bortezomib (Velcade) in multiple myeloma

Rituximab in Non-Hodgkin’s Lymphoma (1)

• Indications– Follicular lymphoma first line + CT (CVP)– Follicular lymphoma in third line– Diffuse B cell large cell lymphoma in

combination with conventional chemotherapy

• Treatment– 375 mg/m², i.v. – weekly as single agent– Three weekly with chemotherapy– Infusion reaction

Rituximab in Non-Hodgkin’s Lymphoma (2)

Questions

• Other indications for rituximab?

• Is Id vaccination following chemotherapy superior to passive treatment with anti-CD20 mAb following chemotherapy?

• Role of radioimmunotherapy for NHL?

• New antibodies targeting CD20 any better?

• Other targets in case of resistance against rituximab?

Imatinib (Gleevec) in CML (1)

• Indication

Philadelphia chromosome (Ph) positive CML in first line

hematologic, cytogenetic and molecular response

• Treatment– Orally, 400-800 mg/day– GI complaints, muscle cramps, superficial edema,

leucopenia, neutropenia

Imatinib (Gleevec) in CML (2)

Questions

• Second generation of targeted therapic

long-term safety?

• What to do with AMN107 and BMS-354825 resistant mutants?

• Combination of drugs any future?

Thalidomide in Multiple Myeloma (1)

• IndicationEarly relapse after 1st and 2nd line therapy or chemotherapy-refractory disease

• TreatmentOrally, 50-400 mgTeratogenicFatigue – sleepy – constipation, skin rashPolyneuropathy: sometimes irreversibleDVT: 1-3%

Thalidomide in Multiple Myeloma (2)

Questions

• Thalidomide plus dexamethasone standard?

• Role of lenalidomide (+ dexamethasone)?

• Long-term outcome?

Bortezomib (Velcade) in MM (1)

• IndicationMM patients, who have received at least 2 prior treatment regimens, showing PD

• Treatment– 1.3 mg/m² i.v. push– One cycle: 2 x/week during 2 weeks, then 10 days

rest– GI symptomes, tiredness, neuropathy (30%)

cytopenia/thrombocytopenia (30%) orthostatic hypotension

Bortezomib (Velcade) in MM (2)

Questions

• Can it be used in combination with lenalidomide and lower doses of dexamethasone in order to enhance cytotoxicity end decrease toxicity?

• Where should bortezomib be positioned?