Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study

Ravandi, Farhad; Assi, Rita; Daver, Naval; Benton, Christopher B.; Kadia, Tapan M.; Thompson, Philip A.; Borthakur, Gautam; Alvarado, Yesid; Konopleva, Marina; Takahashi, Koichi; Kornblau, Steven M.; DiNardo, Courtney D.; Estrov, Zeev; Flores, Wilmer; Basu, Sreyashi; Allison, James P.; Sharma, Padmanee; Pierce, Sherry; Pike, Allison; Cortes, Jorge; Garcia‐Manero, Guillermo; Kantarjian, Hagop M.

doi:10.1016/s2352-3026(19)30114-0

Cited by 118 publications

(100 citation statements)

References 28 publications

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“…Top1 inhibitors’ camptothecin derivatives used are irinotecan (colorectal [ 169 ], pancreatic (in combination) [ 170 ], and small cell lung cancers (in clinical trials and in combination) [ 171 , 172 ]), and topotecan (ovarian [ 173 , 174 ], cervical [ 175 ], and small cell lung cancers [ 176 ]). Top2 anticancer drugs commonly used are from the anthracycline group such as doxorubicin (acute leukemia [ 177 ], lymphomas [ 178 ], sarcomas [ 179 , 180 ], and solid tumors [ 181 ]), epirubicin (breast cancer [ 182 ]), valrubicin (bladder cancer [ 183 ]), and idarubicin (acute myeloid leukemia [ 184 ]), from the anthracenedione classes: mitoxantron and pixantron (lymphoma, [ 185 , 186 , 187 ]), and from the epipodopodophyllotoxins group such as etoposide (testicular [ 188 ] and small cell lung cancers [ 189 ]) and teniposide (brain [ 190 ] and small cell lung [ 191 ] cancers, acute lymphocytic leukemia [ 192 ]). Only a few numbers of Top1 inhibitors are in clinical trials including the promising indenoisoquinoline derivatives LMP400 (Indotecan), LMP776 (Indimitecan) (phase I), and LMP744 examined in a phase I study on lymphoma in dogs [ 193 ].…”

Section: Future Strategies For Copper Complexes As Top Inhibitors mentioning

confidence: 99%

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Molinaro

Martoriati

Pélinski

et al. 2020

Cancers

119

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Organometallics, such as copper compounds, are cancer chemotherapeutics used alone or in combination with other drugs. One small group of copper complexes exerts an effective inhibitory action on topoisomerases, which participate in the regulation of DNA topology. Copper complexes inhibitors of topoisomerases 1 and 2 work by different molecular mechanisms, analyzed herein. They allow genesis of DNA breaks after the formation of a ternary complex, or act in a catalytic mode, often display DNA intercalative properties and ROS production, and sometimes display dual effects. These amplified actions have repercussions on the cell cycle checkpoints and death effectors. Copper complexes of topoisomerase inhibitors are analyzed in a broader synthetic view and in the context of cancer cell mutations. Finally, new emerging treatment aspects are depicted to encourage the expansion of this family of highly active anticancer drugs and to expend their use in clinical trials and future cancer therapy.

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Section: Future Strategies For Copper Complexes As Top Inhibitors mentioning

confidence: 99%

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Molinaro

Martoriati

Pélinski

et al. 2020

Cancers

119

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“…PD-1/PD-L1 related antitumor therapy had been improving outcomes for all kinds of malignant diseases. [ 7 – 40 , 53 , 54 ] Some of them had been used as the first line choice alone or combined with chemotherapy. [ 7 – 9 , 11 – 14 , 18 , 19 , 21 , 24 , 25 , 30 , 35 , 38 , 39 ] However, as the range of use expanded, the potential exposure to immune-related adverse events associated with these PD-1/PD-L1 inhibitors also increased.…”

Section: Discussionmentioning

confidence: 99%

The relationship between pneumonitis and programmed cell death-1/programmed cell death ligand 1 inhibitors among cancer patients

Xu¹,

Xiang

et al. 2020

Medicine

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Background: We put the meta-analysis into practice to reveal the relationship between the incidence risk of immune-related pneumonitis and the use of programmed cell death-1 (PD-1) and ligand 1 (PD-L1) inhibitors related pneumonitis in cancer patients. Method: The meta-analysis was put into practice according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Odds ratio (OR) was evaluated by random effect model. Results: After screening and eligibility assessment, 33 clinical trials involving 19,854 patients were selected and used for the final meta-analysis after selection criteria checked. Compared with chemotherapy, the use of PD-1/PD-L1 inhibitors alone increased the incidence risk of all-grade (OR = 4.29, 95% confidence interval: [2.97, 6.19], P < .00001) and grade 3 to 5 immune-related pneumonitis (OR = 3.53, 95% confidence interval: [2.04, 6.11], P < .00001). Similar trend could also be found when PD-1/PD-L1 inhibitors were prescribed alone or in combination with other anti-tumor therapies. Conclusion: Whether PD-1/PD-L1 inhibitors were used alone or combined with other antitumor drugs, the incidence risk of immune-related pneumonitis would be increased.

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“…Several trials explored the efficacy of immune checkpoint inhibitors when combined with other agents. Induction regimens with nivolumab, cytarabine and idarubicin was tested in a phase I/II single-arm study with 44 patients with newly diagnosed AML or high-risk MDS [76]. Nivolumab was administered on day 24 of chemotherapy and continued every 2 weeks for up to a year in responders.…”

Section: Immune Checkpoint Blockadementioning

confidence: 99%

Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development

Stanchina

Soong

Zheng-Lin

et al. 2020

Cancers

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Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy comprised of various cytogenetic and molecular abnormalities that has notoriously been difficult to treat with an overall poor prognosis. For decades, treatment options were limited to either intensive chemotherapy with anthracycline and cytarabine-based regimens (7 + 3) or lower intensity regimens including hypomethylating agents or low dose cytarabine, followed by either allogeneic stem cell transplant or consolidation chemotherapy. Fortunately, with the influx of rapidly evolving molecular technologies and new genetic understanding, the treatment landscape for AML has dramatically changed. Advances in the formulation and delivery of 7 + 3 with liposomal cytarabine and daunorubicin (Vyxeos) have improved overall survival in secondary AML. Increased understanding of the genetic underpinnings of AML has led to targeting actionable mutations such as FLT3, IDH1/2 and TP53, and BCL2 or hedgehog pathways in more frail populations. Antibody drug conjugates have resurfaced in the AML landscape and there have been numerous advances utilizing immunotherapies including immune checkpoint inhibitors, antibody-drug conjugates, bispecific T cell engager antibodies, chimeric antigen receptor (CAR)-T therapy and the development of AML vaccines. While there are dozens of ongoing studies and new drugs in the pipeline, this paper serves as a review of the advances achieved in the treatment of AML in the last several years and the most promising future avenues of advancement

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Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study

Cited by 118 publications

References 28 publications

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

The relationship between pneumonitis and programmed cell death-1/programmed cell death ligand 1 inhibitors among cancer patients

Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development

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