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Bringing Novel Therapies to More Patients with Hematologic Malignancies through the Blood Cancer Research Partnership (BCRP)

  • Advances in Hematologic Malignancies Issue 8, Spring 2018

    Matthew S. Davids, MD, MMSc

    The Dana-Farber Blood Cancer Research Partnership (BCRP) started in 2013 with the idea that although community oncology sites may have some experience participating in larger phase 3 cooperative group trials, they do not typically have the opportunity to open smaller, early-phase trials with novel agents early in their development. This limits patient access to novel therapies, particularly for those patients who do not live near a major academic medical center.

    The mission of the BCRP has been to develop innovative clinical trials to offer to patients in community sites nationwide, thereby broadening the ability of these patients to access cutting-edge therapies for hematologic malignancies. By partnering with community practices with existing experience in clinical research, the BCRP accelerates accrual of these trials, thereby allowing critical scientific questions to be addressed in a rapid and efficient fashion. Twelve geographically diverse BCRP sites are now open in 12 states across the country, and the program has been generously supported through a Therapy Accelerator Program (TAP) grant from the Leukemia & Lymphoma Society.

    Since its inception, the BCRP has opened about a dozen clinical trials, most of which are investigator-initiated and led by a Dana-Farber investigator. Studies have evaluated novel treatments in both frontline and relapsed/refractory populations, with nearly all common hematologic malignancies represented, and a particular strength in multiple myeloma and chronic lymphocytic leukemia. The co-principal investigators include Irene Ghobrial, MD, Robert Soiffer, MD, and Matthew Davids, MD, MMSc.

  • map of Blood Cancer Research Partnership participating sites


  • Clinical Trial Example

    One example of a clinical trial run through the BCRP is our phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT — a trial supported by the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP 9204, NCT01822509). We hypothesized that immune checkpoint blockade with the CTLA-4 blocking antibody ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. A total of 28 patients were enrolled and 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 clinical benefit.

    In the six patients treated in the 3 mg/kg dose cohort, minimal efficacy or safety issues were observed, so an additional 22 patients were recruited and received a dose of 10 mg/kg. In that group, 5 (23 percent) patients had a complete response, 2 (9 percent) had a partial response, and 6 (27 percent) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia (example in Figure 1) and 1 patient with the myelodysplastic syndrome. Four patients had a durable response for more than 1 year. Immune-related adverse events, including one death, were observed in 6 patients (21 percent), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14 percent). Our correlative laboratory studies found that the clinical responses were associated with in situ infiltration of cytotoxic CD8+ T cells (Figure 2), decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood.

    We concluded that ipilimumab is a feasible treatment option for patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. We published these results in the New England Journal of Medicine (Davids et al., N Engl J Med, 2016), and recently gave an oral presentation to provide updated data at the 2017 ASH Annual Meeting (Davids et al., abstract 275). We subsequently expanded the trial to evaluate the safety and efficacy of the PD-1 blocking antibody nivolumab in this same patient population, and accrual is ongoing.

    BCRP sites were major contributors to accrual of this trial, which allowed us to efficiently recruit a geographically diverse array of patients and allow several patients to enroll who were unable to travel to Boston. In addition to helping with patient access and speed of accrual, the ability to draw on the BCRP sites to increase the patient samples available for correlative laboratory studies has been another important advantage of opening trials in the consortium. The high-quality data produced over a relatively short period of time through BCRP studies are already helping to shift the paradigm of clinical trial collaboration in hematologic malignancies.

    We welcome inquiries about BCRP participation and trials for this continuously growing and evolving effort.

  • Clinical and Histopathological Responses to Ipilimumab in Patients with Leukemia Cutis

    Figure 1: Clinical and Histopathological Responses to Ipilimumab in Patients with Leukemia Cutis

  • Immunohistochemical Evidence of In Situ Leukemic Response to Ipilimumab

    Figure 2: Immunohistochemical Evidence of In Situ Leukemic Response to Ipilimumab (CD8+ T-cell with perforin granules stained in red, surrounding leukemic blasts)