Rituximab, Cyclophosphamide, Dexamethasone (RCD) regimen induces cure in WSU-WM xenograft model and a partial remission in previously treated Waldenstrom's macroglobulinemia patient.
Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the antitumor effects of Rituximab (RTX), Cyclophosphamide (CTX), Dexamethasone (DEX) [RCD]-Regimen in vivo WSU-WM SCID xenograft and in a patient with WM. For the pre-clinical efficacy study, WSU-WM-bearing SCID mice were randomly assigned to receive RTX (150 mg/kg/inj, i.v., QDX5), CTX (90 mg/kg/inj, s.c. QDX5) as single agents or diluent. The combination group received RTX at 150 mg/kg/inj, QDX5; CTX at 150 mg/kg/inj, QODX3 and DEX at 1.0 mg/kg/inj, i.v., QDX5. Tumor growth inhibition (T/C), tumor growth delay (T - C), and log10 kill (net) for RTX and CTX were 24.5%, 37 days, 5.52 and 88%, 0.0 days, 0.0log10 kill, respectively. No cures were observed with either agent; however, all mice (6/6, with bilateral tumors) were cured when treated with RCD-regimen. A 57-year-old patient with relapsed WM was treated with the RCD-regimen and showed an excellent partial remission for seven months. The patient tolerated the treatment very well, the hemoglobin improved dramatically, platelets remained stable, the IgM level normalized and there was only minimal involvement of bone marrow. Based on these results, the RCD regimen is effective against WM and its activity should be further evaluated in clinical trials.
Mohammad
Ramzi M
RM
Department of Internal Medicine, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI 48201, USA. mohammad@karmanos.org
Aboukameel
Amro
A
Nabha
Sanaa
S
Ibrahim
Dina
D
Al-Katib
Ayad
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003907:Dexamethasone; D003520:Cyclophosphamide