Stone, Richard M

PURPOSE Older patients with ALL receiving conventional chemotherapy have poor survival due to toxic death and relapse. We hypothesized that a chemotherapy-free, targeted regimen using the anti-CD22 antibody-calicheamicin conjugate inotuzumab ozogamicin followed by the bispecific anti-CD19/CD3 T-cell engager blinatumomab would reduce toxic death and yield high rates of prolonged remission and survival. METHODS Eligible patients were age 60 years and older with untreated, Philadelphia chromosome (Ph)–negative, CD22-positive, B-cell ALL. Patients received up to two cycles of inotuzumab ozogamicin followed by four or five cycles of blinatumomab with intrathecal methotrexate CNS prophylaxis. The primary end point was 1-year event-free survival (EFS). RESULTS The 33 eligible patients had a median age of 71 years (range, 60-84) and a median CD22 expression of 92% (range, 21%-100%). Eight (24%) had previous chemotherapy or radiation for other cancers, six for multiple myeloma. The composite complete remission rate was 85% after two cycles of inotuzumab ozogamicin and 97% by the end of two cycles of blinatumomab. At a median follow-up of 30 months, the 1-year EFS and overall survival were 75% (95% CI, 61 to 92) and 85% (95% CI, 73 to 98), respectively. EFS was shorter with lower CD22 expression or detectable measurable residual disease at any time point. CONCLUSION Inotuzumab ozogamicin then blinatumomab without maintenance chemotherapy in older patients with untreated, Ph-negative, CD22-positive, B-cell ALL yields a high remission rate and excellent EFS. Given the lack of standard, safe, and effective therapies in this population, the regimen should be considered a standard treatment option.

PURPOSE Representativeness in acute leukemia clinical research is essential for achieving health equity. The National Cancer Institute's mandate for Comprehensive Cancer Centers (CCCs) to define and assume responsibility for cancer control and treatment across a geographic catchment area provides an enforceable mechanism to target and potentially remediate participatory inequities. METHODS We examined enrollee characteristics across 15 Cancer and Leukemia Group B/Alliance cooperative group adult acute leukemia clinical trials (N = 3,734) from 1998 to 2013, including participation in optional companion biobanks. We determined enrollment odds by race-ethnicity for all participants adjusted for national incidence, and for those enrolled at CCCs adjusted for catchment area incidence. We modeled biobank participation by sociodemographics using logistic regression. RESULTS Non-Hispanic (NH)-White patients were more likely to be enrolled than NH-Black, NH-Asian, or Hispanic patients (odds ratio [OR], 0.75, 0.48, and 0.44, respectively; all P < .001), but less likely than NH-Native American patients (OR, 1.91; P < .001), adjusted for national incidence. Enrollment odds were lower for NH-Black, NH-Asian, and Hispanic patients at CCCs adjusted for catchment area incidence (OR, 0.57, 0.26, and 0.32, respectively; P < .001); differences were driven by overenrollment of NH-White patients from outside self-defined catchment areas (18.1% v 12.3%; χ2 P = .01) and by CCCs with less absolute enrollee diversity (rank sum P = .03). Among all enrollees, NH-White race-ethnicity and lower neighborhood deprivation correlated with biobank participation (OR, 1.81 and 1.45, respectively; P = .01 and .03). For CCC enrollees, the correlation of race-ethnicity with biobank participation was attenuated by a measure accounting for their site's degree of enrollment disparity but not neighborhood deprivation. CONCLUSION Acute leukemia clinical research disparities are substantial and driven by structural trial enrollment barriers at CCCs. Real-time CCC access and enrollment monitoring is needed to better align research participation with local populations.

PURPOSE Chemotherapy outcomes in older patients with Philadelphia (Ph) chromosome–negative B-acute lymphoblastic leukemia (ALL) are very poor. Here, we evaluated blinatumomab as induction and consolidation therapy followed by prednisone, vincristine, 6-mercaptopurine, and methotrexate (POMP) maintenance chemotherapy in this patient population. PATIENTS AND METHODS Patients were treated at National Clinical Trial Network sites. Eligibility criteria included age ≥ 65 years and newly diagnosed Ph chromosome–negative B-ALL. Patients received blinatumomab as induction for one-two cycles until attainment of response (complete remission (CR) and CR with incomplete count recovery). Patients then received three cycles of consolidation with blinatumomab followed by 18 months of POMP maintenance chemotherapy. Eight doses of intrathecal methotrexate were administered as central nervous system prophylaxis. RESULTS Twenty-nine eligible patients were enrolled. The median age was 75 years, and the median bone marrow blast count at diagnosis was 87%. Cytogenetic risk was poor in 10 patients (34%), and five of 14 patients (36%) tested had the Ph-like ALL gene signature. Nineteen patients (66%; 95% CI, 46 to 82) achieved CR. Kaplan-Meier 3-year disease-free survival and overall survival estimates were 37% (95% CI, 17 to 57) and 37% (95% CI, 20 to 55), respectively. CONCLUSION Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed Ph chromosome–negative B-ALL, including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.