Intensive chemotherapy to improve outcome in patients with acute lymphoblastic leukemia over the age of 40: a phase II study for efficacy and feasibility by HOVON

Daenen, Simon; Holt, Bronno van der; Dekker, Ad W.; Willemze, R.; Rijneveld, Anita W.; Biemond, Bart J.; Muus, Petra; Loosdrecht, Arjan A. van de; Schouten, Harry C.; Kooy, Marinus van Marwijk; Breems, Dimitri; Demuynck, Hilde; Maertens, Johan; Wijermans, Pierre W.; Wittebol, Shulamiet; Klerk, E W de; Cornelissen, Jan J.

doi:10.1038/leu.2012.53

Cited by 21 publications

(14 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25, 26 For a minority of patients, allogeneic hematopoietic stem cell transplantation (HSCT) after myeloablative conditioning is potentially curative; however, this procedure is associated with frequent adverse events and significant treatment-related mortality. 25 For many patients with chronic-phase CML, targeted tyrosine kinase inhibitor therapy offers excellent disease control.…”

Section: Discussionmentioning

confidence: 99%

Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity

Batenchuk

Bœuf

Stubbert

et al. 2013

Blood Cancer Journal

View full text Add to dashboard Cite

Rhabdoviruses (RVs) are currently being pursued as anticancer therapeutics for various tumor types, notably leukemia. However, modest virion production and limited spread between noncontiguous circulating leukemic cells requires high-dose administration of RVs, which exceeds the maximum tolerable dose of the live virus. Furthermore, in severely immunosuppressed leukemic patients, the potential for uncontrolled live virus spread may compromise the safety of a live virus approach. We hypothesized that the barriers to oncolytic virotherapy in liquid tumors may be overcome by administration of high-dose non-replicating RVs. We have developed a method to produce unique high-titer bioactive yet non-replicating rhabdovirus-derived particles (NRRPs). This novel biopharmaceutical is multimodal possessing direct cytolytic and immunomodulatory activity against acute leukemia. We demonstrate that NRRP resistance in normal cells is mediated by intact antiviral defences including interferon (IFN). This data was substantiated using murine models of blast crisis. The translational promise of NRRPs was demonstrated in clinical samples obtained from patients with high-burden multidrug-resistant acute myeloid leukemia. This is the first successful attempt to eradicate disseminated cancer using a non-replicating virus-derived agent, representing a paradigm shift in our understanding of oncolytic virus-based therapies and their application toward the treatment of acute leukemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity

Batenchuk

Bœuf

Stubbert

et al. 2013

Blood Cancer Journal

View full text Add to dashboard Cite

show abstract

“…Previous studies of conventional chemotherapy consistently reported worse outcomes in older adults compared with younger patients, including lower remission rates, shorter RFS, and shorter OS . Worse outcomes have been attributed to poor prognostic factors at baseline and lower tolerability of chemotherapy in older patients .…”

Section: Discussionmentioning

confidence: 99%

Blinatumomab treatment of older adults with relapsed/refractory B‐precursor acute lymphoblastic leukemia: Results from 2 phase 2 studies

