Most Read Articles
Stephen Padilla, 12 Dec 2019
Transitioning from bortezomib- to ixazomib-based induction is feasible, tolerable and effective in the treatment of community patients with newly diagnosed multiple myeloma (NDMM), according to a study presented at the 61st Annual Meeting of the American Society of Hematology (ASH 2019).
6 days ago
At the recent National Haematology Expert Meeting 2019, a panel of experts was convened to discuss the role of targeted therapy in the management of haematological malignancies. Highlights of their lectures are summarised below.
Dr Margaret Shi, 6 days ago

Immunotherapy-chemotherapy combinations, immunotherapy doublets, and combinations of immunotherapy with novel targeted agents are emerging as strategies for management of metastatic urothelial carcinoma (mUC) in view of the limitations with chemotherapy and single-agent immunotherapy, said an expert at the Uro-Oncology Asia 2020 conference. 

Stephen Padilla, 13 Dec 2019
Debulking tumour with two cycles of obinutuzumab prior to initiating frontline venetoclax therapy is effective for patients with absolute lymphocyte count (ALC) >25 × 109/L and lymph nodes <5 cm, with a success rate of >98 percent, and the addition of bendamustine to this therapy improves debulking for those with nodes 5–10 cm, according to a study presented at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH 2019).

Oral arsenic trioxide-based induction and maintenance achieves 100% CR, 3-year LFS and 3-year OS in newly diagnosed APL

Natalia Reoutova
23 Aug 2019

A recent study involving 99 patients in Hong Kong demonstrated that arsenic trioxide (As2O3), used as part of induction and maintenance treatment for newly diagnosed acute promyelocytic leukaemia (APL), is safe and highly effective, achieving 100 percent complete response (CR), 3-year leukaemia-free survival (LFS) and 3-year overall survival (OS) rates. 

Sixty-two consecutive patients (24 men and 38 women; median age, 52 years) underwent induction with all-trans retinoic acid 45 mg/m2/day, oral As2O3 10 mg/day, and ascorbic acid 1 g/day (AAA regimen) for 6 weeks (patients younger than 70 years additionally received daunorubicin 50 mg/m2/d on days 1–3), followed by consolidation with two monthly cycles of daunorubicin (50 mg/m2/d on days 1–2) plus cytarabine (100 mg/m2/d on days 1–5) and AAA maintenance (given for 2 weeks every 8 weeks) for 2 years. [Cancer 2019;125:3001-3012]

However, not all newly diagnosed patients included in the study consented to oral As2O3 induction treatment. “It would be important to follow up these nonconsenting patients, as their outcomes might give useful comparative information,” wrote the researchers.

Therefore, a contemporaneous cohort of 37 newly diagnosed APL patients (15 men and 22 women; median age, 51 years) who did not consent to oral As2O3 induction received an otherwise identical induction, consolidation, and AAA maintenance, and served as a comparator group.

By day 28, CR was achieved morphologically and molecularly by all patients who received oral As2O3 induction. Both the LFS and OS rates were 100 percent at 3 years and 94.1 percent at 5 years.

The most common adverse events (AE) were haematologic. “Although thrombocytopenia occurred in 98.5 percent of cases, life-threatening bleeding was not observed because of vigorous haemostatic support,” noted the researchers.

The most common nonhaematologic AE was hepatotoxicity. Grade 3/4 transaminitis occurred in 25.8 percent of patients who received oral As2O3 induction. “Temporary withholding of drugs sufficed, and all patients were able to complete the intended treatment,” commented the researchers.

Compared with the same dose of intravenous (IV) As2O3, the oral formulation’s slow and prolonged intestinal absorption results in a lower peak plasma arsenic concentration, yet similar area-under-the-curve bioavailability. [Eur J Clin Pharmacol 2002;58:521-526] The lower plasma arsenic concentration achieved with oral As2O3 only has a minimal effect on QTc  and, in this study, none of the patients had a QTc >500 milliseconds. [Blood 2006;108:103-106] In contrast, QTc prolongation (>500 milliseconds) was reported in up to 65 percent of cases treated with IV As2O3. [J Clin Oncol 2014;32:3723-3728]

“The favourable tolerability and safety of oral As2O3 were evidenced by the absence of dropouts in our study, in contrast to dropout rates of 11–15 percent in some studies of IV As2O3,” wrote the researchers. [N Engl J Med 2013;369:111-121; Clin Oncol 2017;35:605-612; Blood 2010;116:3751-3757]

“None of the patients in the arsenic induction subgroup relapsed or died, whereas there were two relapses and one death in the non–arsenic induction subgroup,” wrote the researchers.

While the 5-year OS rates were comparable (100 percent in the As2O3 induction subgroup vs 96.9 percent in the non–As2O3 induction subgroup; p=0.21), the 5-year LFS rate with As2O3 induction was significantly superior vs non–As2O3 induction (100 percent vs 90.5 percent; p=0.03).

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Most Read Articles
Stephen Padilla, 12 Dec 2019
Transitioning from bortezomib- to ixazomib-based induction is feasible, tolerable and effective in the treatment of community patients with newly diagnosed multiple myeloma (NDMM), according to a study presented at the 61st Annual Meeting of the American Society of Hematology (ASH 2019).
6 days ago
At the recent National Haematology Expert Meeting 2019, a panel of experts was convened to discuss the role of targeted therapy in the management of haematological malignancies. Highlights of their lectures are summarised below.
Dr Margaret Shi, 6 days ago

Immunotherapy-chemotherapy combinations, immunotherapy doublets, and combinations of immunotherapy with novel targeted agents are emerging as strategies for management of metastatic urothelial carcinoma (mUC) in view of the limitations with chemotherapy and single-agent immunotherapy, said an expert at the Uro-Oncology Asia 2020 conference. 

Stephen Padilla, 13 Dec 2019
Debulking tumour with two cycles of obinutuzumab prior to initiating frontline venetoclax therapy is effective for patients with absolute lymphocyte count (ALC) >25 × 109/L and lymph nodes <5 cm, with a success rate of >98 percent, and the addition of bendamustine to this therapy improves debulking for those with nodes 5–10 cm, according to a study presented at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH 2019).