MDR-1 expression and response to vincristine, doxorubicin, and dexamethasone chemotherapy in multiple myeloma refractory to alkylating agents.
OBJECTIVE
To assess whether the presence of enhanced multiple drug resistance (MDR)-1 gene expression in multiple myeloma (MM) patients predicts survival, as well as response to vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy.


METHODS
Sixty-three MM patients refractory to alkylating therapy were studied. The presence of the MDR-1 gene product, a 170-kd glycoprotein (P-170), was analyzed in bone marrow plasma cells by means of the alkaline phosphatase (APAAP) technique using the P-170-specific monoclonal antibody (MoAb) C219. The prognostic value of MDR-1 gene expression, examined before VAD treatment, was compared with other established prognostic factors including beta 2-microglobulin, albumin, lactate dehydrogenase (LDH), and the plasma cell labeling index.


RESULTS
Fifty-nine percent of all samples were P-170-positive. No association could be demonstrated between response to VAD and MDR-1 gene expression (chi 2 P = .359), in contrast to high serum beta 2-microglobulin levels, which were positively correlated with response (P = .006). P-170-positive and -negative patients showed a median survival duration of 23 and 22 months, respectively, a difference that was not statistically significant (P = .9). beta 2-microglobulin, LDH, albumin, and the plasma cell labeling index were all significantly correlated with survival.


CONCLUSIONS
These results indicate that other mechanisms of resistance must be involved in MM apart from MDR. The role of MDR status at this stage of disease may be biased by the major contribution of dexamethasone to induction of response by VAD in MM patients.
Cornelissen
J J
JJ
Department of Haematology, University Hospital Utrecht, The Netherlands.
Sonneveld
P
P
Schoester
M
M
Raaijmakers
H G
HG
Nieuwenhuis
H K
HK
Dekker
A W
AW
Lokhorst
H M
HM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000477:Alkylating Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000032:analysis*; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004351:Drug Resistance; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000477:Alkylating Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin