Tamoxifen/methotrexate (TAM/MTX) induces meaningful responses in multiple myeloma (MM) patients (PTS) failing auto transplant (TX)

A. Passas, A. Rapoport, J. Bolanos-Meade, C. Shanholtz, M. Cottier-Fox, G. Tricot

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Based on data showing antiestrogen-induced apoptosis of MM cell lines (Treon et al, 1998), we designed a study using tamoxifen-based treatment in pts with relapsing or refractory MM. Methotrexate was added because of its anti-angiogenesis effect and the possible downregulation of IL-6. MM pts were conditioned with melphalan and BCNU. Post-Tx chemotherapy (PTC) was started 3 months (mo.) PT and given q 3mo.x4 or until relapse. The PTC consisted of Cytoxan, Dexamethasone (DEX), Etoposide, Cisplatin (CDEP) alternating with DEX. Taxol, Cisplatin. Between 10/98-10/99, we enrolled 11 consecutive MM pts with either relapsing (10) or refractory (1) disease PT. One additional pt who had failed conventional chemotherapy, but was ineligible for Tx, was also enrolled. There were 7 males and 5 females, (median age: 57 y), with IgG MM (6), nonsecretory (NS) disease (3), IgA (2) and light chain MM(1). Response to Tx included partial response (PR) (6 pts) and stable and progressive disease (2 pts each). All pts had relapsed 2.5-21 mo. PT. 5 while still on PTC. 8 pts had high-risk cytogenetic abnormalities at relapse [any translocation (#7) or del 13(# 1 )]. Plasmablastic features and extramedullary disease occurred in 1 pt each. All pts started Tam 20 mg P.O. bid and Mix 15 mg P.O. twice weekly. DEX pulse was added, for 1 course, in 2 pts who were pancytopenic. Tam dose was doubled at 4-week intervals if no response or toxicity were seen. The treatment (Rx) was well tolerated. One pt (on Tam 160 mg bid and fluconazole) developed tremors, which subsided with dose reduction. Objective responses were seen in 4 pts, all males. 2 pts achieved CR. Both had NS MM. The first pt [relapsed 8 mo. PT with pancytopenia, plasmablastic picture and t (11;19)] remained in CR for 8 mo. with normal CBC and karyotype. This pt had also received one course of pulse DEX at the initiation of Rx. He later relapsed and died of fungal infection after MUD BMT. The second pt [relapsed on PT d+70 with thrombocytopenia, anemia and packed BM by MM] has been in continuous CR for 18 mo. with normal BM, CBC and normalization of immunoglobulins. Both pts responded to the starting dose of Tam (20 mg bid) and had platelet (pit) recovery within 6-8 weeks. Two pts achieved stable disease. The first pt [IgG MM, relapsed 18 mo. PT with slowly rising "M" levels] has been on Tam/Mtx for 10 mo. However, given the slow pace of his MM, no definitive conclusion on the effect ot Tam/Mtx can be made. The second pt [NS MM, relapsed 12 mo. PT with decreasing pit count, increasing BM plasmacytosis and complex karyotype] received Tam/Mtx for 6 mo. with stabilization of his pit count but without effect on the abnormal karyotype. He later relapsed and achieved PR with thalidomide (Thai). Two additional pts were switched to Thai when no response was seen after 12 weeks of Rx. One of these pts had increasing "M" levels (while on Thai) which stabilized after the reintroduction of Tam. 6 pts died of progressive MM at 4-10 weeks after initiation of Rx. In conclusion Tam/Mtx induced meaningful responses without toxicity in at least 2/12 MM pts with very unfavorable features, such as poor or short response to Tx and high-risk cytogenetics. Further studies on the mechanisms of action and possible synergy with Thalidomide and/or cytotoxic agents are warranted.

Original languageEnglish (US)
Pages (from-to)286b-287b
Issue number11 PART II
StatePublished - Dec 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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