Negative)2.482 (1.003C6.140)0.0491.814 (0.621C5.299)0.276?Line of bortezomib (1st collection vs. above 0.05. All data were analyzed using the Statistical Package for the Sociable Sciences software (IBM? SPSS? Statistics, version 22.0 Chicago IL). ideals of 0.05 were considered statistically significant. Results Patient characteristics The baseline patient characteristics of the 565 individuals are demonstrated in Table?1. The median age was 63?years (18C92?years), and there were 309 males (54.7%). The proportion of individuals at International Rabbit polyclonal to DYKDDDDK Tag Staging System (ISS) stage III was 32.4%, while those at Revised International Staging System (R\ISS) stage III was 50.1%. Among the enrolled individuals, 42.7% underwent autoSCT. For those undergoing autoSCT, the most common induction therapy used was thalidomide centered (128/241, 53.1%), followed by cytotoxic chemotherapy based (77/241, 32.9%). Bortezomib\centered induction was used in 46 individuals (19.1%), and none received lenalidomide while induction for autoSCT (Table?1 and Fig.?1). All the individuals receiving standard chemotherapy as 1st\collection treatment were consequently exposed to either proteasome inhibitors and/or IMiDs in subsequent treatments. Table 1 Baseline characteristics of 565 enrolled individuals (%) /th /thead Age?Median (years, range)63 (18C92)? 65?years317 (56.1)?65?years248 (43.9)Sex?Male309 (54.7)Performance status?ECOG 0C1307 (54.4)?ECOG 2252 (44.6)?Missing6 (1.0)Ig type?IgG / A / Others276 (48.8) / 102 (18.1) / 23 (4.0)?Light chain164 (29.0)Light chain?Kappa / Lambda304 (53.8) / 261 (46.2)?Missing0ISS?I/II/III155 (27.5) /190 (33.6) /183 (32.4)?Missing37 (6.5)R\ISS?I/II/III39 (6.9) / 251 (38.1) / 283 (50.1)?Missing28 (5.0)Azotemia at MM analysis?Creatinine 2?mg/dL104 (18.4)?Creatinine 2?mg/dL461 (81.6)Treatment?autoSCT241 (42.7)?Thalidomide exposure322 (57.0)?Bortezomib exposure398 (70.4)1st line150Second line and beyond248?Lenalidomide exposure145 (25.7)1st line8Second line24Third line and beyond113 Open in a separate window ECOG, Eastern Cooperative Oncology Group; DSS, DurieCSalmon staging; ISS, International Staging System; R\ISS, Revised International Staging System; MM, multiple myeloma; SD, standard deviation; autoSCT, autologous stem cell transplantation. Standard cytogenetics and FISH abnormalities The rate of recurrence of each FISH panel used assorted (Table?2). IgH rearrangement was tested most often (520/565, 92.0%) and em t /em (14;16) least often (326/565, 57.7%). Overall, there were 277 (49.0%) individuals with all seven FISH panels. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), em t /em (14;16) in 2.5% (8/326), em t /em (4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), trisomy 1q21 in 40.8% (211/517), and del(9p21) in 2.2% (11/505) of instances. Table 2 FISH abnormalities thead valign=”top” th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ /th th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ Tested /th th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ Positive (%) /th th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ Alone (%) /th th align=”remaining” colspan=”3″ style=”border-bottom:solid 1px #000000″ valign=”top” rowspan=”1″ Combination (%) /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Two /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Three /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Four or more /th /thead del(17p13)33129 (8.8)7 (24.1)3 (10.3)4 (13.8)15 (51.7)del(13q14)519184 (35.5)19 (10.3)59 (32.1)72 (39.1)34 (18.5) em t /em (14;16)3268 (2.5)1 (12.5)1 (12.5)2 (25.0)4 (50.0) em t /em AG-17 (4;14)390109 (27.9)63 (25.4)2 (1.8)19 (17.4)25 (23.0)IgH rearrange520248 (47.7)68 (27.4)66 (26.6)79 (31.9)35 (14.1)+1q21517211 (40.8)42 (19.9)66 (31.3)70 (33.2)33 (15.6)del(9p21)50511 (2.2)5 (45.5)1 (9.1)3 (27.3)2 (18.2) Open in a separate windowpane FISH, fluorescence in situ hybridization; IgH rearrange, IgH rearrangement. FISH abnormalities and treatment response Table?3 and Number?2 represent treatment response to bortezomib and lenalidomide, regardless of treatment timing, according to different FISH status. The presence of del(17p13) seemed to decrease bortezomib response (Table?3), but the difference did not reach statistical