Vincristine sulfate liposomes injection (VSLI) “bridging” to potentially curative hematopoietic stem cell transplantation (HSCT) in adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL).

Abstract

6527 Background: In a phase II, multi-national study (RALLY Trial; NCT00495079), 65 adults (median age 32 yrs, range 19 to 83) with Ph-ALL in second or greater relapse or who had progressed after two or more prior lines of treatment received single-agent, VSLI (Marqibo) 2.25 mg/m2 (without dose cap) IV weekly. All subjects were ineligible for immediate HSCT due to refractoriness to prior HSCT or the most recent salvage attempt, poor performance status, and/or insufficient anticipated lifespan. Methods: “Bridging” to HSCT was assessed as a pre-defined study secondary endpoint. Results: Overall response rate was 35% (95% CI: 24-48) with a 20% (95% CI: 11-32) complete response (CR) plus CR with incomplete hematologic recovery (CRi) rate. VSLI, despite delivering individual (2.8-5.5 mg) and cumulative (up to 70.1 mg) dose-intense VCR, had a similar safety profile to that reported for standard VCR. VSLI enabled bridging to HSCT in 11 of 65 (17%) subjects. Seven of the 11 (64%) subjects had undergone at least one pre-VSLI HSCT. Five of the 11 subjects were in CR/CRi at the time of post-VSLI HSCT. Three of 11 subjects remain alive at greater than 28, 33, and 35 mos, respectively, after post-VSLI HSCT. Five of 11 subjects relapsed and died following post-VSLI HSCT. Three of 11 subjects died of HSCT-related complications. All 11 subjects lived for greater than 100 days after post-VSLI HSCT. Conclusions: VSLI produced rapid CR/CRi or disease stabilization and a meaningful “bridge” to HSCT in 11 of 65 (17%) heavily pre-treated near end-stage adults with ALL. Long-term survival (greater than 12 mos) was achieved in 27% of those able to receive post-VSLI HSCT. These unexpected outcomes that are important to patients may reflect the effectiveness of the dose intensification facilitated by VSLI compared to that provided by standard VCR. Post-VSLI HSCT subject characteristic CR/CRi, N = 5 median (range) Non-CR/CRi, N = 6 median (range) Interval from 1st VSLI to HSCT, mos 2.7 (1.5-3.2) 5.0 (2.2-9.0) Cumulative VSLI exposure, mg 30.3 (15.8-41.4) 26.8 (4.0-49.0) OS following 1st VSLI, mos 8.6 (5.3-27.7+) 9.0 (6.3-34.9+)