Kantarjian

Stein

Bargou

et al. 2016

Cancer

View full text Add to dashboard Cite

BACKGROUND: Older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) are reported to have a poor prognosis and few therapeutic options. In the current study, the authors evaluated treatment with single-agent blinatumomab in adults aged 65 years with r/r ALL. METHODS: A total of 261 adults with r/r ALL who were examined across two phase 2 studies received blinatumomab in cycles of 4-week continuous infusion and 2-week treatment-free intervals. The primary endpoint in each study was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first 2 cycles. Data were pooled and analyzed according to patient age at screening (aged 65 years vs aged <65 years). RESULTS: Of 36 older adults, 56% (95% confidence interval [95% CI], 38%-72%) achieved CR/CRh during the first 2 cycles compared with 46% (225 patients) (95% CI, 40%-53%) of younger adults. Complete minimal residual disease responses were 60% in older and 70% in younger responders. Three older responders (15%) and 61 younger responders (59%) proceeded to allogeneic hematopoietic stem cell transplantation. Kaplan-Meier curves overlapped for relapse-free and overall survival for both age groups. Older adults were found to have a similar incidence of grade 3 adverse events (AEs) as younger adults (86% vs 80%) but more grade 3 neurologic events (28% vs 13%). Cytokine release syndrome occurred in 7 older (19%) (1 case of grade 3) and 23 younger (10%) (4 cases of grade 3) adults. There were no treatment-related fatal AEs reported. CONCLUSIONS: Older adults with r/r ALL who were treated with single-agent blinatumomab were found to have similar hematologic response rates and incidence of grade 3 AEs compared with younger adults but had more neurologic events, which were reversible and primarily resolved with treatment interruption. Cancer 2016;122:2178-85.

show abstract

“…We also compared outcomes between patients that had a matched (6/6, A, B, DR) related donor (n 5 16) to those transplanted from a matched unrelated (MUD; n 5 19) or a mismatch unrelated donor (MMUD; n 5 5); MUD and MMUD were grouped together for this comparison because of the relatively small number of MMUD patients in this cohort and similar outcomes between these groups. While OS and DFS did not differ between groups, CIR at 3 years was significantly higher in the matched related donor group (50% [95% CI, 23 Table SVIIb).…”

Section: Research Articlementioning

confidence: 89%

“…We specifically looked at patients with 'high-risk' WBC counts at diagnosis ( 30 3 10 9 /L or 100 3 10 9 /L for B-or T-cell ALL, respectively) and those with MLL rearranged leukemia, characteristics that are associated with high relapse rates [23,31]. While numbers are small, our analysis suggests that these 'high-risk' patients do very poorly with postremission chemotherapy and that HSCT may abrogate some of the relapse risk.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports demonstrate that ALL patients with high risk features (generally defined as older age, high WBC at diagnosis or high risk cytogenetics) do not benefit from transplant as compared to patients without these features, due to a considerable NRM that offsets the lower relapse rate entailed with HSCT [9,22]. Accordingly we defined high-risk in this cohort as WBC count at diagnosis of 30 3 10 9 /L or 100 3 10 9 /L for Bor T-cell ALL, respectively or MLL rearranged leukemia [23].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Allogeneic transplantation is not superior to chemotherapy in most patients over 40 years of age with Philadelphia‐negative acute lymphoblastic leukemia in first remission

et al. 2016

View full text Add to dashboard Cite

Survival of patients 40 years of age with Philadelphia-negative acute lymphoblastic leukemia (ALL) remains poor with current therapeutic approaches. It is unknown whether allogeneic hematopoietic stem-cell transplantation (HSCT) in first remission confers a survival benefit compared to a chemotherapy-only approach. We retrospectively compared the outcome of patients >40 years treated with HSCT or chemotherapy alone in first remission (n 5 40 in each cohort). Three-year overall survival (OS) and diseasefree survival (DFS) were not significantly different between the chemotherapy-only and HSCT groups (OS, for the transplant group (CIR, P 5 0.011; NRM, P 5 0.014). Allogeneic transplantation for patients 40 years with Ph-negative ALL in first remission is associated with a lower CIR, but this benefit is offset by considerable NRM as compared with chemotherapy-only approach. HSCT may be beneficial in patients with high-risk disease features.

show abstract

Intensive chemotherapy to improve outcome in patients with acute lymphoblastic leukemia over the age of 40: a phase II study for efficacy and feasibility by HOVON

Cited by 21 publications

References 14 publications

Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity

Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity

Blinatumomab treatment of older adults with relapsed/refractory B‐precursor acute lymphoblastic leukemia: Results from 2 phase 2 studies

Allogeneic transplantation is not superior to chemotherapy in most patients over 40 years of age with Philadelphia‐negative acute lymphoblastic leukemia in first remission

Contact Info

Product

Resources

About