A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.

Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.

Implementation of Systematic Financial Screening in an Outpatient Breast Oncology Setting.

Purpose: Implementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center.

Methods: We developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry.

Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab.

Purpose: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab.

Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia.

A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1).

Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial.

Background: The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m guadecitabine for 5 days as an effective treatment schedule.

Targeted alpha-particle immunotherapy for acute myeloid leukemia.

Because alpha-particles have a shorter range and a higher linear energy transfer (LET) compared with beta-particles, targeted alpha-particle immunotherapy offers the potential for more efficient tumor cell killing while sparing surrounding normal cells. To date, clinical studies of alpha-particle immunotherapy for acute myeloid leukemia (AML) have focused on the myeloid cell surface antigen CD33 as a target using the humanized monoclonal antibody lintuzumab. An initial phase I study demonstrated the safety, feasibility, and antileukemic effects of bismuth-213 ((213)Bi)-labeled lintuzumab.

International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia.

Purpose: Most patients with acute myeloid leukemia (AML) eventually experience relapse. Relapsed/refractory AML has a dismal prognosis and currently available treatment options are generally ineffective. The objective of this large, international, randomized clinical trial was to investigate the efficacy of elacytarabine, a novel elaidic acid ester of cytarabine, versus the investigator's choice of one of seven commonly used AML salvage regimens, including high-dose cytarabine, multiagent chemotherapy, hypomethylating agents, hydroxyurea, and supportive care.

Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death.

We hypothesized that the high early death rate (EDR) due to bleeding in acute promyelocytic leukemia (APL) is in part attributable to delays in all- trans retinoic acid (ATRA). We conducted a retrospective analysis of the timing of ATRA administration. 204 consecutive patients with newly diagnosed APL between 1992 and 2009 were identified.

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.

Adults with relapsed B cell acute lymphoblastic leukemia (B-ALL) have a dismal prognosis. Only those patients able to achieve a second remission with no minimal residual disease (MRD) have a hope for long-term survival in the context of a subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have treated five relapsed B-ALL subjects with autologous T cells expressing a CD19-specific CD28/CD3ζ second-generation dual-signaling chimeric antigen receptor (CAR) termed 19-28z.

Translocation t(11;17) in de novo myelodysplastic syndrome not associated with acute myeloid or acute promyelocytic leukemia.

Translocation t(11;17) is a well-recognized variant of acute promyelocytic leukemia (APL) and has also been identified in patients with mixed-lineage leukemia (MLL) non-APL acute myeloid leukemia. Here, we describe two patients bearing translocation t(11;17) presenting with a clinical diagnosis of de novo myelodysplastic syndrome (MDS): the first with sole karyotypic abnormality 46,XY,t(11;17)(p11.2; p13) and the second where it represented one of the two karyotypic abnormalities 46,XX,del(5)(q13q33)46,XX,del(5)(q13q33),t(11;17)(q24;q23).

Induction and postremission strategies in acute myeloid leukemia: state of the art and future directions.

Although the past decade has brought improvements in the treatment of AML, particularly for younger individuals, most patients succumb to the disease. With current induction therapy, most patients achieve remission, but the optimal strategy for post-remission therapy is unclear. Refinements to risk classification systems that incorporate additional molecular markers may better guide physicians in recommendations for postremission therapy.

Emerging new approaches for the treatment of acute promyelocytic leukemia.

The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death.

Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia.

Purpose: Lintuzumab (HuM195), a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest single-agent activity against acute myeloid leukemia (AML). To increase the potency of the antibody without the nonspecific cytotoxicity associated with β-emitters, the α-particle-emitting radionuclide bismuth-213 ((213)Bi) was conjugated to lintuzumab. This phase I/II trial was conducted to determine the maximum tolerated dose (MTD) and antileukemic effects of (213)Bi-lintuzumab, the first targeted α-emitter, after partially cytoreductive chemotherapy.