TABLE 3.
Studies of WM patients with Prior Therapy or Refractory/Relapsed Disease
| Study | Regimen | No. of Pt | Med. age (range) | Med No. of prior Tx (range or %) | Risk group | Treatment response (%) | Survival rates | Med F/U (mo) |
|---|---|---|---|---|---|---|---|---|
| Byrd26 1999 |
R: 375mg/m2/weekly IV infusion total 4 or 8 consecutive weeks | 7 | 60 (50–75) |
3 (1–4) |
NR | PR 3 (43) MRR 42.9% ORR 42.9% |
NR | NR |
| Treon27 2015 |
Ibrutinib: 420mg po daily | 63 | 63 (44–86) |
2 (1–9) |
Low 14 (22) Int 27 (43) High 22 (35) |
VGPR 10 (16) PR 36 (57) MR 11 (17) MRR 73.0% ORR 90.5% |
2yr PFS 69.1% 2yr OS 95.2% |
NR |
| Gertz9 2004 |
R: 375mg/m2/weekly IV infusion total 4 consecutive weeks | 35 | 70.3 (46.8–89.2) |
NR | NR | MR 11 (31) MRR 0% ORR 31.4% |
PFS NR OS 71.4% |
NR |
| Furman12
P 2011 |
Ofatumumab: 300mg for week 1 and 1000mg for weeks 2–4 (G1) or 2000mg for weeks 2–5 (G2). If stable disease or minimal response at 16th week, additional 300mg for week 1 and 2000mg for weeks 2–5 | 37 | 63 (43–85) |
3 (1–5) |
NR | PR 13 (35) MR 9 (24) ORR 57.1%£ |
NR | NR |
| Dimopoulos28 2005 |
Bortezomib: Bortezomib 1.3mg/m2 IV on days 1,4, 8 and 11 in a 21 day cycle, total 4 cycles | 10 | 78 (48–84) |
3 (1–4) |
NR | PR 6 (60) ORR 60% MRR 60% |
NR | NR |
| Treon29 2007 |
Bortezomib: Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, total 8 cycles | 27 | 62 (44–79) |
2 (0–3) |
NR | CR/PR 13 (48) MR 10 (37) ORR 48.1% MRR 85.2% |
PFS 26% | 18.2 |
| Ghobrial30 2010 |
Bortezomib + R: Bortezomib IV 1.6mg/m2 on days 1, 8, 15, every 28 days for 6 cycles, R 375mg/m2/weekly IV on cycle 1 and 4 | 37 | 64 (42–81) |
1: 11 (30) 2: 8 (22) 3: 7 (19) > 3: 11 (30) |
Low 6 (16) Int 11 (30) High 18 (49) NA 2 (5) |
CR 2 (5) PR 21 (57) MR 9 (24) ORR 62.2% MRR 86.5% |
1yr PFS 58% 1yr OS 94% |
16 |
| Treon31 2011 |
B + R or ofatumumab: B 90 mg/m2 IV on days 1, 2 total 6 cycles with R 375 mg/m2 IV on day 1 or 2 every 4 weeks or ofatumumab 1g IV on day 1 | 30 | 68 (44–84) |
2 (1–9) |
NR | VGPR 5 (17)/PR 20 (67) MRR 83.3% ORR 83.3% |
NR | 7.5 |
| Treon21¥ 2009 |
R + Fludarabine: R 375 mg/m2/week IV at weeks 1 to 4, 17, 18, and 30, 31 with 6 cycles of fludarabine 25 mg/m2 daily for 5 days at weeks 5, 9, 13, 19, 23, and 27 | 43 | 61 (52–75) |
0 (0–2) |
NR | CR 2 (5) VGPR 14 (33)/PR 21(49) MR 4 (9) MRR 81.3%£ ORR 93.8%£ |
2yr PFS 38% | 40.3 |
| Souchet23Ω 2016 |
R + Fludarabine + Cyclophosphamide: R 375mg/m2 IV on day 1, fludarabine 40 mg/m2 PO on days 1–3, cyclophosphamide 250 mg/m2 PO on days 1–3, every 4 weeks for total 6 course. | 82 | 61 (NR) |
1 (1–4) |
NR | CR 5 (9) VGPR 16 (37) PR 23 (40) MR 3 (5) ORR 77.2%£ MMR 82.4%£ |
3yr PFS 73% 3yr OS 89% |
47 |
| Ghobrial32,33 2014 |
Everolimus: 10mg daily | 50 | 63 (43–85) |
3 (1–11) |
Low 11 (50) Int 7 (32) High 4 (18) |
PR 21 (42) MR 14 (28) MRR 42% ORR 70% |
6mo PFS 75% 12mo PFS 62% |
11.5 |
| Ghobrial34 | Everolimus+Bortezomib+R (phase I): everolimus 5 or 10 mg with R at 375 mg/m2 or with R and bortezomib at 1.3 or 1.6 mg/m2 for the phase I. Everolimus+Bortezomib+R (phase II): Everolimus 10mg daily, bortezomib 1.6mg/m2 IV weekly on days 1, 8, 15 ever 28 days, and R IV 375mg/m2 weekly on days 1, 8 15, 22 every 28 days in cycle 1 and 4 only. |
46 | 64 (48–84) |
2 (1–9) |
Low 18 (39) Int 21 (46) High 7 (15) |
CR 2 (4) PR 21 (46) MR 17 (37) MRR 50% ORR 87% |
1yr PFS 65% 2yr PFS 42% |
15 |
A total of 5 patients (18%) had no prior treatment in this study;
A total of 27 (63%) had no prior therapy;
A total of 9 patients (24%) had no prior therapy;
A total of 25 patients had no prior treatment in this study;
Values with previously treated patients only.
Abbreviation: R (rituximab), B (bendamustine), MRR (major response rate), PPH (plasmapheresis), CR (complete response), PR (partial response), MR (minimal response), MRR (major response rate; defined as CR+VGPR+PR), ORR (overall response rate; defined as CR+VGPR+PR+MR), Int (intermediate), Pre (pre-treatment), Post (post-treatment), NR (not reported), Tx (therapy), PFS (progression free survival), OS (overall survival), MO (months).