Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials.
OBJECTIVE
Four Southwest Oncology Group (SWOG) standard-dose chemotherapy protocols for multiple myeloma (MM) initiated between 1982 and 1992 were evaluated. The purpose was to clarify the predictive value of specific levels of myeloma-associated monoclonal protein reduction and time to first progression using mature data sets.


METHODS
Study data on 1,555 eligible previously untreated patients with MM enrolled onto SWOG phase III trials 8229, 8624, 9028, and 9210 were used in these analyses. Six-month and 12-month landmark analyses were performed to evaluate the outcome for patients in each response category.


RESULTS
The overall and event-free survivals for the four protocols combined were 33 months and 18 months, respectively. Using 6- and 12-month landmarks, the median survivals of 30 to 35 months were not different for responders (> or = 50% and > or = 75% regression) versus nonresponders in patients without disease progression before the landmarks. Conversely, at the 6- and 12-month landmarks, the median survivals for patients who had experienced disease progression were 13 and 15 months, respectively, versus a 34-month median for patients who did not experience progression. Using the Cox survival model, with response and progression considered as time-dependent covariates, survival duration was influenced more by the occurrence of progression than by the occurrence of response.


CONCLUSIONS
The magnitude of response, as a single variable, does not predict survival duration. Patients with response and stable disease have equivalent outcome. Only patients with progressive disease have a poorer outcome. The best indicator of survival is time to first progression.
Durie
Brian G M
BG
Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. bdurie@salick.com
Jacobson
Joth
J
Barlogie
Bart
B
Crowley
John
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009194:Myeloma Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015206:Southwestern United States; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D009194:Myeloma Proteins