Venetoclax and azacytidine combination is an effective bridge to transplant strategy in relapsed/refractory acute myeloi
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LETTER TO THE EDITOR
Venetoclax and azacytidine combination is an effective bridge to transplant strategy in relapsed/refractory acute myeloid leukemia patients P. Zappasodi 1 & M. Brociner 2 & G. Merati 2 & M. E. Nizzoli 2 & E. Roncoroni 1 & E. Boveri 3 & C. Castagnola 1 & L. Arcaini 1,2 Received: 15 July 2020 / Accepted: 31 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Dear Editor, The prognosis of relapsed/refractory (R/R) acute myeloid leukemia (AML) is poor without transplant [1], and only a minority of patients reach a reduced tumor load enough to successfully undergo allogeneic stem cell transplantation (HSCT). Venetoclax, approved in untreated AML unfit patients, in combination with low-dose cytarabine and hypometilating agents [2, 3] demonstrated activity also in the R/R setting [4, 5] and heavily pre-treated patients [6, 7]. Based on these evidences, we report on 10 refractory patients treated with the combination of azacytidine and venetoclax (Aza-Ven) as bridge to HSCT. Nine refractory AML and 1 acute undifferentiated leukemia, AUL, having already selected an available hematopoietic stem cell donor, were authorized by the national authority responsible for drugs regulation in Italy (AIFA) to receive up to three cycles Aza-Ven, followed by HSCT if at least a clinical response was obtained. All patients had previously received standard anthracycline-based induction and salvage regimen containing fludarabine and high-dose cytarabine; two patients had also received allogeneic transplant. No patient had previously received hypometilants. After ramp up phase administered as previously shown [3], prophilactic posaconazole was given from day 4 only in the first month of treatment, considered at higher risk of infectious complication. Due to the strong CYP3A4 inhibition by posaconazole, venetoclax was reduced to 100 mg from day 4, then increased
* P. Zappasodi [email protected] 1
Division of Hematology, Fondazione IRCCS Policlinico San Matteo, V.le Golgi, 19, 27100 Pavia, Italy
2
Department of Molecular Medicine, University of Pavia, Pavia, Italy
3
Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
to 400 mg daily from the second cycle onwards; azacytidine was given at 75 mg/mq/day s.c. for 7 days per cycle. Patients’ characteristics are summarized in Table 1. Overall response was obtained in 6 out of 10 patients (ORR 60%), and among responders, 4 obtained CR (66%), 1 CRi (17%), and 1 MLFS (17%), and four patients did not respond. A significant clearance of bone marrow blasts was documented in 8 patients already after the first cycle of treatment. In 5 out of 6 responding cases, we observed after the first month of treatment a much lower marrow cellularity than normal, severe reduction of myeloid compartment with a prevalence of immature myeloid precursors, reflecting the incomplete hematological recovery observed in most cases, then evolving to CR after the following cycles. The achievement of the best response was generally fast, occur
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