Sequential, cycling maintenance therapy for post transplant multiple myeloma.
High-dose chemotherapy with autologous stem cell transplantation in patients with newly diagnosed multiple myeloma can prolong survival but is not curative. Maintenance therapy post transplant may prolong the disease-free interval and impact overall survival. We have conducted a phase II pilot study of 28 post transplant myeloma patients treated with a sequential, cycling maintenance regimen. The regimen was designed to include a variety of active myeloma agents chosen for ease of administration to enhance patient compliance and scheduled sequentially to minimize toxicity. The 12-month cycling schedule included dexamethasone (months 1-3); melphalan and prednisone (months 4, 5); cyclophosphamide and prednisone (months 6, 7); alpha-interferon (months 8-10); followed by a drug holiday (months 11, 12). The regimen was generally well tolerated with five patients developing reversible grade III-IV toxicity (diabetes-induced hyperglycemia in four, neutropenia in one). There was one toxic death on study due to non-neutropenic pneumonia and sepsis. Median event-free survival from transplant was 36.9 months (95% CI 23.6 - upper limit not yet reached) with median overall survival not yet reached at a median follow-up of 44 months. This concept of cycling, sequential maintenance with various agents, perhaps including newer biological, targeted agents, warrants further investigation in multiple myeloma.
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Department of Haematology/Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada. Christine.Chen@uhn.on.ca
Nanji
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Prabhu
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Beheshti
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Sutton
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D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous
D000893:Anti-Inflammatory Agents; D018906:Antineoplastic Agents, Alkylating; D016898:Interferon-alpha; D003907:Dexamethasone; D003520:Cyclophosphamide; D008558:Melphalan; D011241:Prednisone