significance. However, the presence of del(17p13) was associated with shorter PFS to bortezomib (median PFS 27?weeks for del(17p13)\negative group versus 9?weeks for del(17p13)\positive group, em P? /em = em ? /em 0.011) (Fig.?2A). Lenalidomide response was not altered relating to del(17p13) status. The presence of del(17p13) was associated with shorter PFS to autoSCT (median PFS 28?weeks for del(17p13)\negative group vs. 11?weeks for del(17p13)\positive group, em P? /em = em ? /em 0.024). Open in a separate window Number 2 Progression\free survival (PFS) after bortezomib, lenalidomide treatment, and autologous stem cell transplantation (autoSCT) relating to different FISH abnormalities. (A) PFS relating to del(17p13) status; (B) PFS relating to del(13q14) status; (C) PFS relating to em t /em (14;16) status; (D) PFS relating to em t /em (4;14) status; (E) PFS relating to IgH rearrangement status; (F) PFS relating to trisomy 1q21 status; (G) PFS relating to del(9p21) status. Table 3 Response rates to bortezomib and lenalidomide relating to FISH thead valign=”top” th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ /th th align=”remaining” colspan=”5″ style=”border-bottom:solid 1px #000000″ valign=”top” rowspan=”1″ Bortezomib /th th align=”remaining” colspan=”5″ style=”border-bottom:solid 1px #000000″ valign=”top” rowspan=”1″ Lenalidomide /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ CR /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ VGPR /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ PR /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ SD/PD /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ em P /em a /th th align=”remaining”.This, as mentioned before, allowed for nonbiased assessment of lenalidomide efficacy in a rather homogeneous establishing. using a Student’s value below 0.10 were considered and sequentially removed if the value in the multiple models was above 0.05. All data were analyzed using the Statistical Package for the Sociable Sciences software (IBM? SPSS? Statistics, version 22.0 Chicago IL). ideals of 0.05 were considered statistically significant. Results Patient characteristics The baseline patient characteristics of the 565 individuals are demonstrated in Table?1. The median age was 63?years AG-17 (18C92?years), and there were 309 males (54.7%). The proportion of individuals at International Staging System (ISS) stage III was 32.4%, while those at Revised International Staging System (R\ISS) stage III was 50.1%. Among the enrolled individuals, 42.7% underwent autoSCT. For those undergoing autoSCT, the most common induction therapy used was thalidomide centered (128/241, 53.1%), followed by cytotoxic chemotherapy based (77/241, 32.9%). Bortezomib\centered induction was used in 46 individuals (19.1%), and none received lenalidomide while induction for autoSCT (Table?1 and Fig.?1). All the individuals receiving standard chemotherapy as 1st\collection treatment were consequently exposed to either proteasome inhibitors and/or IMiDs in subsequent treatments. Table 1 Baseline characteristics of 565 enrolled individuals (%) /th /thead Age?Median (years, range)63 (18C92)? 65?years317 (56.1)?65?years248 (43.9)Sex?Male309 (54.7)Performance status?ECOG 0C1307 (54.4)?ECOG 2252 (44.6)?Missing6 (1.0)Ig type?IgG / A / Others276 (48.8) / 102 (18.1) / 23 (4.0)?Light chain164 (29.0)Light chain?Kappa / Lambda304 (53.8) / 261 (46.2)?Missing0ISS?I/II/III155 (27.5) /190 (33.6) /183 (32.4)?Missing37 (6.5)R\ISS?I/II/III39 (6.9) / 251 (38.1) / 283 (50.1)?Missing28 (5.0)Azotemia at MM analysis?Creatinine 2?mg/dL104 (18.4)?Creatinine 2?mg/dL461 (81.6)Treatment?autoSCT241 (42.7)?Thalidomide exposure322 (57.0)?Bortezomib exposure398 (70.4)1st line150Second line and beyond248?Lenalidomide exposure145 (25.7)1st line8Second line24Third line and beyond113 Open in a separate window ECOG, Eastern Cooperative Oncology Group; DSS, DurieCSalmon staging; ISS, International Staging System; R\ISS, Revised International Staging System; MM, multiple myeloma; SD, standard deviation; autoSCT, autologous stem cell transplantation. Standard cytogenetics and FISH abnormalities The rate of recurrence of each FISH panel used assorted (Table?2). IgH rearrangement was tested most often (520/565, 92.0%) and em t /em (14;16) least often (326/565, 57.7%). Overall, there were 277 (49.0%) individuals with all seven FISH panels. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), em t /em (14;16) in 2.5% (8/326), em t /em (4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), trisomy 1q21 in 40.8% (211/517), and del(9p21) in 2.2% (11/505) of instances. Table 2 FISH abnormalities thead valign=”top” th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ /th th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ Tested /th th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ Positive (%) /th th align=”remaining” rowspan=”2″ valign=”top” colspan=”1″ Alone (%) /th th align=”remaining” colspan=”3″ style=”border-bottom:solid 1px #000000″ valign=”top” rowspan=”1″ Combination (%) /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Two /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Three /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Four or more /th /thead del(17p13)33129 (8.8)7 (24.1)3 (10.3)4 (13.8)15 (51.7)del(13q14)519184 (35.5)19 (10.3)59 (32.1)72 (39.1)34 (18.5) em t /em (14;16)3268 (2.5)1 (12.5)1 (12.5)2 (25.0)4 (50.0) em t /em (4;14)390109 (27.9)63 (25.4)2 (1.8)19 (17.4)25 (23.0)IgH rearrange520248 (47.7)68 (27.4)66 (26.6)79 (31.9)35 (14.1)+1q21517211 (40.8)42 (19.9)66 (31.3)70 (33.2)33 (15.6)del(9p21)50511 (2.2)5 (45.5)1 (9.1)3 (27.3)2 (18.2) Open in a separate windowpane FISH, fluorescence in situ hybridization; IgH rearrange, IgH rearrangement. FISH abnormalities and treatment response Table?3 and Number?2 represent treatment response to bortezomib and lenalidomide, no matter treatment timing, according to different FISH status. The presence of del(17p13) seemed to decrease bortezomib response (Table?3), but the difference did not reach statistical significance. However, the presence of del(17p13) was associated with shorter PFS to bortezomib (median PFS 27?weeks for del(17p13)\negative group versus 9?weeks for del(17p13)\positive group, em P? /em = em ? /em 0.011) (Fig.?2A). Lenalidomide AG-17 response was not altered relating to del(17p13) status. The presence of del(17p13) was associated with shorter PFS to autoSCT (median PFS 28?weeks for del(17p13)\negative group vs. 11?weeks for del(17p13)\positive group, em P? /em = em ? /em 0.024). Open in a separate window Number 2 Development\free success (PFS) after bortezomib, lenalidomide treatment, and autologous stem cell transplantation (autoSCT) regarding to different Seafood abnormalities. (A) PFS regarding to del(17p13) position; (B) PFS regarding to del(13q14) position; (C) PFS regarding to em t /em (14;16) position; (D) PFS regarding to em t /em (4;14) position; (E) PFS regarding to IgH rearrangement position; (F) PFS regarding to trisomy 1q21 position; (G) PFS regarding to del(9p21) position. Desk 3 Response prices to bortezomib and lenalidomide regarding to Seafood thead valign=”best” th align=”still left” rowspan=”2″ valign=”best” colspan=”1″ /th th align=”still left” colspan=”5″ design=”border-bottom:solid 1px #000000″ valign=”best” rowspan=”1″ Bortezomib /th th align=”still left” colspan=”5″ design=”border-bottom:solid 1px #000000″ valign=”best” rowspan=”1″ Lenalidomide /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ CR /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ VGPR /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ PR /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ SD/PD /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ em P /em a /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ CR /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ VGPR /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ PR /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ SD/PD /th th align=”still left” valign=”best” rowspan=”1″ colspan=”1″ em P /em a /th /thead del(17p13)?Absence43 (20.2)47 (22.1)76 (35.7)34 (15.9)0.0925 (7.0)5 (7.0)33 (45.5)25 (35.3)1.000?Existence2 (8.3)4 (16.4)9 (37.5)5 (20.9)1 (11.1)05 (55.6)3 (33.3)del(13q14)?Absence44 (18.9)50 (21.5)87 (37.3)41 (17.6)0.9165 (7.2)8 (11.6)34 (49.3)22 (31.9)0.002?Presence30 (22.1)34 (25.0)41 (30.1)24 (17.7)4 (7.7)2 (3.8)15 (28.8)28 (53.9) em t /em (14;16)?Absence45 (20.0)50 (22.2)79 (35.1)35 (15.6)0.6606 (7.9)4 (5.3)37 (48.7)26 (34.2)0.379?Existence005 (71.4)2 (28.6)01.