Familial disease predisposition impacts treatment outcome in patients with Waldenström macroglobulinemia.
Familial disease is common in Waldenström macroglobulinemia (WM). We examined the impact of familial disease status on treatment outcome in WM and observed that familial disease was associated with inferior outcomes. However patients with familial WM receiving a bortezomib-containing regimen showed improved treatment outcomes vs. those receiving non–bortezomib-containing regimens. Bortezomib-containing regimens may therefore represent a more optimal treatment approach for patients with familial WM.


BACKGROUND
We examined the impact of familial predisposition on treatment outcome in 135 patients with Waldenström macroglobulinemia (WM), 26.7% of whom had first- or second-degree relatives with a B-cell lymphoproliferative disorder.


METHODS
All patients were rituximab naive and received a rituximab-containing regimen. There were no significant differences in baseline characteristics between cohorts.


RESULTS
Overall response (93.9% vs. 75.0%; P = .029) and complete response/very good partial response (CR/VGPR) (23.2% vs. 16.7%; P < .0001), time to progression (TTP) (45.5 vs. 21 months; P = .015) and time to next therapy (TTNT) (50.0 vs. 33.0 months; P = .024) favored patients with sporadic WM. By multivariate analysis, familial predisposition was an independent marker for disease progression (hazard ratio, 0.554). Patients with familial but not sporadic disease exhibited better responses, including CR/VGPR attainment (P = .0006) and a trend for longer progression-free survival (> 33 vs. 20.6 months; P = .08), with bortezomib-containing therapy.


CONCLUSIONS
The findings convey that familial predisposition is an important determinant of treatment outcome in WM. Prospective studies to confirm these observations are needed.
Bing Center for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
Steven P
SP
Treon
Christina
C
Tripsas
Christina
C
Hanzis
Leukothea
L
Ioakimidis
Christopher J
CJ
Patterson
Robert J
RJ
Manning
Patricia
P
Sheehy
Barry
B
Turnbull
Zachary R
ZR
Hunter
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000235:genetics*
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine