Compassionate use of glasdegib in combination with low-dose cytarabine for relapsed, refractory acute myeloid leukemia o
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LETTER TO THE EDITOR
Compassionate use of glasdegib in combination with low-dose cytarabine for relapsed, refractory acute myeloid leukemia or high-risk myelodysplastic syndrome Márcio Tavares 1
&
Sérgio Chacim 1 & José Mário Mariz 1
Received: 5 September 2020 / Accepted: 28 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Dear Editor, Management of patients with relapsed, refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS) remains a challenge. For most patients, treatment options are limited, responses are inadequate, and patients should be considered for experimental therapies. Aberrant Hedgehog (Hh) pathway activation has been implicated in the maintenance of leukemic stem cells, emerging as a promising therapeutic target [1, 2]. In November 2018, the Hh pathway inhibitor glasdegib, in combination with low-dose cytarabine (LDAC), received Food and Drug Administration approval for the treatment of newly diagnosed AML in adults who are ineligible for intensive induction chemotherapy [2, 3]. Here, we report six adult patients with R/R AML or HR-MDS treated with glasdegib, obtained through a compassionate use program following authorization by the Portuguese regulatory agency (INFARMED), plus LDAC between May and December 2019 (Table 1). Glasdegib was given orally at a dose of 100 mg daily for 28 days, and LDAC was given subcutaneously at 20 mg/m2/day for 10 days per cycle, until progression or unacceptable toxicity. Median age was 66 years
* Márcio Tavares [email protected] Sérgio Chacim [email protected] José Mário Mariz [email protected] 1
Departamento de Onco-Hematologia, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
(56–67 years). Median duration of treatment was 60 days (27– 155 days). Two patients died of progressive disease 43 and 69 days after treatment initiation. Stable disease (SD) was observed in the remaining four patients after 2 months of treatment according to the International Working Group criteria. These patients discontinued treatment due to adverse events; three patients received best supportive care and patient no. 2 is currently being treated with azacitidine. The most common grade 3–4 adverse event was febrile neutropenia (n = 13); three other grade 3–4 nonhematologic toxicities were observed and included lower gastrointestinal hemorrhage (patient no 3), mucositis (patient no. 2), and hemorrhagic stroke (patient no 6). Treatment-related adverse events like alopecia, dysgeusia, muscle spasms, renal failure, and rash were not observed. With a median follow-up of 7 months (0.1– 15.1 months), two-thirds of the patients survived more than 6 months after treatment initiation. From our experience, most patients treated with glasdegib plus LDAC achieve a best response of stable disease; a similar finding has been observed with single-agent glasdegib [4]. However, the median overall survival compared favorably to those of
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