BACKGROUND Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. METHODS Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). RESULTS The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 non-hematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). CONCLUSIONS Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.)

• Lower GVHD after haploidentical transplant with posttransplant cyclophosphamide compared with HLA-matched unrelated donor transplant.• Comparable overall survival after haploidentical compared with matched unrelated donor transplant for AML.We studied adults with acute myeloid leukemia (AML) after haploidentical (n 5 192) and 8/8 HLA-matched unrelated donor (n 5 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P 5 .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P 5 .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P 5 .05) and 34% vs 52% (P 5 .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P 5 .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P 5 .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. (Blood. 2015;126(8):1033-1040

The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and MethodsPatients age 18 to 65 years with HCT comorbidity index # 4 and , 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLAmatched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. ResultsPlanned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P , .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, 20.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC (P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC (P , .01). ConclusionOS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

Haploidentical transplantation performed using T-cell-replete grafts and post-transplantation cyclophosphamide achieves outcomes equivalent to those of contemporaneous transplantation performed using MRDs and MUDs. Such transplantation represents a valid alternative for patients who lack a conventional donor.

BACKGROUND Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.)