Minimal Residual Disease in Adults with Advanced Relapsed Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Treated with Marqibo® (vinCRIStine sulfate LIPOSOME injection)

Abstract Abstract 4805 Minimal residual disease (MRD) testing in acute lymphoblastic leukemia (ALL) has been primarily used in the frontline treatment setting following achievement of morphologic remission where absence of detectable disease (molecular remission) may predict for a more favorable outcome. Potential utility of post-induction MRD testing in the advanced, relapsed/refractory adult Philadelphia chromosome (Ph) negative ALL setting has not been reported. We assessed MRD in the pivotal Phase 2 RALLY Study (HBS407, NCT00495079) of weekly high-dose (2.25 mg/m2 without any dose cap) vincristine sulfate liposome injection (VSLI, Marqibo®) monotherapy in 65 patients with either B- or T-cell lineage, Ph-negative ALL in 2nd or greater relapse or that had progressed following 2 or more lines of prior anti-leukemia therapy. All patients were heavily pretreated, all had received prior standard vincristine (VCR), 48% had undergone a prior hematopoietic cell transplant, and 43% were refractory to their immediate prior line of therapy. The median bone marrow blast percentage at presentation was 82%. Complete response (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 13 (20%) patients based on principal investigator (PI) assessment (predefined primary endpoint) and in 11 (17%) patients as assessed by an independent response review committee (IRRC). Two patients assessed as CR/CRi by a PI were classified as bone marrow blast (BMB) responders (morphologic remission lacking neutrophil and platelet count recovery) by the IRRC. MRD data from the first bone marrow demonstrating VSLI-induced CR/CRi based on site-specific flow cytometry methodology were available in 12 of the 13 CR/CRi patients. Molecular remission was confirmed in 8 of 12 (67%) patients. Response and VSLI treatment details for the MRD-negative and MRD-positive groups are provided in the table MRD Negative N = 8 MRD Positive N = 4 PI Response Assessment CR 5 1 CRi 3 3 BMB Responder 0 0 IRRC Assessment CR 6 1 CRi 0 3 BMB Responder 2 0 Response Duration, Median (Range) 140 days (32–162) 87 days (35–210) Overall Survival, Median (Range) 230 days (121–321) 203 days (71–327) VSLI Doses, Median (Range) 9 (4–18) 5 (4–10) VSLI Exposure (mg of VCR), Median (Range) 35.9 (17.4–58.6) 20.1 (15.8–33.4) Most (83%) patients who achieved a CR were MRD-negative. Half of the CRi patients, based on PI assessment, were MRD-negative. Both of the BMB responders, based on IRRC assessment, were MRD-negative. Median response duration, overall survival, number of VSLI doses, and cumulative VSLI dose expressed as milligrams of VCR were larger in patients who were MRD-negative. VSLI monotherapy administered as a third-, fourth-, or fifth-line therapy in adults with advanced, relapsed/refractory Ph-negative ALL was able to induce morphologic remission in 13 of 65 (20%) of patients and molecular remission in 8 of 12 (67%) evaluable morphologic remissions. MRD negativity may result from greater VSLI exposure and may be associated with more favorable response durations. MRD assessment may help to determine remission status particularly in patients with morphologic remission and incomplete recovery of either (i.e., CRi) or both (i.e., BMB Response) the peripheral blood platelet count and neutrophil count secondary to extensive prior myelotoxic therapy. Disclosures: Goldberg: Eisai: Speakers Bureau. Silverman:Talon Therapeutics: Employment. Deitcher:Talon Therapeutics: Employment, Equity Ownership.