Re-Treatment with Rituximab in ITP: Comparison of Standard Dose with 2 Forms of Augmented Rituximab.

The purpose of this study was to investigate treatment (tmt) with Rituximab ® in patients (pts) with ITP who had previously received R. Re-treatment (re-tmt) was administered either at standard (std) dose (375 mg/m2 x 4) n=15 or as augmented R, n= 14 (below). Eligibility criteria included primary chronic ITP, platelet count (plt ct)< 30K x 2 within a month, age > 12 years, and prior receipt of std dose R. Augmented R pts were randomised to receive either R-CVP (group A,n=7) or Double Dose R (DDR) (group B,n=7). Group A pts received 1 dose of std dose R 1st and then 3 doses of R-CVP consisting of R, IV doses of Cyclophosphamide 750 mg/m2 & vincristine 1.4 mg/m2 (max 2 mg) and 100 mg prednisone PO daily for 5 days at 3 week intervals. Group B pts were treated with R 750 mg/m2/dose IV weekly for 4 weeks. Pts could receive IVIG during the initial tmt period. Two heavily pre-treated pts did not tolerate R-CVP well and refused the 3rd cycle; 1 std dose pt had an allergic reaction and could not complete her 4th infusion of re-tmt. Otherwise tmt was well tolerated. All pts had decline in circulating CD 19 positive B cells to < 0.03 X 109 and there were no significant decreases in IgG or IgM levels. The table below summarises the response to the various tmts with R. Overview of Response to Initial and Re-treatment with Rituximab Patient 1st Treatment 2nd Treatment DDR/R-CVP ♣ Median Plt. ct Response Median Plt Ct Response Median Plt. Ct Response ♣ 1 270 CR 319 CR 338 CR 2 102 CR 199 CR ♣ 3 157 CR 9 NR 24 NR 4 50 PR 34 PR 52 PR 5 ♣ 50 MR 20 MR ♣ 6 65 PR 25 PR 7 8 NR 25 NR 8 7 NR 15 NR ♣ 9 10 NR 10 NR 10 6 NR 10 NR 11 195 CR 165 CR 12 325 CR 285 CR 267 CR ♣ 13 180 CR 10 NR 14 21 NR 169 CR 15 290 CR 150 CR 16 219 CR 155 CR 17 157 CR 80 PR 18 540 CR 350 CR 19 63 PR 13 NR 20 245 CR 30 NR 21 58 PR 181 CR 22 72 PR 72 PR 23 88 PR 78 PR 24 450 CR 636 CR Among 15 pts on re-tmt with std dose R after ITP relapse, there were 7 complete responses (CR’s) (plt ct > 150,000/ul [150k] for 2 consecutive weeks) and 3 partial responses (PR’s) (plt ct between 50–150k for 2 consecutive weeks). Response to the 1st and 2nd std dose tmt courses was similar (n=15) but 3 pts (#3, 17 & 20 {see table}) with initial CR’s had limited to absent responses to re-tmt. No HAMA or HACA were detected in the 3 pts. With augmented R, there were 3 CR’s among 7 pts randomized to the DDR group (#2, 11, 12). All 3 pts also had CR’s with the 1st tmt. Among 7 pts randomized to the R-CVP group, 1 pt had CR (also had CR with 1st R), 1 had PR (#6) and 4 pts failed to respond altogether; 1 pt just started R-CVP. No pt who did not respond to initial std dose R, responded to either DDR or R-CVP (see figure). 4 pts received re-tmt with std dose R and then augmented R. At this time it does not seem that augmented R has provided additional benefit to these 4 or the other retreated pts. In conclusion, Rituximab re-tmt at std or double dose is well tolerated and generally produces similar response durations to initial R tmt in pts with relapsed chronic ITP. However 3/15 CR pts had no response to re-tmt. Augmented R, either as R-CVP or as DDR, did not provide any clear benefit to pts not responding initially to std R but may be superior to std dose R in some pts. R-CVP was less well tolerated than other regimens. Quality of Response: Comparision of Initial Treatment Vs Re-Treatment with DDR R-CVP Quality of Response: Comparision of Initial Treatment Vs Re-Treatment with DDR R-CVP