TABLE 2.
Studies with Treatment-Naïve WM patients
| Study | Regimen | No. of Pt | Med. Age (range) | Risk group | Treatment response (%) | Survival rates | Med F/U (mo) |
|---|---|---|---|---|---|---|---|
| Dimopoulos8⊖ 2002 |
R: 375mg/m2/weekly IV infusion total 4 consecutive weeks, repeat 4 weeks courses of R in patients without disease progression at 3 months | 27 | 72 (39–85) |
NR | PR 12 (44) MRR 44% ORR 44% |
PFS 33.3% | 15.7 |
| Gertz9 2004 |
R: 375mg/m2/weekly IV infusion total 4 consecutive weeks | 34 | 66.4 (44.8–81.4) |
NR | MR 6 (18) MRR 0% ORR 18% |
PFS NR OS 97.1% |
NR |
| Dimopoulos10 2002 |
Extended R: 375mg/m2/weekly IV total 8 cycles at weeks 1–4 and 12–16 (if no disease progression) | 17 | 74 (39–84) |
NR | PR 6 (35) MRR 35% ORR 35% |
PFS 41.2% OS 94.1% |
16–40 |
| Treon11‡ 2005 |
Extended R: 375mg/m2/weekly IV total 8 cycles at weeks 1–4 and 12–16 | 29 | 65 (43–90) |
NR | PR 14 (48) MR 5 (17) MRR 48% ORR 65% |
PFS 89.5% OS NR |
29 |
| Furman12
P 2011 |
Ofatumumab: 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) |
NR | PR 13 (35) MR 9 (24) ORR 66.7%£ |
NR | NR |
| Ghobrial13 2011 |
Bortezomib + R: Bortezomib 1.6mg/m2 on days 1, 8, 15 every 28 days total 6 cycles with R 375mg/m2/weekly IV infusion on cycles 1 and 4 | 26 | 62.5 (43–85) |
High 3(12) Int 11 (42) Low 10 (38) NA 2 (8) | CR 2 (8) PR 15 (58) MR 9 (35) MRR 65% ORR 100% |
1yr PFS 75% 1yr OS 96% |
14 |
| Treon14 2009 |
BDR: B 1.3mg/m2 IV, D 40mg on day 1,4, 8, 11, and R 375mg/m2 on day 11,4 consecutive cycles for induction, then 4 cycles, each 3 months apart, for maintenance therapy | 23 | 66 (48–86) |
NR | CR 3 (13)/nCR 2 (9) VGPR 3 (13)/PR 11 (48) MR 3 (13) MRR 83% ORR 96% |
PFS 78.3% OS 100% |
22.8 |
| Dimopoulos15 2013 |
BDR: B 1.3mg/m2 IV on days 1,4, 8 and 11 followed by weekly B 1.6mg/m2 IV on days 1, 8, 15, and 22 every 35 days for 4 cycles, followed by D 40mg and R IV 375mg/m2 in cycle 2 and 5 | 60 | 70 (40–83) |
Low 27 (45) † Int 24 (40) High 9(15) | CR 2 (3) VGPR 4 (7)/PR 38 (65) MR 10 (17) MRR 40 (73) ORR 54 (90) |
3yr PFS 41% 3yr OS 82% |
42 |
| Treon16 2014 |
KRD: carfilzomib 20mg/m2 IV for 1st cycle, then 36mg/m2 for 2nd cycle and beyond) + R 375mg/m2 on days 2 and 9 every 3 weeks for 6 cycles + D 20mg IV on days 1,2, 8, and 9 | 31 | 61 (47–75) |
Low 11 (36) Int 15 (48) High 5(16) | CR 1 (3) VGPR 10 (32) PR 10 (32) MR 6 (19) MRR 67.7% ORR 87.1% |
PFS 64.5% OS 100% |
15.4 |
| Treon16 2014 |
KRD: carfilzomib 20mg/m2 IV (cycle 1), 36mg/m2 (cycle 2–6), D 20mg IV on days 1, 2, 8, and 9, R 375mg/m2 on days 2 and 9 every 21 days, followed by maintenance with C 36mg/m2 IV, D 20mg IV on days 1 and 2, R 375mg/m2 on day 2 every 8 weeks for 8 cycles. | 31 | 61 (47–75) |
Low 11 (36) † Int 15 (48) High 5(16) | CR 1 (4) VGPR 10 (36)/PR 10 (36) MR 6 (21) MRR 67.7% ORR 87.1% |
PFS 64.5% OS 100% |
15.4 |
| Dimopoulos17,18 2007 |
RCyD: D 20mg IV followed by R 375mg/m2 IV on day 1. Cy 100mg/m2 PO bid on days 1–5. Repeated treatment every 21 days for 6 cycles | 72 | 69 (33–89) |
NR | CR 5 (7) PR 48 (67) MR 6 (9) MRR 73.6% ORR 81.9% |
2yr PFS 67% 2yr OS 81% |
23.4 |
| Treon19€ 2009 |
R + Lenalidomide: 48 weeks of lenalidomide 25 mg/day PO for 3 weeks and then1week off along with R 375 mg/m2/wk IV dosed on weeks 2 to 5 and 13 to16 | 16 | 65 (49–85) |
NR | PR 4 (25) MR 4 (25) MRR 25% ORR 50% |
PFS 25% | 31.3 |
| Buske20 2009 |
CHOP: cyclophosphamide 750 mg/m2 IV, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 IV on day 1, prednisone 100 mg/m2 PO on days 1–5, every 3 weeks, total 4–8 cycles | 25 | 62 (37–74) |
NR | CR 1 (4) PR 14 (56) MRR 60% ORR 60% |
2yr PFS 47% | NR |
| R + CHOP: R 375 mg/m2/day on the day before the CHOP | 23 | 58 (40–78) |
NR | CR 2 (9) PR 19 (83) MRR 91.3% ORR 91.3% |
2yr PFS 78% | NR | |
| 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) |
NR | CR 2 (5) VGPR 14 (33)/PR 21(49) MR 4 (9) MMR 88.9%£ ORR 96.3%£ |
2yr PFS 67% | 40.3 |
| Tedeschi22 2012 |
R + Fludarabine + Cyclophosphamide: R 375 mg/m2 IV on day 1, fludarabine 25 mg/m2, cyclophosphamide 250 mg/m2 IV on days 2–4, every 28 days, total 6 cycles | 43 | 65 (36–77) |
Low 14 (33) Int 16 (38) High 12 (29) | CR 8 (19) VGPR 6 (14)/PR 19 (44) MR 1 (2) MRR 76.7% ORR 79.1% |
PFS NR 2yr OS 88.4% 4yr OS 69.1% |
38.8 |
| Souchet23Ω 2016 |
FCR: R 375mg/m2 IV on day 1, F 40 mg/m2 PO on days days 1–3, C 250 mg/m2 PO on days 1–3, every 4 weeks for total 6 course. | 82 | 61 (NR) |
NR | VGPR 10 (40)/PR 9 (36) MR 3 (12) MRR 76%£ ORR 88%£ |
3yr PFS 96% 3yr OS 96% |
47 |
| Rummel24 2013 |
RB: B 90 mg/m2 on days 1–2 of a 4 week cycle + R 375 mg/m2 on day 1 of each cycle | 22λ | 64 (56–69) |
NR | NR | PFS HR 0.33 (95%CI 0.110–0.64) |
45 |
| R-CHOP: cyclophosphamide 750mg/m2, doxorubicin 50 mg/m2, vincristine 1.4mg/m2 (up to dose of 2mg) on day 1, and prednisone 100mg on days 1–5, every 3 weeks + R 375mg/m2 on day 1 of each cycle | 19λ | NR | NR | 45 | |||
| Tripsas25 2013 |
Everolimus: 10mg daily until progression or unacceptable toxicity | 33 | 62 (41–80) |
NR | VGPR 2 (6)/PR 18 (55) MR 4 (12) MRR 60.6% ORR 72.7% |
NR | 9 |
Risk stratification by International Prognostic Scoring System for WM (ISSWM);
A total of 15 patients (56%) had no prior therapy;
A total of 21 patients (41%) had no prior therapy;
A total of 23 patients (82%) had previous treatment;
A total of 9 patients (24%) had no prior therapy;
A total of 4 patients (25%) had previous treatment;
A total of 27 (63%) had no prior therapy;
A total of 25 (30%) had no prior therapy;
This study included total 514 patients with indolent lymphoma (follicular lymphoma (n=279), marginal zone lymphoma (n=67), WM (n=41), SLL (n=21), unclassified (n=12)) and mantle cell lymphoma (n=94);
Values with treatment native patients only;
Defined as at least 25% increase from the baseline.
Abbreviation: BDR (bortezomib, dexamethasone, rituximab), KRD (dexamethasone, rituximab, carfilzomib), RCyD (rituximab, cyclophosphamide, dexamethasone), BR (rituximab, bendamustine), FCR (fludarabine, cyclophosphamide, rituximab), MRR (major response rate), CR (complete response), nCR (near CR), 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), CI (confidence interval), Tx (therapy), PFS (progression free survival), OS (overall survival), Mo (months).