Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody that targets B lymphocytes in early stages of development, successfully inducing remission in patients with relapsed acute lymphoblastic leukemia (ALL). We report our experience of 26 patients who were treated with IO followed by allogeneic stem cell transplantation (SCT). Background No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin that targets B lymphocytes in early stages of development, successfully inducing remission in patients with multiply relapsed ALL. Methods We describe our findings in 26 patients who received allogeneic hematopoietic stem cell transplantation (SCT) after treatment with IO between September 2010 and October 2011. Results Patients with a median age of 33 years (range, 5-70 years) received an allogeneic matched sibling donor (n = 9), matched- or 1-antigen mismatched unrelated donor (n = 16), or cord blood donor SCT (n = 1) while in complete remission (n = 23) or with active disease (n = 3). At the time of SCT, 15 patients were in complete remission without evidence of minimal residual disease (MRD) measured by multiparameter flow cytometry. Patients were heavily pretreated, including 5 patients who had received previous allogeneic SCT. Patients received a median of 3 courses of IO (range, 1-5 courses) before SCT. Seven patients are alive at a median follow-up of 13 months (range, 5-16 months), with 1-year event-free and overall survival (OS) of 22% and 20%, respectively. Patients without MRD at time of SCT had a markedly better 1-year OS of 42%. The cumulative incidence of nonrelapse mortality (NRM) at 6 months and 1 year were 40% and 60%, respectively, with 5 deaths attributed to venoocclusive disease (VOD). Conclusions Treatment with IO allows more patients to undergo transplantation while in remission, with favorable overall survival in patients without MRD who undergo transplantation. Reduction in hepatic toxicity is needed to improve overall results.

Either Cy, mCVAD, or mCBAD can yield successful PBSC mobilization in patients with multiple myeloma undergoing auto-HCT.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and has a heterogeneous clinical course. Some patients experience an indolent disease course, which does not require treatment or affect their overall quality of life. Other patients present with symptomatic advanced disease that rapidly progresses and requires therapy. For these patients, chemotherapy is the mainstay of treatment and has undergone significant evolution in the past few decades. From alkylating agents to purine analogs, response rates have greatly improved with new chemotherapy regimens. The development of chemoimmunotherapy regimens has also transformed the treatment of CLL. This article will review front-line treatment options for CLL and discuss the updated National Comprehensive Cancer Network guidelines.

Cytomegalovirus reactivation is a common complication of allogeneic hematopoietic stem cell transplant. The use of pre-transplant valganciclovir during the conditioning regimen followed by preemptive therapy has been used in an attempt to reduce the rate of early cytomegalovirus reactivation, but efficacy data are lacking. In this retrospective study, we evaluated the impact of pre-transplant valganciclovir during the conditioning regimen followed by a preemptive approach on the rate of early cytomegalovirus reactivation through day 100. The rate of cytomegalovirus reactivation through day 100 was 41% in the no-valganciclovir group compared to 46% in the valganciclovir group (p = 0.4). Interestingly, median time to cytomegalovirus reactivation was earlier in the no-valganciclovir group compared to the valganciclovir group (26 vs. 34 days; p = 0.008) and there was a trend toward a higher rate of cytomegalovirus disease through day 100 in the no-valganciclovir group (0.7% valganciclovir vs. 4% no-valganciclovir; p = 0.1). Day 100 survival was similar between the groups (90% valganciclovir vs. 91% no-valganciclovir; p = 0.8). Although the time to cytomegalovirus reactivation is significantly longer in the valganciclovir group, this did not impact the rate of cytomegalovirus reactivation or survival by day 100 suggesting that other strategies need to be explored.

3102 No highly effective salvage therapy exists for patients with relapsed acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody attached to calicheamycin and targets B lymphocytes in early stages of development. A 56% overall response rate was noted in a Phase I study of single agent IO in patients with refractory ALL (Jabbour ASCO 2011), enabling subsequent transplant in remission in a relatively large number of patients. Of note, in the year prior to the availability of IO, we consulted on 13 patients will ALL beyond second remission and transplanted 5 (38%), and after the availability of IO, we consulted on 41 patients and transplanted 27 (67%). Methods: We describe our findings in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) following treatment with IO between June 2010 and May 2011. IO was administered at 1.8 mg/m2 IV every 3 weeks. Results: 19 patients with median age 32 years (range 5–60) received an allogeneic matched sibling (n=6), matched unrelated donor (n=8), mismatched unrelated donor (n=4), or cord blood HSCT (n=1) in complete remission (CR) (n=2), CR without platelet recovery (n=14), and active disease (n=3); 10 patients were MRD negative at time of HSCT as determined by multiparameter flow cytometry. Patients had received 2 (n=3), 3 (n=9), 4 (n=4), 5 (n=2), or 6 (n=1) lines of salvage therapy prior to HSCT, including 3 patients who had received a prior allogeneic HSCT; IO was the last agent in 17 patients (2 patients refractory to IO received other therapy prior to HSCT). Patients received 1 (n=1), 2 (n=9), 3 (n=6), 4 (n=2), or 5 (n=1) courses of IO a median of 35 days (range 18–69) prior to transplant conditioning with busulfan (Bu) and colafarabine (Clo) (n=8), BuClo+ thiotepa (TT) (n=4), fludarabine (Flu) and melphalan (Mel) (n=1), FluMelTT (n=3), or etoposide and total body irradiation (TBI) (n=3); GVHD prophylaxis was tacrolimus-based for all patients, with post-HSCT cyclophosphamide added for patients receiving mismatched unrelated donors. With a median follow-up of 3 months among surviving patients (0.6–8.2), overall and progression-free survival is 59% at 3 months. There were 11 deaths, 6 from relapse, 4 from multi-organ failure involving VOD, and 1 from pneumonia. Transient liver enzyme elevations were noted in all of the patients, with 26% (n=5) patients developing VOD. The development of VOD was associated with greater lines of prior therapy prior to HSCT (3–5 lines prior salvage therapy, including 2 patients who had a prior allo-HSCT) and more intense transplant conditioning regimens (4 of the 5 patients received BuCloTT or FluMelTT). Conclusions: IO is an effective salvage therapy in patients with advanced ALL, allowing more patients to receive HSCT with encouraging response rates. Longer follow-up is needed to more completely assess disease control. Using reduced intensity HSCT conditioning regimens and avoiding multiple lines of prior therapies may result in less hepatic toxicity. Disclosures: O'Brien: Pfizer: Consultancy. Kantarjian:Pfizer: Research Funding.