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) 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. | 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 | | | Overview of Response to Initial and Re-treatment with Rituximab 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. ![Figure][1] Quality of Response: Comparision of Initial Treatment Vs Re-Treatment with DDR R-CVP [1]: pending:yes