First Description of Upfront Target Therapy Treating AML and Bcll Presented Simultaneously As First Line
Authors: Carvalho Juliana Santos , Silva Anna Flávia Silva Alves , Silva Maysa Coité , Santos Itala Gomes , Aragão Laryssa Pinto , Lucas Larissa Ferreira , Santos Herbert Henrique de Melo , Botura Mônica , Rêgo Alex Nano Magalhães , Arruda Maria da Gloria B. , De Queiroz Crusoe Edvan , Almeida Alessandro de M. , Alves Renata , Lima Marianna Batista Vieira , Guimarães Victor Oliveira Sousa , Salvino Marco Aurelio 
Published: February 2021

INTRODUCTION: The occurrence of acute myeloid leukemia (AML) and chronic lymphoid leukemia (B-CLL) simultaneously is rarely described. We describe a case report of AML and B-CLL, diagnosed simultaneously, without any previous treatment for any of the hematological neoplasms [1]. The patient received low-dose cytarabine (ARA-C) and Venetoclax, which is medically indicated on label for both hematological neoplasms.

CASE REPORT: A 75-year-old male, presented with edema and joint pain one month before hospital admission, showing pancytopenia on a complete blood count and presence of blasts in peripheral blood. The patient was then referred to the hematology service.

The morphological analysis of the bone marrow aspirate showed 67.7% of myeloblasts, compatible with AML. Bone marrow immunophenotyping was performed, which identified 34.10% of myeloblasts, compatible with AML and 50.48% of monoclonal B lymphocytes (chronic B-cell lymphoproliferative disease). In flow cytometry there were two distinct populations of myeloblasts. Type 1 myeloblasts labeling CD7 +, CD13 +, CD34 ++, CD38 ++, CD45 ++, CD56 ++, CD117 ++, CD123 +, HLA-DR +++ and MPO + / ++. The second population marked CD13 + / ++, CD34 + / ++, CD38 ++, CD45 +, CD117 ++, CD123 +, HLA-DR ++ / +++ and MPO + (30%). Monoclonal lymphocytes showed CD11c + / ++ (70%), CD19 ++, CD20 + / ++ (84%), CD22 + (39%), CD23 + / ++, CD25 +, CD31 +/-, CD43 ++, CD45 ++ / +++, CD81 + (38%), CD200 + (85%) and Lambda +.

The molecular study was negative for genetic abnormalities: FLT3, KIT and NPM, configuring the patient as an intermediate risk for AML. In the cytogenetic analysis there was no growth of metaphases.

Patient received simultaneous diagnosis of AML and B-CLL. As he was ineligle to intensive chemotherapy (IC), we started original protocol Subcutaneous Cytarabin+venetoclax(VIALE C).

The patient had grade 2-3 AE(neutropenia managed with GCSF) ending the fourth cycle in July 2020.

The evolution of hematimetric parameters and diseases are described in graphics.

DISCUSSION: This is the first described case in our knowledge treated upfront with bcl2-inh target therapy for two absolutely different hematological neoplasms: AML and BCLL. Nowadays we are experiencing a new therapeutic model in oncohematology, in which the targeted therapy is gaining ground in relation to IC with excellent results. In this way, the importance of comprehension of the pathophysiological mechanism of the neoplasms and the way we can stop the disease proliferation is progressively guiding the new protocols.

Elderly patients are more likely to have early treatment-related death and exhibit therapeutic resistance, limiting alternatives. We decided to start first-line treatment with ARA-C and Venetoclax [2]. Venetoclax associated with ARA-C has a manageable safety profile, producing quick and durable remissions in elderly people with AML ineligible for IC, as well as in B CLL, being the best therapeutic alternative for the case, in our opinion. Venetoclax belongs to a group of drugs called Bcl-2 inhibitors, an anti-apoptotic protein, which works by blocking this protein in the body, causing apoptosis of both neoplastic cells.

The high rate of remission and low early mortality, combined with fast and durable remission, make Venetoclax and ARA-C a new and attractive treatment for the elderly [2].

In our case, the intention of the product in the first line was not B-CLL, but it would certainly be a good option for this profile of elderly patients.

CONCLUSION: We report the first description of simultaneous diagnosis of AML and B CLL treated with a Bcl-2 inhibitor, demonstrating that antitumor mechanisms can be extremely effective in completely different diseases.

We have a long way to go in the search for full knowledge of oncohematological diseases and targeted therapies. However, this case report shows that we are on the right track.

References:

1. MUSSAED, Eman Al; OSMAN, Hani; ELYAMANY, Ghaleb. Simultaneous existence of acute myeloid leukemia and chronic lymphocytic leukemia: a case report.Bmc Cancer.Springer Science and Business Media LLC. http://dx.doi.org/10.1186/s12885-016-2780-5.

2. WEI, Andrew H.; et al. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: results from a phase ib/ii study.Journal Of Clinical Oncology, [S.L.], 20 maio 2019. American Society of Clinical Oncology (ASCO). http://dx.doi.org/10.1200/jco.18.01600.

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Disclosures

De Queiroz Crusoe: Janssen:Research Funding.