Prognostic Factors for Outcome in Patients (pts) with Refractory and Relapsed Acute Lymphocytic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (IO), a CD22 Monoclonal Antibody

Abstract

Background:IO was found to be highly active in pts with refractory-relapsed ALL, with an overall response rate of 58% and a median survival of 6.3 months (mos). Identifying factors associated with different outcomes on IO therapy may help select patients for this treatment and advice of prognosis.Methods:A total of 89 pts treated with IO on previous studies were analyzed. IO was given at 1.3-1.8 mg/m2 IV x 1 every 3-4 weeks or weekly (0.8 mg/m2 Day 1, 0.5 mg/m2 Days 8 and 15) every 3-4 weeks. Pretreatment factors associated with achieving marrow complete response (CR) and with survival were analyzed using standard statistical methods.Results:Baseline characteristics of the 89 pts are summarized in Table 1. Overall, 17 pts (19%) achieved CR, 29 (33%) had CRp, and 6 pts (7%) had bone marrow CR with incomplete recovery (Cri). 5 pts (6%) died within 4 weeks of starting therapy. The ORR was 58%. The rate of cytogenetic CR by morphologic responses was as follows: 8 cytogenetic CR/10 morphologic CR (80%); 16 cytogenetic CR/22 morphologic CRp (73%); and 4 cytogenetic CR/4 morphologic CRi (100%). The median survival of patients with at least marrow CR was 9 mos versus 3.4 mos for those without marrow CR (p<0.001). By multivariate analysis, a high peripheral blood absolute blast count (ABC) and low platelet count were independently associated with a lower likelihood of achieving at least marrow CR. With a median follow-up of 23 mos, (5-44), the median overall survival of pts who received IO was 6 mos; the median survival was 5 mos with the single-dose schedule and 9.5 mos with the weekly schedule. The median remission duration was 12 mos (1-year rate, 48%) (Figure 1A). Baseline characteristics independently associated with worse survival included adverse cytogenetics [complex karyotype, translocation (4;11), translocation (9;22), abnormal chromosome 17], disease beyond first salvage, and high peripheral blood ABC. Pts with 0, 1-2 or 3 adverse factors had a median survival of 42+, 7.5, and 2.4 mos, respectively (Figure 1B). To assess the benefit of achieving a marrow CR, we repeated the multivariate survival analysis using a 6-week landmark that excluded 5 pts who died within 6 weeks. The median survival was 9.2 mos and 3.4 mos for patients with and without marrow CR (p<0.001). The multivariate analysis selected the achievement of response as independently associated with survival improvement [HR=0.5 (95% CI=0.28-0.89); p=0.02]. Disease with complex karyotype, translocation (4;11), translocation (9;22), and abnormal chromosome 17 [HR=2.9 (95% CI=1.29-6.62); p=0.009], and disease status beyond first Salvage regimen [HR=1.2 (95% CI=2.16-3.91); p=0.01] were independently associated with significant worse survival. Pts with 0, 1- 2 or 3 adverse factors had a median survival of 42+, 8, and 3 mos, respectively (Figure 1C).Conclusion:Our current analyses identified a subset of adult pts with ALL in whom outcome of therapy with IO can be differentially predicted.Table 1Patients’ characteristicsN (%)ParameterSingle-Dose, n=49Weekly, n=40Overall, n=89Age, year≤183 (6)3 (8)6 (7)≥6012 (24)13 (33)25 (28)ECOG, PS0-144 (90)36 (90)80 (90)≥25 (10)4 (10)9 (10)Salvage StatusS113 (27)16 (40)29 (33)>S136 (73)24 (60)60 (67)PB ABC, x 109/L<1.033 (67)25 (63)58 (65)≥1.016 (33)15 (38)31 (35)WBC, x 109/L<4.028 (57)17 (43)45 (51)4-1111 (22)16 (40)27 (30)>1110 (20)7 (18)17 (19)BM blasts, %<203 (6)8 (20)11 (12)20-4910 (20)8 (20)18 (20)50-698 (16)6 (15)14 (16)≥7028 (57)18 (45)46 (52)Platelets, x 109/L<10043 (88)28 (70)71 (80)≥1006 (12)12 (30)18 (20)KaryotypeDiploid8 (16)9 (23)17 (19)Ph-positive9 (18)8 (20)17 (19)Translocation (4;11)6 (12)3 (8)9 (10)Complex13 (27)11 (28)24 (27)Abnormal chromosome 176 (12)5 (13)11 (12)Other6 (12)4 (10)10 (11)Prior ASCT7 (14)2 (5)9 (10)Prior HCVAD regimen35 (71)32 (80)67 (75)CD22-positive, %≥9028 (57)31 (78)59 (66)70-8914 (29)7 (18)21 (24)50-697 (14)2 (5)9 (10) [Display omitted] [Display omitted] [Display omitted] DisclosuresKadia:GSK: Research Funding; ARIAD: Honoraria. Hagop:ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding.